Abstract Background Bevacizumab resistance severely limits long-term efficacy in metastatic colorectal cancer (CRC). This study aimed to develop and validate a bevacizumab resistance-associated gene signature for prognosis prediction and immune microenvironment characterization in CRC. Methods Two GEO datasets (GSE19862, GSE86582) with bevacizumab response data and TCGA-COAD/READ RNA-seq data were analyzed. Overlapping differentially expressed genes (DEGs) linked to both CRC progression and bevacizumab resistance were identified. An 8-gene signature (AXIN2, PSORS1C1, KRT74, SLC2A3, STIL, IL33, GALNT6, HSD11B2) was constructed via univariate Cox and LASSO-Cox regression. Results In the TCGA cohort, high-risk patients had shorter overall survival (OS; log-rank P < 0.0001). Time-dependent ROC yielded 1-year AUC = 0.638, 3-year AUC = 0.657, and 5-year AUC = 0.757. Multivariate Cox regression confirmed the risk score as an independent prognostic factor. External validation in GSE39582 (optimal cutoff = −1.49) replicated these findings: high-risk patients had inferior OS ( P = 0.0016) with acceptable 1/3/5-year AUCs and retained independent prognostic value (HR = 1.634, P = 0.00415). CIBERSORT and ESTIMATE analyses showed that the high-risk group was characterized by increased M2 macrophages and neutrophils, higher immune and stromal scores, and reduced activated memory CD4 + T cells, monocytes, and activated dendritic cells (all P < 0.05). GSEA highlighted enrichment of TNF-α/NF-κB, IL-6/JAK/STAT3, and immune checkpoint pathways in the high-risk group. AXIN2 (HR = 0.829, P = 0.032) was an independent protective factor, while PSORS1C1 (HR = 1.356, P = 0.048) was an independent risk factor. Conclusion The 8-gene bevacizumab resistance signature robustly predicts prognosis and reflects an immunosuppressive microenvironment closely linked to bevacizumab failure in CRC. These findings provide novel insights into immune-mediated resistance and support clinical risk stratification.

Patients with BRAF V600E-mutant metastatic colorectal cancer have poor prognosis, and the value of first-line targeted combination therapies remains uncertain. We evaluated the cost-effectiveness of encorafenib plus cetuximab with or without chemotherapy compared with standard chemotherapy, using clinical outcomes from a phase 3 randomized trial. A partitioned survival model with long-term extrapolation was applied to estimate lifetime costs and health outcomes from a United States payer perspective. Although both targeted regimens improved survival compared with standard chemotherapy, they were associated with substantially higher costs. Consequently, neither targeted strategy was cost-effective at commonly used willingness-to-pay thresholds under current pricing. These findings demonstrate that clinically meaningful survival gains may not translate into economic value in first-line settings. This study underscores the importance of incorporating economic evidence into early treatment adoption decisions and highlights the need for pricing approaches that better align costs with patient benefit.

BACKGROUND:Cancer survivors experience disproportionate burdens of health-related social needs (HRSNs), yet the mortality implications of cumulative HRSN burden remain poorly characterized. RESEARCH DESIGN AND METHODS:We analyzed 3643 adult cancer survivors from the 1999-2018 National Health and Nutrition Examination Survey. HRSNs burden was assessed based on eight indicators. Cox proportional hazard models were applied to estimate the associations between cumulative number of unmet HRSNs and all-cause, cardiovascular disease (CVD), and cancer mortality, reporting hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS:Over a median 85-month follow-up, 1304 (24.99%) participants died, including 433 from cancer and 334 from CVD. Compared to those with 0-1 unmet HRSN, HRs (95% CIs) for participants with 6-8 unmet HRSNs were 4.01 (2.89-5.58) for all-cause mortality, 2.34 (1.08-5.06) for CVD mortality, and 4.00 (2.41-6.64) for cancer mortality. Restricted cubic spline curves found no evidence of non-linear relationships between unmet HRSNs count and all-cause, CVD, and cancer mortality. Associations between HRSN burden and all-cause and cancer mortality were more pronounced in participants under 60 years of age. CONCLUSION:Cumulative HRSN burden is associated with mortality risk among cancer survivors, particularly younger adults. Routine HRSNs assessment should be integrated into survivorship care to identify high-risk patients.

