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

Abstract

Transmembrane tumor necrosis factor-α (tmTNF-α) is known to induce the activation of NF-κB to protect tumor cells. Upregulation of tmTNF-α leads to resistance to apoptosis and induces drug resistance in breast cancer. However, the expression of tmTNF-α in colorectal cancer (CRC) and its association with clinical outcome in CRC have remained unclear. In this study, we examined the tmTNF-α expression in CRC by immunohistochemistry and western blotting, assessed the prognostic value of tmTNF-α 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-α 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-α expression in the CRC tissues comparing with the adjacent tissues. The tmTNF-α 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-α 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-α influenced the chemotherapeutic effect of 5-Fluorouracil on colon cancer cells. Altogether, these data indicated the stageII/III CRC patients with high tmTNF-α expression were more likely to have a worse prognosis than patients with low tmTNF-α expression and tmTNF-α may influence the chemotherapeutic effect of 5-Fluorouracil. The mechanism for these observations warrants further study.

• Authors: Xiaogai Li, Shihai Wang, HuiJun Ren, Junfen Ma, Xiaoxu Sun, Nan Li, Cailin Liu, Kaida Huang, Min Xu, Liang Ming
• Journal: Cancer biology & therapy (Cancer Biol Ther) Vol. 17 Issue 6 Pg. 684-92 (06 02 2016) ISSN: 1555-8576 [Electronic] United States
• PMID: 27224726 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Tumor Necrosis Factor-alpha
• Fluorouracil

Topics

• Chemotherapy, Adjuvant
• Colorectal Neoplasms (drug therapy, mortality, pathology)
• Female
• Fluorouracil (pharmacology)
• Humans
• Male
• Prognosis
• Signal Transduction
• Survival Analysis
• Tumor Necrosis Factor-alpha (pharmacology)