AUTHOR=Xie Xiaona , Tang Yemeng , Sheng Jueqi , Shu Pingping , Zhu Xiayan , Cai Xueding , Zhao Chengguang , Wang Liangxing , Huang Xiaoying 

TITLE=Titin Mutation Is Associated With Tumor Mutation Burden and Promotes Antitumor Immunity in Lung Squamous Cell Carcinoma

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=9

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.761758

DOI=10.3389/fcell.2021.761758

ISSN=2296-634X

ABSTRACT=<p>Lung squamous cell carcinoma (LUSC) is a leading cause of mobidity and mortality worldwide. Recently, there was a shift in the treatment pattern of immune therapy in LUSC patients; merely a small number of patients with non-small cell lung cancer (NSCLC) at advanced stages respond well to immune checkpoint blockade (ICB) therapy, and tumor mutation burden (TMB) is a valuable independent indicator of response to immune therapy. However, specific gene mutations and their relationship with TMB and tumor-infiltrating immunocytes in LUSC are still unclear. In the present paper, our team analyzed the somatically mutated genes from the ICGC (International Cancer Genome Consortium) and TCGA (The Cancer Genome Atlas) datasets and discovered that 15 frequent gene mutations occurred in both cohorts, including <italic>ZFHX4</italic>, <italic>MUC16</italic>, <italic>FLG</italic>, <italic>TP53</italic>, <italic>LRP1B</italic>, <italic>TTN</italic>, <italic>SYNE1</italic>, <italic>RYR2</italic>, <italic>CSMD3</italic>, <italic>USH2A</italic>, <italic>MUC17</italic>, <italic>DNAH5</italic>, <italic>FAM135B</italic>, <italic>COL11A1</italic>, and <italic>RYR3.</italic> Interestingly, only mutated <italic>TTN</italic> was related to higher TMB and prognostic outcomes among the 15 mutated genes. Moreover, according to the CIBERSORT algorithm, we revealed that <italic>TTN</italic> mutation enhanced the antitumor immune response. In conclusion, <italic>TTN</italic> may have important clinical implications for relevant immune therapy of lung squamous carcinoma.</p>