Chemoresistance remains a major obstacle in colorectal cancer (CRC) treatment. In this study, we performed an integrative multi-omics analysis of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets, combined with machine learning approaches, to systematically investigate the UFMylation pathway in CRC. The E2 conjugating enzyme UFC1 was identified as a key determinant of chemotherapy sensitivity, with copy number amplification and elevated expression in tumors, particularly in chemotherapy-responsive patients. Single-cell transcriptomics revealed UFC1 enrichment in malignant epithelial cells, and its expression correlated with DNA damage response and apoptosis pathways. A LASSO-Cox risk model incorporating UFM1 pathway genes effectively stratified patient prognosis. Based on the UFC1 crystal structure, structure-based virtual screening was performed using TransformerCPI 2.0 against a million-scale compound libraries, followed by molecular docking, molecular dynamics simulations, and in vitro validation. The lead compound AK968 exhibited stable binding to UFC1 (ΔG = –25.07 kcal/mol), suppressed CRC cell proliferation, and synergistically enhanced 5-fluorouracil efficacy in a UFC1-dependent manner, with increased γ-H2AX foci formation indicating enhanced DNA damage accumulation. These findings identify UFC1 as a druggable effector of the UFMylation pathway in CRC chemotherapy stress and provide a framework integrating computational target identification, structure-based drug screening, and experimental validation for precision oncology.

BACKGROUND:For patients with initially unresectable colorectal liver metastases (IU-CRLM) who achieve resectability through conversion therapy, the choice between simultaneous and staged resection remains controversial. This pioneering prospective cohort study directly compares these approaches, offering critical insights into their safety and oncologic efficacy. MATERIALS AND METHODS:This multicenter prospective cohort study, conducted across three centers from January 2009 to June 2022 (median follow-up, 49.8 months), enrolled 366 patients with IU-CRLM who achieved resectability after conversion therapy. Patients underwent either simultaneous or staged resection of primary and metastatic lesions. Primary outcomes included postoperative complications (Clavien-Dindo ≥II and ≥III), relapse-free survival (RFS), liver-specific RFS, and overall survival (OS). RESULTS:Among 366 patients (229 staged, 137 simultaneous), staged resection showed lower overall complications (35.8% vs. 48.9%, P = 0.014) and major complications (14.8% vs. 24.1%, P = 0.027). Staged resection improved RFS [hazard ratio (HR) = 0.780, 95% confidence interval (CI) 0.623-0.977, P = 0.030] and liver-specific RFS (HR = 0.737, 95% CI 0.584-0.932, P = 0.011), with no significant OS difference (HR = 0.811, 95% CI 0.594-1.108, P = 0.188). Multivariable analysis confirmed staged resection's independent benefits for RFS (HR = 0.587, P = 0.001), liver-specific RFS (HR = 0.522, P < 0.001), and OS (HR = 0.529, P = 0.003). CONCLUSION:This study provides compelling evidence that staged resection is the safer and more effective surgical strategy for patients with IU-CRLM achieving resectability through conversion therapy. With significantly lower complication rates and improved survival outcomes, these findings strongly support the adoption of staged resection in clinical practice. Randomized controlled trials are essential to confirm these results and refine treatment guidelines.

PURPOSE:Sacituzumab tirumotecan (sac-TMT), a trop-2-targeted antibody-drug conjugate, has demonstrated significant clinical benefit in the OptiTROP-Breast01 trial for patients with advanced or metastatic triple-negative breast cancer (TNBC). This study evaluated the cost-effectiveness of sac-TMT compared with chemotherapy from the perspective of the Chinese healthcare system. METHODS:A partitioned survival model incorporating multiple survival extrapolation approaches was developed to estimate long-term clinical and economic outcomes. Survival data were reconstructed from the OptiTROP-Breast01 trial, while cost and utility inputs were derived from publicly databases and literature. Outcomes included life-years, quality-adjusted life-years (QALYs), total costs, and key economic endpoints: incremental cost-effectiveness ratio (ICER), incremental net health benefit (INHB), incremental net monetary benefit (INMB), and expected value of perfect information (EVPI). Sensitivity, scenario, and subgroup analyses were conducted to assess uncertainty. RESULTS:In the base-case analysis, sac-TMT yielded an additional 0.32 QALYs and 0.35 life-years compared with chemotherapy, with an incremental cost of $31815.17, resulting in an ICER of $98796.02 per QALY, exceeding the $40763.34 threshold in China. One-way sensitivity analysis identified the dose intensity, utility for PFS, patient weight, and price of sac-TMT as key drivers of ICER. Scenario analysis showed that reducing the drug price to 20 % of the current level would lower the ICER to $13319.46/QALY, with a 99.82 % probability of cost-effectiveness. EVPI was estimated at $33.69 per person. CONCLUSION:While sac-TMT offers survival benefits in metastatic TNBC, it is unlikely to be cost-effective at current pricing. Substantial price reductions and optimized use may improve its economic value and support reimbursement.

