Expression of DR5 and c‑FLIP proteins as novel prognostic biomarkers for non‑small cell lung cancer patients treated with surgical resection and chemotherapy

TRAILR2 (DR5), one of the death receptors, can activate the extrinsic apoptosis pathway, while cellular FLICEinhibitory protein (cFLIP) can inhibit this pathway. Both of them play important roles in the occurrence and development of most tumors. To date, there is no relevant report concerning the relationship between expression of DR5 and cFLIP protein and clinicopathological/prognostic implications in patients with nonsmall cell lung cancer (NSCLC) treated with surgical resection and chemotherapy. Thus, the aim of the present study was to investigate the potential prognostic significance of DR5 and cFLIP in NSCLC patients and their predictive roles in the chemotherapeutic response. In the present study, DR5 and cFLIP were detected by immunohistochemistry (IHC) in tissue microarrays of NSCLC. The results showed that the expression levels of DR5 and cFLIP were significantly higher in lung squamous cell carcinoma (SCC) and lung adenocarcinoma (ADC) tissues compared with levels noted in the noncancerous control lung tissues (all P<0.05). In addition, DR5 expression was significantly increased in lung ADC (P<0.001), whereas, cFLIP was higher in lung SCC (P<0.001) and smoker patients with clinical stage III (P=0.019, P=0.016, respectively). In addition, NSCLC patients with overexpression of DR5 and loss of cFLIP expression exhibited a higher overall survival (OS) rate as determined by KaplanMeier analysis (P=0.029, P=0.038, respectively). Multivariate analysis confirmed that high expression of DR5 and loss of cFLIP expression were independent favorable prognostic factors for NSCLC patients (P=0.016, P=0.035, respectively). In conclusion, overexpression of DR5 and loss of cFLIP expression may serve as novel favorable prognostic biomarkers for NSCLC patients treated with chemotherapy after radical resection and used as predictors for tumor response to chemotherapy drugs.