Molecular correlates and prognostic value of tmTNF- expression in colorectal cancer of 5-Fluorouracil-Based Adjuvant Therapy

摘要

Transmembrane tumor necrosis factor- (tmTNF-) is known to induce the activation of NF-B to protect tumor cells. Upregulation of tmTNF- leads to resistance to apoptosis and induces drug resistance in breast cancer. However, the expression of tmTNF- in colorectal cancer (CRC) and its association with clinical outcome in CRC have remained unclear. In this study, we examined the tmTNF- expression in CRC by immunohistochemistry and western blotting, assessed the prognostic value of tmTNF- related to the recurrence/metastasis and survival of stage II/III CRC by the Kaplan-Meier survival curve and Cox regression model, and also explored the role of tmTNF- expression on the chemotherapeutic efficacy of 5-Fluorouracil by flow cytometry assay and cell counting kit-8 (CCK-8) in vitro. Overall, we found that 77 (78.6%) out of 98 patients exhibited higher tmTNF- expression in the CRC tissues comparing with the adjacent tissues. The tmTNF- expression was correlated with Differentiation (P = 0.019), TNM stage (P = 0.039), Lymph nodes metastasis (P = 0.024) and Lymphovascular invasion (P = 0.027) but not related with Age (P = 0.617), Gender (P = 0.625), Tumor location (P = 0.138), Perforation/Obstruction (P = 1.000), Depth of invasion (P = 0.327), and microsatellite instability status (P = 0.150). The prognostic analyses showed that high tmTNF- expression patients was significantly associated with decreased Disease-Free Survival (P = 0.0209) and Overall Survival (P = 0.0163). CCK-8 results suggested that the tmTNF- influenced the chemotherapeutic effect of 5-Fluorouracil on colon cancer cells. Altogether, these data indicated the stageII/III CRC patients with high tmTNF- expression were more likely to have a worse prognosis than patients with low tmTNF- expression and tmTNF- may influence the chemotherapeutic effect of 5-Fluorouracil. The mechanism for these observations warrants further study.