Tumor-educated platelets (TEPs) have recently emerged as an important component of liquid biopsy, yet the clinical relevance in colorectal cancer (CRC) remains unclear. Here, we employed 10 machine learning algorithms to develop a stable, accurate TEP-related gene signature (TEPGS) to explore its links to tumor-associated macrophages (TAMs) and spatial platelet abundance. TEPGS correlated strongly with poor prognosis and outperformed 71 published gene signatures in predicting CRC overall survival. Multi-omics analysis displayed that high TEPGs were marked by increased TP53 mutations, copy number alterations, diminished immune features, enrichment of pro-tumor SPP1+/FCN1+ TAMs, and elevated spatial platelet abundance. Patients with high TEPGS exhibited resistance to immunotherapy but responded to a BRAF V600E inhibitor, while TEPGS showed tentative value for predicting cetuximab response and preliminary utility for bevacizumab. Functional assays confirmed ARPC1B as an oncogene. Our findings establish TEPGS as a valuable biomarker for prognostic stratification and tailored therapy selection in CRC.

[This corrects the article DOI: 10.1016/j.isci.2026.116229.].

PURPOSE:This study aimed to identify symptom clusters in survivors with nasopharyngeal carcinoma undergoing radiotherapy and to explore the interrelationships among these symptoms. Furthermore, it sought to identify core and bridge symptoms and to observe their changes over time. METHODS:A longitudinal study was conducted, recruiting 181 survivors newly diagnosed with nasopharyngeal carcinoma who were undergoing radiotherapy. Measurements were taken during weeks 1-6 of radiotherapy. Symptom assessment was conducted using the MD Anderson Symptom Assessment Scale - Head & Neck Module. Symptom network analysis was performed at each time point, and centrality metrics were analyzed to explore the interrelationships among symptoms. RESULTS:Four stable symptom clusters were identified, with fatigue, feeling of being distressed, feeling sad, and difficulty swallowing/chewing as central symptoms, and feeling sad, feeling of being distressed, fatigue, and vomiting as bridge symptoms. The stability of the symptom network across the six time points was acceptable. CONCLUSION:The symptom network results are crucial for developing future targeted symptom management interventions. Future research should focus on developing precise interventions targeting core and bridge symptoms to alleviate nasopharyngeal carcinoma survivors' symptom burden. IMPLICATIONS FOR CANCER SURVIVORS:For nasopharyngeal carcinoma survivors undergoing radiotherapy, implementing a dynamic symptom management strategy with tailored interventions for core and bridge symptoms enhances symptom management efficiency, thereby improving survivors' quality of life.

Introduction:Early diagnosis of Ewing sarcoma (ES) is critical for improving patient prognosis. However, the accurate diagnosis of ES remains challenging, underscoring the need for novel diagnostic biomarkers to enhance diagnostic precision and reliability. This study aimed to identify potential gene expression-based biomarkers for the diagnosis of ES. Methods:We selected the GSE17679, GSE45544, and GSE68776 datasets from the Gene Expression Omnibus (GEO) database. After correcting for batch effects, we combined ES and normal tissue samples from the GSE17679 and GSE45544 datasets to create a combined cohort. Two-thirds of both the tumor and normal samples from the combined cohort were randomly selected for the training cohort, while the remaining one-third served as the internal validation cohort. Additionally, the GSE68776 dataset was used for external validation. To identify key diagnostic genes, we applied three machine learning algorithms: least absolute shrinkage and selection operator (LASSO), support vector machine recursive feature elimination (SVM-RFE), and random forest (RF). Results:HOXC6 was identified as a key diagnostic biomarker for ES. It demonstrated strong diagnostic performance across all cohorts, with area under the curve (AUC) values of 0.956 (95% CI: 0.909-0.990) in the training cohort, 0.995 (95% CI: 0.977-1.000) in the internal validation cohort, and 0.966 (95% CI: 0.910-0.999) in the external validation cohort. Functional validation through HOXC6 knockdown in the RD-ES cell line revealed that its suppression significantly inhibited cell proliferation and migration. Furthermore, transcriptome sequencing suggested potential oncogenic mechanisms underlying HOXC6 function. Discussion:These findings highlight HOXC6 as a promising diagnostic biomarker for ES, demonstrating robust performance across multiple datasets. Additionally, its functional role suggests potential as a therapeutic target.

