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

Frontiers in Cell and Developmental Biology

Chengguang Zhao¹  Xueding Cai²  Xiaoying Huang²  Xiaona Xie²  Xiayan Zhu²  Jueqi Sheng²  Yemeng Tang²  Pingping Shu²  Liangxing Wang² 

[1]School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China

[2]The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China

关键词: lung squamous cell carcinoma;    tumor mutation burden;    immunotherapy;    TCGA;    ICGC;   

DOI  :  10.3389/fcell.2021.761758

来源: DOAJ

【 摘 要 】

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 ZFHX4, MUC16, FLG, TP53, LRP1B, TTN, SYNE1, RYR2, CSMD3, USH2A, MUC17, DNAH5, FAM135B, COL11A1, and RYR3. Interestingly, only mutated TTN was related to higher TMB and prognostic outcomes among the 15 mutated genes. Moreover, according to the CIBERSORT algorithm, we revealed that TTN mutation enhanced the antitumor immune response. In conclusion, TTN may have important clinical implications for relevant immune therapy of lung squamous carcinoma.

【 授权许可】

Unknown