Cell-free DNA (cfDNA) containing cancer information has become a key biomarker for cancer liquid biopsy. Current next-generation sequencing (NGS) technology for cfDNA detection often fail to capture multiomics information, such as fragmentomics, epigenetics, and genetics, in a single assay. Recently, Oxford Nanopore Technologies (ONT) has demonstrated advantages in acquiring cfDNA’s multiomics data by a single sequencing run. In this review, we summarize the recent advancements in library preparation and bioinformatic analyses for cfDNA methylation, copy number variations (CNVs), as well as other biomarkers derived from cfDNA sequencing on the ONT platform. Furthermore, we highlight the latest research progress in the clinical applications of multi-dimensional cfDNA features and outline the future directions of nanopore cfDNA sequencing. Overall, this review updates the understanding of cfDNA detection using nanopore sequencing, providing valuable insights for studies of cfDNA in cancer.

Excess body weight (EBW) increases the risk of colorectal cancer (CRC) and is linked to lower colonoscopy compliance. Here, we extensively analyzed 981 metagenome samples from multiple cohorts to pinpoint the specific microbial signatures and their potential capability distinguishing EBW patients with CRC. The gut microbiome displayed considerable variations between EBW and lean CRC. We identify 44 and 37 distinct multi-kingdom microbial species differentiating CRC and controls in EBW and lean populations, respectively. Unique bacterial-fungal associations are also observed between EBW-CRC and lean-CRC. Our analysis revealed specific microbial functions in EBW-CRC, including D-Arginine and D-ornithine metabolism, and lipopolysaccharide biosynthesis. The best-performing classifier for EBW-CRC, comprising 12 bacterial and three fungal species, achieved an AUROC of 0.90, which was robustly validated across three independent cohorts (AUROC = 0.96, 0.94, and 0.80). Pathogenic microbial species, Anaerobutyricum hallii , Clostridioides difficile and Fusobacterium nucleatum , are EBW-CRC specific signatures. This work unearths the specific multi-kingdom microbial signatures for EBW-CRC and lean CRC, which may contribute to precision diagnosis and treatment of CRC.

3596 Background: The need for safe and effective therapies for untreated, BRAF V600E-mutated, unresectable locally advanced or metastatic colorectal cancer remains unmet. The purpose of this study was to compare the efficacy and safety of the VIC (Vemurafenib/Irinotecan/Cetuximab) regimen versus bevacizumab plus chemotherapy as first-line setting in Asian patients. Methods: In the single-center prospective cohort study, 78 untreated, BRAF V600E-mutant, locally advanced or metastatic CRC patients were enrolled. Every two weeks, the VIC regimen and bevacizumab plus doublet or triplet chemotherapy are administered. We evaluated the objective response rate (ORR), the disease control rate (DCR), and the conversion resection rate. In progression-free survival (PFS) and overall survival, the Kaplan-Meier method was utilized (OS). Results: In the evaluable population, 32 patients received VIC regimen and 35 patients received bevacizumab plus chemotherapy. The ORR and DCR in the VIC group were significantly higher than in the bevacizumab-therapy group (ORR: 68.8% versus 40.0%, P = 0.018; DCR: 100.0% versus 80.0%, P = 0.023). The VIC regimen was significantly superior to bevacizumab plus chemotherapy for PFS (median, 11.9 vs 7.9 months; hazard ratio [HR] = 0.48, 95% CI, 0.27-0.87; P = 0.012) and OS (median, 24.5 vs 14.4 months; HR = 0.36, 95% CI, 0.16-0.78; P = 0.007). In the VIC group, the conversion resection rate for liver metastases was 42.1% (8 of 19 patients), and for local CRC it was 66.7% (6 of 9 patients with initially unresectable local CRC). Rates of treatment-related adverse events of Grade 3 to 4 were 32.4% and 31.1% for the VIC regimen and bevacizumab plus chemotherapy, respectively. Conclusions: Among Asian patients with BRAF V600E-mutated advanced CRC, the VIC regimen was superior to bevacizumab plus chemotherapy in terms of tumor response and oncological survival, with a tolerable and manageable toxicity profile in the first-line setting. Clinical trial information: NCT05540951 .

