TNF receptor-associated factor 6 in advanced non-small cell lung cancer: clinical and prognostic implications.

PURPOSE: Tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) represents a central point of convergence for the signal transduction by the TNFR and the IL-lR/TLR superfamilies. We conducted this retrospective clinical study focusing on TRAF6 expression associated with overall survival and chemotherapeutical sensitivity in a large population with advanced non-small cell lung cancer (NSCLC). METHODS: A total of 324 patients with stage III and IV NSCLC were retrospectively enrolled. Immunohistochemistry was performed to evaluate the expression of TRAF6, apoptosis-related proteins Bcl-2, Bax, Fas, and FasL, as well as the density of CD8(+) and FOXP3(+) tumor infiltrating lymphocytes (TILs) in tumor microenvironment. RESULTS: A total of 193 carcinomas (59.6 %) were identified as high expression of TRAF6. TRAF6 expression was not significantly related with histology and clinic stage. No obvious correlation of TRAF6 expression with apoptosis-related protein and TILs density was identified. TRAF6 status was correlated inversely with response to chemotherapy in overall patients (response rates 24.9 and 32.8 %, for patients with high-TRAF6 and low-TRAF6 tumors, respectively, P = 0.039). However, multivariate logistic regression analysis could not identify TRAF6 status as an independent predictor for the response to chemotherapy in overall cohort (95 % CI: 0.91-3.32, P = 0.065). The overall survival was not significantly associated with TRAF6 expression (P = 0.616). CONCLUSIONS: Our results provide new insight for the biological properties and clinical relevance of the TRAF6 in NSCLC. TRAF6 is a promise target for therapeutic strategies against cancer.