Background: Short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) is used for locally advanced rectal cancer (LARC). However, the pathological complete response (pCR) rate still hovers around 30%. Radiotherapy and immune checkpoint inhibitors have been shown to exert synergistic anticancer effects. This phase II randomized clinical trial aimed to evaluate the efficacy and safety of SCRT followed by capecitabine plus oxaliplatin (CAPOX) and tislelizumab versus SCRT followed by CAPOX alone in LARC. Methods: Patients initially diagnosed with clinical tumor stage 1 to 2, with node involvement and no distant metastasis (cT1-2N+M0) or clinical tumor stage 3 to 4, with any node status and no distant metastasis (cT3-4NanyM0) rectal adenocarcinoma were randomly assigned to receive SCRT (25 Gy in 5 fractions [25 Gy/5F]), followed by 4 cycles of CAPOX combined with tislelizumab (SCRT-TNT-ICI) or CAPOX alone (SCRT-TNT). After total mesorectal excision, 2 cycles of postoperative chemotherapy were administered according to the patient’s preference. The primary end point was the pCR rate, and secondary end points included major pathological response (tumor regression grade 0 or 1), 3-year progression-free survival, 3-year overall survival, and adverse events. Results: Between September 2021 and March 2024, 118 patients were randomized, of whom 111 started the allocated treatment, with 53 and 58 in SCRT-TNT-ICI and SCRT-TNT groups, respectively. Of those, 89 patients had surgical resection, including 45 in the SCRT-TNT-ICI group and 44 in the SCRT-TNT group. The pCR rate was 45.3% (95% confidence interval [CI], 31.5% to 59.8%) in the SCRT-TNT-ICI group compared to 27.6% (95% CI, 16.6% to 40.8%) in the SCRT-TNT group (odds ratio = 2.17; 95% CI, 0.99 to 4.79; P = 0.052). The major pathological response rates were 50.9% (95% CI, 36.6% to 65.2%) and 31.0% (95% CI, 19.5% to 44.6%), respectively (odds ratio = 2.31; 95% CI, 1.06 to 5.01; P = 0.033). During the neoadjuvant treatment period, the incidence of grade 3 to 4 adverse events was comparable between the SCRT-TNT-ICI and SCRT-TNT groups, with anemia being the most common in both groups. Conclusion: This phase II study provides preliminary evidence of promising tumor regression with SCRT-TNT combined with tislelizumab in LARC, warranting further validation in phase III trials. Trial registration: This trial was registered at clinicaltrials.gov (Identifier: NCT05086627).

Objective To explore the relationship between CD8 + tumor-infiltrating lymphocytes (TILs) in rectal cancer, mismatch repair (MMR) status, and patient prognosis. Methods A total of 414 paraffin-embedded tissue samples from patients with pathologically confirmed stage Ⅰ–Ⅲ rectal cancer were included in this study. Tissue microarrays (TMAs) with a thickness of 4 µm were prepared, and immunohistochemical staining was performed using a CD8 antibody to detect the expression of CD8-positive cells. MMR status was assessed using immunohistochemical markers (MSH2, MSH6, MLH1, PMS2). Results CD8 + TILs were expressed on T lymphocytes. Density was significantly associated with tumor invasion depth, lymph node metastasis, and MMR status (P < 0.05), but not with age, sex, surgery type, or tumor size (P > 0.05). Patients with high CD8 + TIL density and stable MMR status had longer overall and progression-free survival. Univariate and multivariate Cox analyses indicated low CD8 + TIL density and unstable MMR status as independent risk factors for poor prognosis. Conclusion CD8 + TIL density and MMR status may serve as combined prognostic biomarkers in rectal cancer, with higher density and stable MMR status linked to better outcomes and potential guidance for immunotherapy strategies.

Basal-type muscle-invasive bladder cancer (BMIBC) is characterized by aggressive metastasis and poor prognosis but lacks molecularly defined therapeutic targets. Through integrative analyses of clinical cohorts and BBN-induced mouse models, we identified KRT14 as a core oncogenic driver that orchestrates the KRT14-IGF2BP1 signaling axis to promote BMIBC progression and lung metastasis. Mechanistically, residues K294 and E295 within the KH2 domain of IGF2BP1 specifically recognize conserved residues D226 and E227 within the nuclear export signal of KRT14. This direct interaction facilitates IGF2BP1-mediated cytoplasmic trafficking and auto-stabilization of its own mRNA, establishing a positive feedback loop that amplifies IGF2BP1-targeted pro-invasive gene expression. Functional disruption of this axis suppressed primary tumor progression and lung metastasis in BMIBC models. Collectively, our findings define the KRT14-IGF2BP1 axis as a previously unrecognized, potentially targetable vulnerability in BMIBC, whose inhibition may limit aggressive disease progression and inform future therapeutic strategies.