BACKGROUND The incidence of colorectal cancer (CRC) has increased in recent decades, and ranks fourth among males and third among females in China. Surgical resection remains the most important treatment modality for curative intent in CRC. Several studies found that surgeon volumes and specialization appeared to be associated with improved overall survival (OS). Moreover, numerous reports have suggested that specialization and minimally invasive surgery have gained increased popularity in CRC surgery. However, few studies have specifically examined the role and long-term survival of all stage CRC in a real-world study. AIM To evaluate the effect of surgeon specialization on survival changes and minimally invasive surgery utilization in a real world study. METHODS A retrospective analysis on the association between surgeon specialization and OS between 2008 and 2013 in Zhongshan Hospital CRC database was performed. Standard demographic, clinicopathologic, surgical and follow-up data were obtained from the CRC database. Surgeon specialty was categorized as colorectal surgeon (CS) and general surgeon (GS). CRC patients who underwent primary surgical resection were enrolled. RESULTS A total of 5141 CRC patients who underwent primary surgical resection between 2008 and 2013 were evaluated, 1748 (34.0%) of these by CS. The percentage of minimally invasive procedures in the CS group showed an increasing trend. There was no benefit associated with surgeon specialization for stage I, II and IV patients. Surgeon specialization exhibited a significant association with OS solely among stage III patients, with 5-year OS rates of 76% and 67% for the CS and GS groups, respectively (P < 0.01). Further analyses found that surgeon specialization was significantly associated with survival only in stage III rectal patients, and the 5-year OS rate in the CS group and GS group was 80% and 67%, respectively (P < 0.01). CONCLUSION Surgeon specialization is associated with improved OS after primary surgery in stage III rectal patients. An appropriate surgical technique, perioperative program and adjuvant therapy may contribute to survival benefit in these patients.

BACKGROUND:For patients with initially unresectable colorectal liver metastasis (IU-CRLM) receiving conversion therapy, disease relapse after conversion hepatectomy is common. However, few studies have focused on the assessment and management of relapse following conversion hepatectomy for IU-CRLM.METHODS:In the retrospective cohort study, 255 patients with IU-CRLM received conversion therapy and underwent subsequent R0 resection. The treatment effects of repeated liver-directed treatment (RLDT) versus non-RLDT for liver relapse were examined. Survival analysis was evaluated with the use of Cox proportional hazards methods. The importance of RLDT was further confirmed in the propensity score matching (PSM) and subgroup analyses.RESULTS:The 5-year overall survival (OS) rate after conversion hepatectomy was 34.9%. Liver relapse was observed in 208 patients. Of these patients, 106 underwent RLDT (65 underwent repeated hepatectomy and the remainder underwent ablation treatment), while 102 received only palliative chemotherapy. The relapse patients who underwent RLDT had a significantly longer OS than those who did not (hazard ratio (HR): 0.382, 95% CI: 0.259-0.563; P<0.001). In a multivariable analysis, RLDT was independently associated to prolonged survival (HR: 0.309, 95%CI: 0.181-0.529; P<0.001). In the PSM and subgroup analyses, RLDT consistently showed evidence of prolonging OS significantly.CONCLUSION:For IU-CRLM patients with liver relapse following conversion hepatectomy, the RLDT is essential for cure and prolonged survival. To avoid missing the opportunity for RLDT, intensive disease surveillance should be proposed.