Radiotherapy for nasopharyngeal cancer (NPC) frequently induces malnutrition, which is a serious complication that adversely affects patients’ quality of life and prognosis. Although there are currently nutritional assessment procedures for such patients, their clinical effectiveness requires further investigation. This study aims to evaluate the impact of implementing an optimal nutritional assessment strategy on the nutritional management skills of nurses and patients and on the nutritional status of NPC patients undergoing radiotherapy. The project followed a three-phase approach. In the first phase, a systematic search and critical appraisal of evidence on nutritional management for NPC radiotherapy patients was conducted, yielding 17 best-practice items and 18 audit indicators. A baseline assessment of these indicators was subsequently performed in a radiotherapy ward between November 2024 and January 2025. The findings from this audit informed the second phase, where barriers and facilitators were analyzed using the Consolidated Framework for Implementation Research. This analysis led to the development of the 4 C Nutrition pathway as the core intervention strategy, which was implemented in the third phase from March to May 2025. The effectiveness was evaluated by comparing pre- and post-implementation data on audit compliance, knowledge levels of nurses, patients’ treatment adherence, and nutritional status indicators. Comparative analyses used paired or independent-sample t-tests for continuous variables and chi-square tests for categorical variables, with significance set at P < 0.05 (SPSS software, version 25.0). A total of 51 patients were included pre-implementation, compared to 52 post-implementation. Following evidence translation, the implementation rates of nurse review indicator increased overall from a range of 0

DNA N 6 -methyladenine (6mA) is an emerging epigenetic mark in the mammalian genome. ALKBH1 preferentially exhibits 6mA demethylase activity for single-stranded DNA (ssDNA) or bubbled/bulged DNA, but not for double-stranded DNA (dsDNA). Nevertheless, ALKBH1 significantly decreases the cellular 6mA level in genomic DNA, whose prevailing DNA conformation in living mammalian cells is dsDNA. Therefore, the demethylase activity of ALKBH1 toward 6mA in genomic DNA, especially dsDNA, remains largely debated. Here, we found that YTHDF3 increases the 6mA demethylase activity of ALKBH1 in genomic DNA with different conformations, including dsDNA. Compared with ALKBH1, YTHDF3 preferentially recognizes and binds to 6mA-modified DNA with different conformations. YTHDF3 recognizes 6mA in genomic DNA, and binds ALKBH1 to recruit it to sites near 6mA in genomic DNA, thereby facilitating the ALKBH1-mediated removal of 6mA in genomic dsDNA. In summary, YTHDF3 is a novel genomic DNA reader and guides ALKBH1 to remove 6mA in human genomic DNA.

