Aggregate analysis based on TCGA: TTN missense mutation correlates with favorable prognosis in lung squamous cell carcinoma.

Abstract

Lung cancer prevalence with its high mortality rate is a trending topic globally. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. The human gene TTN encoding for TITIN protein is known as major mutation gene in many types of tumor including NSCLC. However, it is still controversial that TTN is a cancer-associated candidate considering tumor heterogeneity and complex genetic structure. In-depth researches on correlation between TTN mutation and NSCLC are still limited and discussable. Related somatic mutation profiles and attached clinical data were from The Cancer Genome Atlas (TCGA) lung project. Clinical relevance analysis of TTN mutation was evaluated using univariate analysis and a binary logistic regressive model. Survival analysis and screening of independent prognostic factors in mutation types were conducted by Cox proportional hazards models and Kaplan-Meier methods. Available data covering lung adenocarcinoma (n = 517) and lung squamous cell carcinoma (n = 492) were analyzed. TTN genetic mutations exhibited significant association with lung squamous cell carcinoma. Patients with lung squamous cell carcinoma possessed favorable overall survival benefits from TTN mutant type and both favorable overall survival and disease-free survival benefits from TTN/TP53 double mutation. For patients with lung squamous cell carcinoma, about 85% of subjects with TTN mutation harbored missense variations, which was an independent indicator of good prognosis. Missense mutation of TTN may act as a beneficial role in lung squamous cell carcinoma, but not in lung adenocarcinoma.