Background: Currently, no published studies have compared the short-term and long-term outcomes of robotic-assisted and open surgery for elderly patients (aged 65 years or older) with sigmoid colon and rectal cancer in China. Hence, our study was conducted to assess whether robotic-assisted surgery is superior to traditional approaches. Methods: A total of 208 patients who received either open resection (n ​= ​93) or robotic-assisted resection (n ​= ​115) between October 2010 and October 2014 were included in the study. We compared clinical characteristic variables and patient demographics between the two approaches and assessed short- and long-term outcomes. Results: Patient characteristics were not significantly different between the groups. First flatus postoperative days (P ​< .001), less time to liquid diet (P ​= ​.004), and shorter postoperative hospital stay (P ​= ​.046) were found in the robotic-assisted surgery group. The operation time was also more in the robotic-assisted surgery group (P ​= ​.03). The 3-year overall survival rate was 83.0% in the robotic-assisted surgery group and 78.0% in the open surgery group (P ​= ​.938). The 3-year disease free survival rate was 76.0% and 72.0% in the robotic-assisted surgery and open surgery groups, respectively (P ​= ​.817). No significant difference was found in the overall survival and disease-free survival between the two approaches. Conclusions: Robotic-assisted surgery is safe and feasible for elderly patients with sigmoid colon and rectal cancer and is associated with more operation time and faster recovery as compared to open surgery. No significant differences were found in 3-year survival outcomes between the two groups.

The tumor-derived factors involved in the expansion and accumulation of myeloid-derived suppressor cells (MDSCs) in metastatic dissemination of colorectal cancer (CRC) to the liver has not been studied. Immunohistochemistry was used to detect sphingosine-1-phosphate receptor 1 (S1PR1) and signal transducer and activator of transcription-3 (STAT3) in human colorectal tumors. IL-6 and interferon-γ were detected by enzyme-linked immunosorbent assay (ELISA). Tumor growth, invasion, and migration were evaluated by MTT, transwell, and wound healing assays, respectively. Subcutaneous tumor-bearing and CRC liver metastasis (CRLM) nude mouse models were constructed. The percentage of MDSCs was measured using multicolor flow cytometry. Western blot assay was used to evaluate S1PR1 and p-STAT3 expression in MDSCs after separation from the liver and tumor by magnetic antibody. T-cell suppression assay was detected by carboxyfluorescein succinimidyl ester (CFSE). Aberrant co-expressed S1PR1 and p-STAT3 was correlated with metachronous liver metastasis and poor prognosis in CRC. A mutual activation loop between S1PR1 and STAT3 can enhance CRC cell proliferation, migration, and invasion in vitro and in vivo. The expression of p-STAT3 and its downstream proteins can be regulated by S1PR1. p-STAT3 was the dependent signaling pathway of S1PR1 in the promotion of cell growth and liver metastasis in CRC. The level of IL-6 and the associated MDSCs stimulated by the S1PR1–STAT3 correlated with the number of liver metastatic nodes in the CRLM mouse models and patients. Increased CD14 + HLA-DR −/low MDSCs from CRLM patients inhibited autologous T-cell proliferation and predict poor prognosis. The S1PR1–STAT3–IL-6–MDSCs axis operates in both tumor cells and MDSCs involved in the promotion of growth and liver metastasis in CRC. MDSCs induced by S1PR1–STAT3 in CRC cells formed the premetastatic niche in the liver can promote organ-specific metastasis.

Many genes and mutations have been reported for colorectal cancer (CRC); however, very few have been associated with colorectal cancer liver metastasis (CRLM). We performed gene expression profiling experiments to identify genetic markers for CRLM and elucidate the molecular mechanisms. Microarray experiments were performed on CRC primary tumor samples with or without liver metastasis (LM) using the Affymetrix U133 plus 2.0 GeneChip Array. A new identified gene-scinderin (SCIN) was overexpressed with synchronous LM at both the RNA level evaluated with quantitative real-time PCR and protein level evaluated with immunohistochemistry and also with short overall survival analyzed with Kaplan-Meier method. With multivariate analysis indicated that SCIN served as an independent poor prognostic predictor for CRC patients. Disease-free survival was also significantly lower in SCIN overexpressing CRC patients with metachronous LM. In addition, SCIN knockdown significantly reduced cell proliferation, induced cell cycle arrest, and promoted the expression of some cell cycle apoptosis-related protein. Moreover, the DIAPH1, STAT3, CDK2, CDK4, and EGFR levels were downregulated, whereas CDKN2B and COL4A1 were upregulated in DLD-1-shSCIN cells by microarray analysis compared with DLD-1 shCon cells. These findings revealed that SCIN may serve as an important predictor of CRLM and poor outcome for CRC patients. SCIN may be a potential therapeutic target in human CRC. However, translation of its roles into clinical practice will require further investigation and additional experimental validation.