Background: Total mesorectal excision (TME), first proposed by Heald in 1982, remains the standard surgical approach for rectal cancer. However, accurately and quickly identifying and separating the correct planes while avoiding damage to blood vessels, nerves, and ureters remains challenging in TME. This study aimed to develop an artificial intelligence recognition model for the different structures involved and to evaluate its performance through internal and external verifications. Methods: A database of pelvic autonomic nerves, arterial and venous identification, ureters, the Toldt fascia, and separation layer during TME surgery was established by retrospectively collecting intraoperative images and videos of patients with rectal cancer from January 2016 to April 2024. An overall identification and navigation model for TME surgery was established through steps such as image sketching, model training and evaluation, and clinical application. Results: A total of 6700 high-quality intraoperative images from 325 patients in the training group were collected for this study. After 1000 iterations, the current model was obtained. The parameters for the model, namely mean intersection over union, recall, precision, and F 1, were as follows: ureter (0.7086, 0.7601, 0.9128, and 0.8295), artery (0.8095, 0.8789, 0.9111, and 0.8947), vein (0.8114, 0.8599, 0.9350, and 0.8959), Toldt fascia (0.8985, 0.9532, 0.9400, and 0.9466), and separation layer (0.7281, 0.8191, 0.8676, and 0.8427). Conclusion: This study successfully established a comprehensive recognition model for TME surgery, in which different structures were recognized as different colors. The successful establishment of this model is expected to prevent intraoperative structural damage and promote TME surgery standardization.

To explore the associations of CD8⁺ tumor-infiltrating lymphocytes (TILs) and mismatch repair (MMR) status with prognosis in patients with rectal cancer. Methods: Formalin-fixed paraffin-embedded (FFPE) tissue specimens were collected from 414 patients with pathologically confirmed stage I–III rectal cancer. Tissue microarrays (TMAs) with a thickness of 4 μm were constructed. Immunohistochemistry (IHC) using anti-CD8 antibody was performed to detect CD8-positive cell expression. MMR status was evaluated via IHC markers including MSH2, MSH6, MLH1 and PMS2. CD8⁺ TILs were expressed in T lymphocytes. CD8⁺ TIL density was significantly correlated with tumor invasion depth, lymph node metastasis and MMR status (P<0.05), whereas no correlations were observed with age, sex, surgical approach or tumor size (P>0.05). Patients with high CD8⁺ TIL density and proficient MMR (pMMR) exhibited longer overall survival (OS) and progression-free survival (PFS). Univariate and multivariate Cox regression analyses demonstrated that low CD8⁺ TIL density and deficient MMR (dMMR) were independent adverse prognostic risk factors. The combination of CD8⁺ TIL density and MMR status may serve as a combined prognostic biomarker for rectal cancer. Higher CD8⁺ TIL density together with pMMR indicates superior patient prognosis, which can provide evidence for developing immunotherapy strategies.

Approximately 60% of colorectal cancer (CRC) patients exhibit TP53 mutations, which are strongly associated with tumor progression, chemotherapy resistance, and an unfavorable prognosis. However, targeting p53 has historically been challenging, and currently, there are no approved p53-based therapeutics for clinical use worldwide. In this study, we discovered that ubiquitin carboxyl terminal hydrolase L3 (UCHL3) plays a crucial role in high-level glycolysis, enhanced stem-like properties, and 5-fluorouracil (5-FU) chemoresistance in TP53-mutant CRC by exerting its deubiquitinating enzyme activity to stabilize α-enolase (ENO1) protein. Notably, we identified a newly Food and Drug Administration (FDA)-approved drug, pacritinib, that potently suppresses UCHL3 expression by blocking the janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway in TP53-mutant CRC. Furthermore, Pacritinib was demonstrated to effectively inhibit glycolysis and improve the sensitivity to 5-FU chemotherapy in TP53-mutant CRC. Our findings suggest that targeting the JAK2-STAT3-UCHL3-ENO1 axis is a promising strategy to suppress glycolysis and enhance the efficacy of 5-FU chemotherapy in TP53-mutant CRC. Pacritinib shows potential for clinical application in the treatment of TP53-mutant CRC.