8561 Background: Approved first-line therapies of PD-L1/PD-1 inhibitors plus chemotherapy conferred significant survival benefits for advanced squamous non-small cell lung cancer (sqNSCLC). However, the prognosis remains to be improved. The epidermal growth factor receptor (EGFR) is highly expressed in sqNSCLC and associated with a poor prognosis. This study aimed to compare the efficacy of HLX07, a novel humanized anti-EGFR antibody, plus serplulimab (anti-PD-1 antibody) ± chemo versus serplulimab plus chemo as first-line option for advanced sqNSCLC. Methods: This randomized, multicenter phase 2 study consisted of 4 parts that assessed varied combinations of HLX07 (at different doses), serplulimab, and chemotherapy. Part 3 evaluated the preliminary efficacy of the three-drug combination and is presented below. Patients with stage IIIB/IIIC or IV sqNSCLC that was not amenable to surgery or radiation therapy and high tumor expression of epidermal growth factor receptor (H score≥150) and no prior systemic therapy were randomized 1:1 to receive intravenous HLX07 at 800 mg (group A) or 1000 mg (group B), in combination with serplulimab (300 mg) and chemotherapy (carboplatin and nab-paclitaxel), once every three weeks. The primary endpoints were independent radiological review committee (IRRC)-assessed objective response rate (ORR) and progression-free survival (PFS) per RECIST 1.1. Results: As of 31 December 2024, 27 patients were enrolled and randomly assigned to group A (n=13) and group B (n=14) in part 3. 15 (55.6%) patients had metastatic disease. With a median follow-up of 16.0 months, IRRC-assessed confirmed ORR per RECIST 1.1 was 69.2% (95% CI 38.6–90.9) in group A and 71.4% (95% CI 41.9–91.6) in group B. Disease control rate was 92.3% (95% CI 64.0–99.8), and 100% (95% CI 76.8–100.0), respectively. Median PFS was 15.1 (95% CI 4.1–not available) months in group A and not reached in group B. The median overall survival and duration of response were not reached in either group as of the data cutoff date. All the patients in both groups reported treatment-emergent adverse events (TEAEs); most common TEAEs of any grade included neutrophil count decreased (92.3% vs. 71.4%), white blood cell count decreased (84.6% vs. 85.7%), anemia (84.6% vs. 78.6%), platelet count decreased (76.9% vs. 71.4%), hypokalemia (53.8% vs. 64.3%), rash (46.2% vs. 57.1%), alopecia and hypocalcemia (46.2% vs. 50.0% for each). 6 (46.2%) patients, and 8 (57.1%) in group A, and B reported immune-related adverse events, respectively. Conclusions: First-line HLX07 plus serplulimab and chemotherapy showed encouraging preliminary efficacy with a manageable safety profile in patients with advanced sqNSCLC which warrants further investigation. Clinical trial information: NCT04976647 .

Abstract Background. Delta-aminolevulinic acid dehydratase (δ-ALAD), as a key enzyme in hemoglobin production, have been reported to be an endogenous inhibitor of proteasomerecently. Abnormal ALAD expression was discovered in several forms of cancer, however, the role of ALAD in tumor progression remains unclear. Methods. ALAD mRNA expression were analyzed through GEPIA, UALCAN online and GEO database in primary solid tumors, respectively. Overall survival was estimated with Kaplan–Meier plotter database in these tumors. Differentially expressed genes regulated by ALAD were discovered with the LinkedOmics database in breast and lung cancer, and then the key genes were screened by hub gene analysis. Their biological function were analyzed by Gene Ontology (GO) terms analysis and Kyoto Encyclopedia of Genes and Genomes enrichment (KEGG) analysis. Gene set enrichment analysis (GSEA) and in vitro experiments were used to verify the role of ALAD in cell cycle and apoptosis. The correlation of ALAD expression with immune cell infiltration and biomarkers of immune cells were identified by TIMER database. Results. The results showed that ALAD mRNA expression were significantly downregulated in most of primary solid tumors. Low expression of ALAD predicts worse overall survival. 240 genes related to ALAD were discovered to participate in transcriptional regulation through functional analysis. 9 hub gene showed that it was mainly enriched in cytosol and ubiquitin-protein transferase activity using GO analysis. High expression of ALAD can induce cell cycle arrest and apoptosis according to GSEA analysis and in vitro flow cytometry analysis and annexin V staining. TIMER results showed that ALAD was significantly associated with immune cell infiltration. Conclusions. Our study demonstrated for the first time that ALAD is downregulated and low expression of ALAD is associated with worse OS in multiple solid tumors. Vitro experiment showed that ALAD high expression can suppress tumor cell cycle process and promote apoptosis in breast and lung cancer. Furthermore, we first time analyzed the tumor immune effect of ALAD in multiple solid tumors, and these findings support that ALAD is positively linked to immune cell infiltration. To sum up, it indicates that ALAD may be a valuable prognostic biomarker of solid tumors.