This study aimed to explore the prognostic impact of KRAS and BRAF mutations in patients who underwent simultaneous resection for synchronous colorectal liver metastases (SCRLMs) that were initially resectable. Clinicopathological and outcome data of 139 consecutive patients with SCRLMs who underwent resection between July 2003 and July 2013 was collected from our prospectively established SCRLM database. The KRAS and BRAF genotypes were evaluated in the primary cancer tissues by pyrosequencing. The prognostic value of KRAS and BRAF status was assessed by Kaplan-Meier and Cox regression analyses. KRAS and BRAF mutated in 28.8% and 7.2% of the patients with SCRLMs, respectively, but the genotypes did not significantly associate with any clinicopathologic characteristics. By Kaplan-Meier survival analysis, we found KRAS mutation was not significantly associated with short overall survival (OS) (P = 0.213), but was significantly correlated with short disease-free survival (DFS) (P = 0.041); BRAF mutation was significantly associated with both short OS and DFS (P = 0.001, P<0.001, respectively). Multivariate survival analysis showed KRAS mutation was an independent negative prognostic factor for DFS (P = 0.005) and BRAF mutation was an independent negative prognostic factor for OS and DFS (P = 0.001, P<0.001, respectively). KRAS and BRAF mutation similarly contributed to an adverse prognostic effect in patients who underwent simultaneous resection for SCRLMs that were initially resectable. These findings should suggest the use of KRAS and BRAF status in current practice as an important determinant for precision surgery for initially resectable SCRLMs.

PURPOSE In recent years, aberrant mRNA translational control has gained much attention as a critical player in the malignant process of tumors. Eukaryotic initiation factor 4E (eIF4E), by binding to the mRNA cap, can regulate specific protein synthesis, contributing to malignancy in human tumors. However, integrin β1 mediated chemoresistance under translational control remains unknown in colorectal cancer. PATIENTS AND METHODS The expression relationship between eIF4E and Integrin β1, along with their clinical significance was investigated in colorectal cancerous tissues of 118 cases using immunohistochemistry. Cell transfection techniques of small interfering RNA (siRNA) and cDNA expression plasmid were applied to investigate the molecular relationship of integrin β1 and eIF4E and their biological effects on 5FU resistance in SW480 and LoVo cell lines. RESULTS The expression of eIF4E and integrin β1 was positively correlated in colorectal cancer, and patients with high expressions of both markers tended to have a worse prognosis according to a Kaplan-Meier survival analysis. Integrin β1 could contribute to 5-fluorouracil (5FU) resistance in colorectal cancer cell lines. Moreover, the protein expression of β1 could be regulated by eIF4E, interestingly, without any change of mRNA expression level. Significantly, Hoechst/PI double staining and an MTT assay proved integrin β1 could contribute to cellular survival and 5FU resistance under translational control of eIF4E in these cells. CONCLUSION We conclude that integrin β1 mediated 5FU chemo resistance in colorectal cancer could be translationally regulated by eIF4E. Promisingly, targeting key molecules of this translational apparatus may provide an innovative therapeutic strategy for colorectal cancer.

BACKGROUND:Growing evidence suggests that miR-150 plays an inhibitory role in various types of cancer. However, the function and underlying mechanisms of miR-150 in triple-negative breast cancer (TNBC) remain unknown.PATIENTS AND METHODS:miR-150 expression was detected by qRT-PCR and ISH in TNBC tumor and adjacent normal breast tissues. miR-150 function was analyzed by wound healing and transwell assay in vitro and mouse lung metastasis model in vivo. mRNA microarray, qRT-PCR, western blotting and luciferase assay were used to identify the target gene of miR-150. HMGA2 over-expression plasmid was co-transfected with miR-150 to study the role of miR-150 through regulating HMGA2.RESULTS:We found that miR-150 was down-regulated in TNBC tumor tissues compared to corresponding adjacent, normal breast tissues, and was correlated with decreased lymph-node metastasis. Ectopic expression of miR-150 suppressed TNBC cell migration in vitro and metastasis in vivo. Mechanistic study revealed that miR-150 down-regulates HMGA2 by directly targeting its mRNA. Moreover, the suppression of cell migration caused by miR-150 is relieved by over-expression of HMGA2, suggesting that miR-150 inhibits migration of TNBC cells by down-regulating HMGA2.CONCLUSION:This work indicates that the miR-150/HMGA2 axis may serve as a treatment marker in TNBC.