Objective:To identify potential factors influencing the survival prognosis of locally advanced rectal cancer patients receiving neoadjuvant chemoradiotherapy. Methods:A retrospective study was conducted to collect data from January 2009 to December 2020 on 270 patients with locally advanced rectal cancer who were admitted to the Fourth Hospital of Hebei Medical University. The clinical data of patients before and after neoadjuvant chemoradiotherapy and postoperative treatment were compiled. The endpoints of the study were disease-free survival and overall survival of the patients. The univariate and multivariable regression analysis were used to identify factors that influence the patients' survival prognosis. Results:Univariate analysis showed that factors associated with good prognosis in neoadjuvant chemotherapy patients included age <65 years, CEA value ≤5ng/mL, lymphocyte count >1.5×109/L, normal albumin level, NLR ≤2.64, SII ≤683.16, PNI >49.23, tumor distance from the anal margin >5cm, tumor length ≤5cm, tumor invasion of the bowel wall ratio ≤50%, lower T stage and N stage, good tumor regression response, absence of KRAS gene mutation, and mismatch repair protein deficiency. And multivariate analysis showed that age (HR=0.385, P=0.007), NLR (HR=0.294, P=0.011), cT stage (HR=0.287, P<0.001), and tumor regression grade (HR=0.273, P<0.001) were significant factors influencing DFS in patients receiving neoadjuvant chemoradiotherapy. For OS, age (HR=0.497, P=0.035), cT stage (HR=0.387, P=0.001), and tumor regression grade (HR=0.307, P<0.001) were significant factors influencing OS in patients receiving neoadjuvant chemoradiotherapy. Conclusion:Age, cT stage, NLR, and tumor regression grade are significant factors influencing DFS and OS in patients with locally advanced rectal cancer. Younger age, lower cT stage, lower NLR value, and lower tumor regression grade are associated with better survival prognosis.

BACKGROUND:The upregulation of serpin family B member 5 (SERPINB5) has been linked to the progression of rectal cancer. However, the specific roles and underlying mechanisms of SERPINB5 in rectal cancer are not fully understood. AIM:To investigate the roles and mechanisms of SERPINB5 in rectal cancer. METHODS:SERPINB5 protein level in rectal cancer tissues and cell lines was measured through western blot analysis. SW480 cells were transfected with pcDNA-SERPINB5 or short-hairpin RNA targeting SERPINB5 (sh-SERPINB5). Cell proliferation, invasion, and apoptosis were then evaluated. The interaction between SERPINB5 and heat shock protein 90 alpha class A member 1 (HSP90AA1) was confirmed through a co-immunoprecipitation assay. Subsequently, pcDNA-HSP90AA1 or sh-HSP90AA1 was transfected into SW480 cells, and cell progression was then detected. Moreover, rescue experiments were used to investigate the effect of the SERPINB5/HSP90AA1 axis on rectal cancer progression. Additionally, sh-SERPINB5-transfected SW480 cells were implanted into nude mice, and xenograft tumor growth was then evaluated. RESULTS:SERPINB5 was prominently upregulated in rectal cancer tissues and cells. SERPINB5 overexpression increased SW480 cell proliferation and invasion while reducing apoptosis. In contrast, SERPINB5 knockdown had the opposite effects. Moreover, SERPINB5 could interact with HSP90AA1 and promote HSP90AA1 expression in SW480 cells. HSP90AA1 overexpression facilitated SW480 cell proliferation and invasion and restrained apoptosis. By contrast, HSP90AA1 knockdown suppressed cell progression. The upregulation of HSP90AA1 reversed the SERPINB5 silencing-mediated inhibition of SW480 cell progression. Additionally, SERPINB5 knockdown retarded the growth of rectal cancer tumors in vivo. CONCLUSION:SERPINB5 knockdown inhibited rectal cancer cell proliferation and invasion and retarded xenograft tumor growth by inhibiting HSP90AA1 expression.