Objective:To explore the role of Huangqin Decoction in intestinal homeostasis maintenance and colon carcinogenesis based on "sterol regulatory element binding protein-1c (SREBP-1)-cholesterol metabolism regulatory T cell (Treg) differentiation."Methods:It was decided to utilize a total of 50 healthy Wistar rats for the study, 20 of which were chosen at random to serve as controls, and 30 of which were used to create an intestinal homeostasis imbalance model. It was determined whether or not the modeling was successful by killing 10 rats from each of the two groups. The remaining 10 rats in the normal group were then employed as the control group for the experiment. The random number table method was used to split the rats into two groups: the Huangqin Decoction (n = 10) and the Natural Recovery (n = 10) groups. For seven days, participants in the Huangqin Decoction group received the herb, whereas those in the natural healing group received normal saline. The relative density of SREBP1, the levels of cholesterol ester (CE), free cholesterol (FC), total cholesterol (TC), and Treg cells were detected and compared.Results:When compared to the control group, the relative density of SREBP1 increased significantly before administration in the Huangqin Decoction group and the natural recovery group, but decreased significantly after administration, with statistical significance (P < 0.05) in the Huangqin Decoction group and the natural recovery group; the Huangqin Decoction group and natural recovery group had significantly higher levels of CE, FC, and TC than the control group before to administration, and these levels increased significantly after administration. CE, FC, and TC levels in Huangqin Decoction and natural recovery groups were much lower than those in natural recovery groups, and the difference was statistically significant (P < 0.05), according to the results; Prior to administration, Treg cell levels in Huangqin Decoction group and the natural recovery group were significantly higher, and Treg cell levels in the Huangqin Decoction group and natural recovery group were significantly lower after administration; the decrease in the Huangqin Decoction group was significantly greater than that in natural recovery group. P < 0.05 indicated that the difference was significant.Conclusion:Using Huangqin Decoction, one may efficiently regulate SREBP1, cholesterol metabolism, and Treg cell development, all of which play an important role in maintaining intestinal stability and minimizing the incidence of colon cancer.

Background The cancer genome is commonly altered with thousands of structural rearrangements including insertions, deletions, translocation, inversions, duplications, and copy number variations. Thus, structural variant (SV) characterization plays a paramount role in cancer target identification, oncology diagnostics, and personalized medicine. As part of the SEQC2 Consortium effort, the present study established and evaluated a consensus SV call set using a breast cancer reference cell line and matched normal control derived from the same donor, which were used in our companion benchmarking studies as reference samples. Results We systematically investigated somatic SVs in the reference cancer cell line by comparing to a matched normal cell line using multiple NGS platforms including Illumina short-read, 10X Genomics linked reads, PacBio long reads, Oxford Nanopore long reads, and high-throughput chromosome conformation capture (Hi-C). We established a consensus SV call set of a total of 1788 SVs including 717 deletions, 230 duplications, 551 insertions, 133 inversions, 146 translocations, and 11 breakends for the reference cancer cell line. To independently evaluate and cross-validate the accuracy of our consensus SV call set, we used orthogonal methods including PCR-based validation, Affymetrix arrays, Bionano optical mapping, and identification of fusion genes detected from RNA-seq. We evaluated the strengths and weaknesses of each NGS technology for SV determination, and our findings provide an actionable guide to improve cancer genome SV detection sensitivity and accuracy. Conclusions A high-confidence consensus SV call set was established for the reference cancer cell line. A large subset of the variants identified was validated by multiple orthogonal methods.