Circulating cell-free DNA (cfDNA) has become a potential diagnostic and prognostic biomarker for colorectal cancer (CRC). In non-cancerous diseases, it has been confirmed that cfDNA can be recognized by Toll-like receptor 9 (TLR9), leading to a significant biological change. Nevertheless, the biological significance of cfDNA and its relationship with TLR9 in tumor malignancy is still unclear. Therefore, the purpose of this study is to explore the biological role of cfDNA in colorectal cancer (CRC). The expression of TLR9 was measured in different CRC cell lines and cancerous samples by RT-PCR or immunohistochemistry, which showed that high expression of TLR9 was significantly correlated with the tumor metastasis, advanced TNM stage and poor prognosis of patients. Then, cfDNA was obtained from fluorouracil (5FU)-induced apoptotic cancer cells in vitro and transfection techniques were used to transfect siRNA and cDNA plasmid for TLR9. Cancer cells were stimulated using isolated cfDNA fragments, and results showed that cfDNA could promote colorectal cancer cell proliferation via TLR9. Meanwhile, we demonstrated that the cfDNA binding to TLR9 could facilitate cell migration and invasion. Finally, we demonstrated that cfDNA initiated downstream TLR9-MyD88 signaling and induced robust release of chemokine interleukin 8 (IL-8), which helped to elucidate the mechanisms underlying these phenomena. Our data suggest that cancer cell-derived cfDNA contributes to cancer progression through activation of TLR9-MyD88 signaling and IL-8 secretion in CRC. These findings provide a novel perspective for understanding of tumor progression and provoke a potential therapeutic target for CRC treatment.

Previous studies on the prognostic impact of survivin expression in gastrointestinal (GI) cancer have yielded inconsistent results. This study was initiated to assess the relationship between survivin expression and overall survival (OS) or disease free survival (DFS) in GI cancer patients. We applied system literature searches on EMBASE, PubMed, Web of science, and the Cochrane library to conduct this up-to-date meta-analysis. Thirty studies with totally 3622 GI cancer patients were collected. The prevalence of high survivin expression in GI cancer was 0.57 (95% CI: 0.51-0.63). High survivin expression was significantly associated with shorter OS (HR 1.57, 95% CI: 1.42-1.74) and DFS (HR 1.38, 95% CI: 1.21-1.58). Subgroup analysis also showed significant association between high survivin expression and poorer OS or DFS in gastric cancer or colorectal cancer. In summary, our study indicated that high survivin expression was related to poor prognosis in GI cancer. Well-designed studies with large sample and more convincing data are needed to confirm our conclusion.

Robotic surgical system has been widely applied in sphincter-preserving surgery for low rectal cancer with the advantages of clear 3D images and stably flexile manipulation. Its application principle includes radical resection of tumor and complete preservation of function. The main operation procedures of robotic surgical system in sphincter-preserving surgery for low rectal cancer are as follows: (1) Anterior resection of low rectal cancer: It is safe and feasible and has obvious advantages in observation of pelvic nerves, dissociation of presacral and sacral side, and high rate of sphincter-preserving, while the improvement of postoperative recovery and long-term survival needs to be verified by further large sample researches. (2) Per anus intersphincteric resection (ISR): It is mainly applied in T1 and T2 stage tumors with 2 cm distance from tumor low margin to anal edge after dissociation of mesorectum. The greater difficulty of manipulation is found in ISR, while robotic surgical system can complete the intersphincteric resection by transabdominal approach, but anal function may be affected with the possibility of feces spillage at night, so robotic ISR is now still in exploration stage. (3) Transanal everted pull-through resection (Welch resection): Associated application of this operation is rarely reported at home and abroad. Our department has completed 51 robotic procedures of Welch resection till March 2017. Welch resection is successfully performed in all the patients. The short-term clinical outcomes are quite satisfactory and long-term survival is followed up. We think that this procedure is safe and feasible under the strict mastering of indications. Owing to special manipulation advantages of quickly precise dissociation, cutting and anastomosis in small pelvic space, when compared to laparoscopic surgery, robotic surgical system has higher sphincter-preserving rate for low rectal cancer, however, no other advantages are found. We believe that with the development of surgical instruments and ongoing of large sample studies, robotic surgical system will play a more important role in the treatment of low rectal cancer.