Background:Lynch syndrome is the most common hereditary colorectal cancer (CRC) syndrome, accounting for 3-5% of all CRC cases. Situs inversus totalis (SIT) is a rare congenital malformation with an incidence of 1 in 8,000 to 1 in 25,000. The co-occurrence of Lynch syndrome and SIT is extremely uncommon. Immune checkpoint inhibitors (ICIs) have demonstrated significant efficacy in treating microsatellite instability-high/deficient mismatch repair (MSI-H/dMMR) CRC. Tumors associated with Lynch syndrome frequently exhibit MSI-H, providing a theoretical basis for ICI use. Case presentation:We report a case of bifocal colon cancer associated with Lynch syndrome and SIT. After seven cycles of sintilimab, the patient developed gastrointestinal perforation due to tumor regression, necessitating emergency surgery. The anatomical variations associated with SIT required the surgical team to adopt an alternative approach. Postoperatively, the patient continued sintilimab treatment for 2 years. In June 2024, he underwent a colostomy reversal and proximal colectomy. Pathological examination revealed a tumor regression grade (TRG) of 0, indicating complete pathological remission (pCR), with no recurrence or metastasis detected upon follow-up. Conclusions:The anatomical variations associated with SIT increase the complexity of surgical procedures. Advanced imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI) are essential for assessing fine anatomical details and facilitating surgery. ICIs are an effective treatment option for Lynch syndrome-associated CRC, as demonstrated in this case. Future studies should investigate the optimal timing of immunotherapy, combination treatment strategies, and methods to mitigate immune-related toxicities. Such research will help develop comprehensive and personalized treatment plans for Lynch syndrome-associated CRC.

High expression of Solute Carrier Family 11 Member 1(SLC11A1) leads to a poor prognosis in patients with CRC, while the specific role of SLC11A1 in CRC remains unreported. Therefore, this study mainly addressed the preliminary mechanism and specific role of SLC11A1 in CRC. The results showed that six subsequent genes were successfully screened by the line database, and the abnormal expression of SLC11A1 was the most obvious in colorectal cancer patients. Following phenotypic experiments demonstrated that SLC11A1 promoted proliferation, invasion and migration of colorectal cancer cells. SLC11A1 Is also able to downregulate Acyl-CoA Synthetase Long Chain Family Member 4 (ACSL 4), Cyclooxygenase-2 (COX2), NADPH Oxidase 1 (NOX1) and upregulate the expression levels of Hypoxia-Inducible Factor 1 (FIH1), Glutathione Peroxidase 1 (GPX1) protein, inhibit the expression levels of MDA and Fe2+ in colorectal cancer cells, and resist ferroptosis in colorectal cancer cells. SLC11A1 Overexpression can up-regulate the protein expression level of TGFβ1 (Transforming Growth Factor Beta 1), p-Smad 2 / 3, activate TGFβ1 signaling pathway activity, and promote colorectal cancer cell progression. In conclusion, we successfully demonstrated that SLC11A1 confers resistance to ferroptosis in colorectal cancer cells, providing a potential target for the clinical treatment of colorectal cancer.

Purpose:Colorectal cancer (CRC) is a prevalent cancer worldwide, with metastasis significantly contributing to its high mortality and poor prognosis. This study focuses on the impact of Alkaline Phosphatase, Placental (ALPP) on epithelial-mesenchymal transition (EMT) in colorectal cancer cells and its role in the Wnt/β-catenin signaling pathway. Patients and Methods:Differential ALPP expression was first interrogated in metastatic versus non-metastatic CRC samples from The Cancer Genome Atlas (TCGA-CRC) cohort. Functional validation was subsequently performed in vitro with HT29 and HCT116 cell lines engineered for ALPP overexpression or CRISPR/Cas9-mediated knockdown. Proliferation, migration and invasion were quantified by CCK-8, wound-healing and Transwell assays; EMT and Wnt/β-catenin signaling were assessed by Western blot. Results:Bioinformatics analysis revealed significantly different ALPP expression between metastatic and non-metastatic patients. In vitro experiments further revealed that ALPP overexpression drives proliferation, invasion, migration and, consequently, metastasis of HT29 and HCT116 colorectal cancer cells, whereas ALPP knockdown abolishes these EMT-dependent effects. Increased ALPP expression resulted in increased levels of N-Cadherin, Vimentin, and Snail proteins, along with a decrease in E-cadherin protein expression, in contrast to findings following ALPP knockdown. Furthermore, ALPP overexpression was also associated with Wnt/β-catenin signaling pathway activation. Conclusion:ALPP was found to act as an oncogenic factor in colorectal cancer cell lines HT29 and HCT116, stimulating cell proliferation and facilitating EMT. Abnormal activation of the Wnt/β-catenin signaling pathway was also found to be linked to increased ALPP expression.

