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Background: The optimal maintenance therapy for rat sarcoma (RAS) and v-raf murine sarcoma viral oncogene homolog B (BRAF) metastatic colorectal cancers (mCRCs) remains unclear. It is critical to evaluate the reliability of cetuximab-capecitabine (the observation group) relative to capecitabine alone (control group). Patients and Methods: In this retrospective analysis, patients with RAS and BRAF mCRC admitted to Huizhou Municipal Central Hospital, between January 2016 and October 2020 were enrolled and treated with cetuximab plus 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) as an initial therapy. Patients whose disease was controlled after at least six cycles of treatment were administered a maintenance therapy until disease progression. We also analyzed the prognosis of patients according to clinicopathological features. Altogether, 39 RAS and BRAF mCRC patients were recruited from January 2016 to October 2020, with 18 cases in the treatment group and 21 cases in the control group. The difference in baseline clinicopathological features between the two treatments is not obvious. Results: The median progression-free survival after maintenance treatment in observation group (9.5 months [95% confidence interval (CI) = 6.4–12.6]), was significantly better than the control group (7.3 months [95% CI = 5.8–8.8]). During maintenance treatment, there were no deaths caused by treatment-related adverse events, and the overall incidence of rash acne was different between the observation and control groups (p < 0.05). Most adverse events were mild and easily controlled. Primary tumor site, baseline carcinoembryonic antigen levels, and microsatellite instability status were independent prognostic factors. Conclusion: Maintenance therapy using cetuximab plus capecitabine improved survival in patients with mCRC and was well tolerated by patients. [ABSTRACT FROM AUTHOR]

The abnormal expression of protein tyrosine phosphatase nonreceptor type 6 (PTPN6) has been proved to be associated with the progression of colorectal cancer. However, its role in chemosensitivity and related molecular mechanism have not been clarified. It has been reported that PTPN6 was down‐regulated in colorectal cancer cells compared with the normal colorectal cells. To evaluate the effects of PTPN6 on the proliferation and survival of colorectal cancer cells, PTPN6 was overexpressed in colorectal cancer cells in the present study. We found that cell proliferation and viability were both decreased after overexpression of PTPN6. The IC50 of 5‐Fu against colorectal cells was also declined in PTPN6 transfected cells. And further, we verified that PTPN6 could down‐regulate the expression of P‐gp and MRP‐1. Moreover, SP1 was the target protein of PTPN6 predicated by ChIPBase software and confirmed through Co‐immunoprecipitation assay and it was negatively regulated by PTPN6. To further verify the effect of SP1 on chemoresistance, SP1 was overexpressed. SP1 overexpression enhanced the drug‐resistance to 5‐Fu and abrogated the effects of PTPN6 upregulation on 5‐Fu resistance. All the above changes were associated with the down‐regulation of proteins related to MAPK signalling pathway, such as phosphorylation of extracellular regulated protein kinases (ERK) and p38. In summary, PTPN6 promoted chemosensitivity of colorectal cancer cells by targeting SP1 and inhibiting the activation of MAPK signalling pathway. Significance of the study: It has been demonstrated that the abnormal expression of PTPN6 was related to the progression of colorectal cancer. However, the chemosensitivity of PTPN6 and its molecular mechanisms were still unclear. Here, we identified that PTPN6 was down‐regulated in colorectal cancer cells. Moreover, PTPN6 overexpression not only reduced cell proliferation and viability, but decreased the resistance of colorectal cells to 5‐Fu. In our research, we found that the SP1 was the target protein of PTPN6 and it was negatively regulated by PTPN6. In addition, SP1 could increase the resistance of colorectal cells to 5‐Fu. Molecular mechanism studies have shown that PTPN6 promoted the chemosensitivity of colorectal cancer cells by inhibiting the activation of MAPK signalling pathway. [ABSTRACT FROM AUTHOR]

Background: SLIT and NTRK-like protein 2 (SLITRK2) encodes a transmembrane protein that regulates neurite outgrowth. Some studies have demonstrated that SLITRK2 overexpressed in glioma. But the expression pattern, prognostic value and immunologic function of SLITRK2 in tumors remains unknown., Methods: The expression pattern of SLITRK2 among pan-cancers was examined through the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx). We analyzed the association between SLITRK2 expression level and tumor stage among pan-cancers. Kaplan-Meier survival analysis was utilized to investigate the prognostic relevance of SLITRK2 across 33 different types of cancers. Moreover, the correlations among SLITRK2 expression, immune cell infiltration, immunomodulatory related genes, tumor mutation burden (TMB), microsatellite instability (MSI) were evaluated. The relationship between SLITRK2 expression and crucial genes mutations was also illustrated. By using tissue microarray (TMA), the expression of SLITRK2 in 89 paired gastric cancer (GC) tissues was investigated., Results: Our study indicated that SLITRK2 expression varied across cancers. Elevated SLITRK2 expression was positively related to advanced tumor stage, poor overall survival (OS) and reduced disease-free survival (DFS). Bioinformatic analyses underscore SLITRK2's role in immune response, with its expression significantly tied to immune cell infiltration and marker expression. Based on TMA data, SLITRK2 expression level was positively associated with differentiation, lymph node metastasis, AJCC stage, TNM stage, and poor survival outcome in GC patients., Conclusion: Our findings provided that SLITRK2 may function as a biomarker by regulating immune cell infiltration. In addition, we verified that high SLITRK2 expression was correlated with poor prognosis in GC., Competing Interests: Declarations Ethics approval The present study was carried out with the endorsement of the Medical Ethics Committee and Experimental Animal Ethics Committee of Huizhou Central People’s Hospital. The use of human tissues conformed the guidelines of the Declaration of Helsinki. Consent to participate Informed consents were obtained from all individual participants, if participants are under 18, from a parent and/or legal guardian. Consent to publish Not applicable. Competing interest The authors declare no competing interests., (© 2024. The Author(s).)