TNF receptor-associated factor 6 in advanced non-small cell lung cancer: clinical and prognostic implications.
OBJECTIVE
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.
Division of Pulmonary and Critical Care, Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-sen University, No 600 Tianhe street, Guangzhou 510630, China. huiliu_sums@yahoo.com.cn
Hui
H
Liu
Tiantuo
T
Zhang
Jin
J
Ye
Hongtao
H
Li
Jing
J
Huang
Xiaodong
X
Li
Benquan
B
Wu
Xubing
X
Huang
Jinghui
J
Hou
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008175:Lung Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism*; D016896:Treatment Outcome
D048029:TNF Receptor-Associated Factor 6