Colorectal cancer is the third leading cause of cancer death worldwide. In China, the incidence and mortality of colorectal cancer are increasing, in which low rectal cancer is more common. Ultra-low rectal cancer refers to rectal cancer where the distance between the tumor and the anus is less than 5 cm, it accounts for about 70

195 Background: In patients with advanced colorectal cancer (CRC), the recommended second-line treatment following first-line therapy with oxaliplatin-based regimens is irinotecan-based therapy. Liposomal irinotecan, a novel formulation of traditional irinotecan, has demonstrated potential to enhance efficacy while minimizing toxicity. This study aims to investigate the efficacy and safety of liposomal irinotecan in combination with 5-FU/LV and bevacizumab as a second-line treatment option for metastatic CRC. Methods: This is a multi-center, single-arm, prospective, phase II study. Patients with metastatic CRC who received oxaliplatin-based chemotherapy as first-line treatment were enrolled to receive liposomal irinotecan + 5-fluorouracil + leucovorin + bevacizumab regimen until disease progression and/or unacceptable toxicity. The primary endpoint is objective response rate (ORR), secondary endpoints include disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results: A total of 50 patients were enrolled from Jan 2024 to Jul 2024 across 6 sites in China. The median age was 56.5 years (range: 30.0-76.0), with 58.0% male and 36.0% ECOG 0. Among the patients, 38.0% had left-sided colon cancer, 24.0% had right-sided colon cancer, and 38.0% had rectal cancer. As of Sept 14, 2024, 39 patients had at least one tumor assessment and 19 patients were still on treatment. ORR and DCR were 20.5% (8/39, 95% CI: 9.3%-36.5%) and 84.6% (33/39, 95% CI: 69.5%-94.1%), respectively. Eleven patients had disease progression and 5 patients died, and the median PFS and OS were not reached. The relative dose intensity of liposomal irinotecan and 5-fluorouracil were 92.8% (range: 23.6%-109.6%) and 89.5% (range: 13.3%-116.8%), respectively. During treatment, 43 (86.0%) patients had at least one adverse event (AE) and 24 (48.0%) had grade 3-4 AE. Most common (≥ 10%) grade 3-4 AEs were neutropenia (20.0%), leukocytopenia (16.0%) and diarrhea (10.0%). No unexpected toxicities observed in this study. Conclusions: These preliminary results reveled that liposomal irinotecan + 5-fluorouracil + leucovorin + bevacizumab after oxaliplatin-based treatment for metastatic CRC was well tolerated with encouraging clinical activity, which warrants further follow up. Clinical trial information: NCT06184698 .

Rectal cancer is one of the most widespread malignant tumors in the world, with the common treatment methods being surgery, chemotherapy, and radiotherapy. Due to its minimally invasive nature and associated rapid postoperative recovery, laparoscopic radical surgery has become one of the preferred options for treating rectal cancer. With the continuous advancement of surgical techniques and the integration of advanced technologies, especially the application of indocyanine green (ICG) fluorescence technology, the precision and efficiency of surgeries have been greatly improved, fundamentally changing the approach to complex operations. One of the most innovative advancements is the use of ICG fluorescence navigation, particularly in laparoscopic colorectal cancer surgery. This technology leverages the properties of ICG, a near-infrared fluorescent dye, to enhance the visualization of key anatomical structures during surgery. The application of ICG fluorescence technology in laparoscopic rectal cancer surgery is a significant breakthrough, providing surgeons with a novel approach for improving intraoperative decision-making. This study aimed to examine the clinical application of ICG fluorescence imaging technology in laparoscopic rectal cancer surgery. A patient with rectal cancer was selected, and ICG was injected before surgery. During the procedure, a laparoscopic fluorescence imaging system was used to observe fluorescence signals from the tumor and lymph node areas in real time. The fluorescence imaging results were compared with those of conventional imaging to assess the role of this technology in tumor resection and lymph node dissection. Postoperative pathological examination was conducted to verify the accuracy of the imaging results, and postoperative follow-up was carried out to further determine the clinical value of ICG fluorescence imaging in rectal cancer surgery. In addition, we developed a case report guide containing 13 components: title, keywords, abstract, introduction, patient information, clinical findings, timeline, diagnostic evaluation, treatment intervention, follow-up, results, discussion, patient perspectives, and informed consent. Considering our findings, we believe that ICG fluorescence navigation technology will play an increasingly important role in the surgical treatment of rectal cancer.