Ovarian cancer is the eighth most commonly diagnosed cancer among women worldwide. Even with the development of novel drugs, nearly one-half of the patients with ovarian cancer die within five years of diagnosis. These situations indicate the need for novel therapeutic agents for ovarian cancer. Increasing evidence has shown that hypoxia-inducible factor-1α(HIF-1α) plays an important role in promoting malignant cell chemoresistance, tumour metastasis, angiogenesis, immunosuppression and intercellular interactions. The unique microenvironment, crosstalk and/or interaction between cells and other characteristics of ovarian cancer can influence therapeutic efficiency or promote the disease progression. Inhibition of the expression or activity of HIF-1α can directly or indirectly enhance the therapeutic responsiveness of tumour cells. Therefore, it is reasonable to consider HIF-1α as a potential therapeutic target for ovarian cancer. In this paper, we summarize the latest research on the role of HIF-1α and molecules which can inhibit HIF-1α expression directly or indirectly in ovarian cancer, and drug clinical trials about the HIF-1α inhibitors in ovarian cancer or other solid malignant tumours.

Abstract To detect the expression of interlerukin-22 (IL-22) and associated genes and to evaluate their relationship with clinicopathological features and prognosis in laryngeal squamous cell carcinoma (LSCC). The expression of IL-22 and associated genes were evaluated by immunohistochemistry and real time polymerase chain reaction in LSCC tissues from 30 patients and adjacent non-tumor tissues. A statistical analysis was implemented to assess the relationship among levels of expression, clinicopathological factors, and overall survival. The expression of IL-22 and interleukin 22 receptor 1 (IL-22R1) was mainly located in the cytoplasm, and the expression of LSCC was significantly higher than in controls. The expression of aryl hydrocarbon receptor and signal transducer and activator of transcription 3 distributed in the cell nucleus, which was significantly higher in LSCC than in controls. The expression of IL-22 and IL-22R1 was associated with metastasis of lymph node and clinical stage of LSCC. Overall survival of LSCC was significantly poorer with higher expression of IL-22 and IL-22R1 than in those with lower expression. The present research indicated that the increased level of IL-22 and IL-22R1 may be related to the pathogenesis and prognosis of LSCC. IL-22 may be the important biomarker, which need further research.

BACKGROUND:Chemotherapy with or without consolidation followed by autologous hematopoietic stem cell transplantation is the first-line treatment for mantle cell lymphoma. However, the effectiveness and safety of bortezomib-based chemotherapy for patients with mantle cell lymphoma is still uncertain.METHODS:In this systematic review, the electronic databases of Cochrane Central Register of Controlled Trials, EMBASE, and PUBMED will be searched from inception to May 1, 2020. Randomized controlled trials that assessed the effectiveness and safety of bortezomib in combination with chemotherapy for patients with mantle cell lymphoma will be included. The patient's important outcomes include overall survival, progression-free survival, overall response rate, quality of life, and serious adverse events (eg, grade III-IV peripheral neuropathy, neutropenia, and infection). All process of the study selection, data extraction, and methodology evaluation will be carried out by 2 authors independently. RevMan 5.3 software will be utilized for statistical analysis.RESULTS:This study will provide a detailed summary of latest evidence related to the effectiveness and safety of bortezomib in combination with chemotherapy in overall survival, progression-free survival, overall response rate, quality of life, and serious adverse events for patients with mantle cell lymphoma CONCLUSION:: The findings of this study may provide possible guidance for bortezomib in combination with chemotherapy for patients with mantle cell lymphoma.SYSTEMATIC REVIEW REGISTRATION:PROSPERO CRD 42020154938.

Epidermodysplasia verruciformis (EV) is a rare disease caused by human papillomavirus (HPV) infection. Part of skin lesions at the exposed site would become malignant, but few cases with squamous cell carcinoma (SCC) transformation at unexposed sites have been reported. In December 2016, one EV patient with squamous cell carcinoma transformation at unexposed sites (perianal region) were admitted and treated at our hospital. Here we reported the clinicopathological characteristics and our surgical management of the SCC skin lesion of this EV patient. We deem that once local malignant transformation occurs, early surgical resection should be performed, and skin without lesions at the unexposed sites should be selected as the donor site for skin graft or skin flap transplantation.