Background:The treatment of colorectal liver metastases (CRLM) continues to pose a significant clinical challenge, with surgical resection remaining the gold standard. However, the efficacy of combining thermal ablation (TA) with liver resection (LR) compared to LR alone in managing multifocal CRLM remains a topic of debate. This meta-analysis aims to compare the outcomes of combining TA and LR with LR alone in patients with multifocal CRLM. Methods:A comprehensive literature search was conducted across PubMed, EMBASE, Cochrane Library, and Web of Science up to December 2024. Studies that compared the combination of TA and LR with LR alone in patients with CRLM and reported at least 1-, 2-, or 3-year overall survival (OS) and/or disease-free survival (DFS) were included. Data were extracted and analyzed using random-effects or fixed-effects models, depending on the degree of heterogeneity. Sensitivity analysis and assessment of publication bias were performed to ensure the robustness of the findings. Results:Six retrospective cohort studies involving 3084 patients (1286 in the TA+LR group and 1798 in the LR group) were included. No significant differences were found in 1-, 2-, and 3-year OS between the TA+LR and LR groups. However, the TA+LR group exhibited worse DFS. Subgroup analysis revealed a more pronounced decline in DFS in non-European TA+LR cohorts compared to LR cohorts, potentially reflecting regional differences. Additionally, DFS was significantly lower in the radiofrequency ablation (RFA) subgroup compared to the microwave ablation (MWA) subgroup. Complication rates were comparable between the two groups. Sensitivity analysis confirmed the stability of the results, and no significant publication bias was detected. Conclusion:Combining thermal ablation with liver resection is a feasible liver-sparing approach for treating extensive CRLM, applicable through both laparoscopic and open surgical techniques. Combined resection and ablation should be considered as an alternative to resection alone for patients with multiple metastases. Systematic review registration:PROSPERO https://www.crd.york.ac.uk/prospero/, identifier CRD42024629343.

This study aimed to investigate the effectiveness of electroencephalographic (EEG) biofeedback therapy in reducing anxiety levels and improving overall well-being among patients diagnosed with rectal cancer. A randomised controlled trial was conducted with 150 patients with rectal cancer who were randomly assigned to either the intervention group (n = 75) or the control group (n = 75). The intervention group received 16 sessions of EEG biofeedback therapy over 8 weeks, whereas the control group received standard care. Anxiety levels were assessed using the State-Trait Anxiety Inventory at baseline, post-intervention, 3-month follow-up, 6-month follow-up and 12-month follow-up. Secondary outcomes, including quality of life, sleep quality, treatment adherence, cortisol levels and heart rate variability (HRV), were also evaluated. The intervention group showed significant reductions in state anxiety (p < 0.001) and trait anxiety (p < 0.001) compared with the control group at all post-intervention time points. Significant improvements were also observed in the intervention group for quality of life (p < 0.001), sleep quality (p < 0.001), treatment adherence (p < 0.001), cortisol levels (p < 0.01) and HRV (p < 0.01). The effects were maintained at the 12-month follow-up. Electroencephalographic biofeedback therapy is an effective non-pharmacological intervention for reducing anxiety levels and improving overall well-being in patients with rectal cancer. The findings suggest that incorporating EEG biofeedback therapy into the standard care of patients with rectal cancer may enhance their psychological well-being, quality of life, sleep quality, treatment adherence, physiological stress responses and autonomic function. Long-term benefits were observed, indicating the sustainability of the intervention’s effects. Further research is warranted to investigate the underlying mechanisms and potential applications of EEG biofeedback therapy in other cancer populations.

OBJECTIVE:To identify lipid metabolism associated biomarkers in colorectal cancer (CRC). METHODS:To refine our list of candidate genes, we utilized the Molecular Complex Detection (MCODE) plug-in within Cytoscape software and performed protein-protein interaction (PPI) network analysis to extract hub genes centrally located within the networks, which potentially possess important regulatory functions. Hub gene-associated miRNAs and transcription factors (TFs) were analyzed using miRNet. Immunohistochemical staining was employed to verify the expression levels of hub genes in clinical CRC tissues. Concurrently, cellular experiments were designed to explore the functional roles of the hub gene DHCR7 at the cellular level, providing scientific evidence for the precision treatment of CRC. RESULTS:A total of 9008 differentially expressed genes (DEGs) were identified between CRC and control samples. Gene Set Enrichment Analysis (GSEA) revealed that these DEGs were mainly enriched in biological processes such as myogenesis, adipogenesis, oxidative phosphorylation, and fatty acid metabolism. Using Weighted Gene Co-expression Network Analysis (WGCNA), we found that the pink and yellow modules were most significantly associated with CRC. Cytoscape analysis identified six hub genes (DHCR7, FABP4, FASN, FAXDC2, PTGIS, SLC27A6). Their diagnostic performance was verified in the external GSE23878 dataset. Clinical studies showed a downregulation trend in the expression of FAXDC2 and PTGIS in CRC tissue samples, while FASN and DHCR7 were up-regulated in colon cancer tissues. However, the expression trend of FABP4 was inconsistent with previous bioinformatics predictions. Further cellular experimental results demonstrated that DHCR7 knockdown significantly inhibited CRC cell proliferation and induced apoptosis, which strongly supported the previous bioinformatics analysis. CONCLUSION:Our research successfully identified six hub genes in CRC through a series of rigorous analyses and experimental validations. These findings provide important molecular basis for further investigation into the pathogenesis and progression of CRC.

Objective: To develop a prognostic prediction model for patients with colorectal cancer based on a peripheral blood cell composite score (PBCS) system. Methods: This retrospective observational study included patients who had primary colorectal cancer without distant metastasis, who did not undergo radiotherapy or chemotherapy before surgery, who did not receive leukocyte or platelet-raising therapy within 1 month before surgery, and whose postoperative pathology confirmed colorectal adenocarcinoma with complete tumor resection. Patients with severe anemia, infection, or hematologic diseases before surgery, as well as those with severe heart, lung, or other important organ diseases or concurrent malignant tumors, were excluded. In total, 1021 patients with colorectal cancer who underwent surgical treatment in the Department of Gastrointestinal Surgery of the Fourth Hospital of Hebei Medical University from April 2018 to April 2020 were retrospectively included as the training set (766 patients) and the internal validation set (255 patients). Additionally, using the same criteria, 215 patients with colorectal cancer who underwent surgical treatment in another treatment group from March 2015 to December 2020 were selected as the external validation set. The "surv_cutpoint" function in R software was used to analyze the optimal cut-off values of neutrophils, lymphocytes, and platelets, and a PBCS system was established based on the optimal cut-off values. The scoring rules of the PBCS system were as follows: Neutrophils and platelets below the optimal cut-off value = 1 point, otherwise 0 points; Lymphocytes above the optimal cut-off value = 1 point, otherwise 0 points. The scores of the three cell types were added together to obtain the PBCS. Univariate and multivariate Cox regression analyses were performed to explore the correlation between patients' clinicopathological features and prognosis, and a nomogram was constructed based on the Cox regression analysis to predict patients' prognosis. The accuracy of the nomogram prediction model was validated using the C-index, calibration curve, and decision curve analysis. Results: The optimal cut-off values for neutrophils, lymphocytes, and platelets were 4.40×109/L, 1.41×109/L, and 355×109/L, respectively. The patients were divided into high and low groups according to the optimal cut-off values of these cells. Survival curve analysis showed that a high lymphocyte count (training set: P=0.042, internal validation: P=0.010, external validation: P=0.029), low neutrophil count (training set: P=0.035, internal validation: P=0.001, external validation: P=0.024), and low platelet count (training set: P=0.041, internal validation: P=0.030, external validation: P=0.024) were associated with prolonged overall survival (OS), with statistically significant differences in all cases. Survival analysis of different PBCS groups showed that patients with a high PBCS had longer OS than those with a low PBCS (P<0.05). Univariate and multivariate Cox regression analysis results showed that aspirin use history, vascular thrombus, neural invasion, CA19-9, N stage, operation time, M stage, and PBCS were independent factors affecting OS (all P<0.05). The PBCS was also an independent factor affecting disease-specific survival (P<0.05), but not progression-free survival (P>0.05). The above independent risk or protective factors were included in R software to construct a nomogram for predicting OS. The C-index (0.873), calibration curve, and decision curve analysis (threshold probability: 0.0%-75.2%) all indicated that the nomogram prediction model had good predictive performance for OS. Conclusion: This study demonstrates that the PBCS constructed based on preoperative peripheral blood levels of neutrophils, lymphocytes, and platelets is an independent factor associated with the prognosis of patients with colorectal cancer. The nomogram model constructed based on this score system exhibits good predictive efficacy for the prognosis of these patients.

BACKGROUND Colorectal cancer (CRC) is the third most common cancer and a significant cause of cancer-related mortality globally. Resistance to chemotherapy, especially during CRC treatment, leads to reduced effectiveness of drugs and poor patient outcomes. Long noncoding RNAs (lncRNAs) have been implicated in various pathophysiological processes of tumor cells, including chemotherapy resistance, yet the roles of many lncRNAs in CRC remain unclear. AIM To identify and analyze the lncRNAs involved in oxaliplatin resistance in CRC and to understand the underlying molecular mechanisms influencing this resistance. METHODS Gene Expression Omnibus datasets GSE42387 and GSE30011 were reanalyzed to identify lncRNAs and mRNAs associated with oxaliplatin resistance. Various bioinformatics tools were employed to elucidate molecular mechanisms. The expression levels of lncRNAs and mRNAs were assessed via quantitative reverse transcription-polymerase chain reaction. Functional assays, including MTT, wound healing, and Transwell, were conducted to investigate the functional implications of lncRNA alterations. Interactions between lncRNAs and transcription factors were examined using RIP and luciferase reporter assays, while Western blotting was used to confirm downstream pathways. Additionally, a xenograft mouse model was utilized to study the in vivo effects of lncRNAs on chemotherapy resistance. RESULTS LncRNA prion protein testis specific (PRNT) was found to be upregulated in oxaliplatin-resistant CRC cell lines and negatively correlated with homeodomain interacting protein kinase 2 (HIPK2) expression. PRNT was demonstrated to sponge transcription factor zinc finger protein 184 (ZNF184), which in turn could regulate HIPK2 expression. Altered expression of PRNT influenced CRC cell sensitivity to oxaliplatin, with overexpression leading to decreased sensitivity and decreased expression reducing resistance. Both RIP and luciferase reporter assays indicated that ZNF184 and HIPK2 are targets of PRNT. The PRNT/ZNF184/HIPK2 axis was implicated in promoting CRC progression and oxaliplatin resistance both in vitro and in vivo . CONCLUSION The study concludes that PRNT is upregulated in oxaliplatin-resistant CRC cells and modulates the expression of HIPK2 by sponging ZNF184. This regulatory mechanism enhances CRC progression and resistance to oxaliplatin, positioning PRNT as a promising therapeutic target for CRC patients undergoing oxaliplatin-based chemotherapy.

Angiogenesis is associated with tumor progression, prognosis, and treatment effect. However, the angiogenesis' underlying mechanisms in the tumor microenvironment (TME) still remain unclear. Understanding the dynamic interactions between angiogenesis and TME in colon adenocarcinoma (COAD) is necessary. We downloaded the transcriptome data and corresponding clinical data of colon cancer patients from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases, respectively. We identified two distinct angiogenesis-related molecular subtypes (subtype A and subtype B) and assessed the clinical features, prognosis, and infiltrating immune cells of patients in the two subtypes. According to the prognostic differential genes, we defined two different gene clusters to further explore the correlation between angiogenesis and tumor heterogeneity. Then, we construct the prognostic risk scoring model angiogenesis-related gene (ARG-score) including seven genes (ARMCX2, latent transforming growth factor β binding protein 1, ADAM8, FABP4, CCL11, CXCL11, ITLN1) using Lasso-multivariate cox method. We analyzed the correlation between ARG-score and prognosis, clinicopathological features, TME, molecular feature, cancer stem cells (CSCs), and microsatellite instability (MSI) status. To assess the application value of ARG-score in clinical treatment, immunophenotype score was used to predict patients' immunotherapy response in colon cancer. We found the mutations of ARGs in TCGA-COAD dataset from genetic levels and discussed their expression patterns based on TCGA and GEO datasets. We observed important differences in clinicopathological features, prognosis, immune feature, molecular feature between the two molecular subgroups. Then, we established an ARG-score for predicting OS and validated its predictive capability. A high ARG-score characterized by higher transcription level of ARGs, suggested lower MSI-high (MSI-H), lower immune score, and worse clinical stage and survival outcome. Additionally, the ARG-score was remarkably related to the CSCs index and immunotherapy sensitivity. We found two new molecular subtypes and two gene clusters based on ARGs and established an ARG-score. Multilayered analysis revealed that ARGs were remarkably correlated to the heterogeneity of colon cancer patients and explained the process of tumorigenesis and progression better. The ARG-score can help us better assess patients' survival outcomes and provide guidance for individualized treatment.