COL22A1 and DNAH8 mutations are associated with tumor mutation burden and prognosis of lung adenocarcinoma patients

Abstract

Abstract Lung cancer is one of the leading causes of death in patients with tumor around the world. Lung adenocarcinoma (LUAD) is most frequent histological subtype in lung cancer. Immune therapy has now become an effective method of treating LUAD. Tumor mutation burden (TMB) shows predictive biomarker potential for identification of cancer patients responding to immune checkpoint inhibitors. The mutation rate of lung adenocarcinoma was the third in various cancers. However, it is not clear whether heterogeneous genetic mutations are associated with TMB and immunity in the patients with LUAD. In our study, First, somatic mutation data of LUAD were downloaded from International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) datasets, and found that 88 same common mutated genes were involved in two cohorts including TNN, TP53, MUC16, CSMD3, RYR2, ZFHX4, LRP1B, USH2A, KRAS, XIRP2, FLG, SPTA1, and so on. Among them, Collagen XXII (COL22A1) and Dynein Axoneme Heavy Chain 8 (DNAH8) mutations were correlated with higher TMB and showed a poorer clinical outcome. Then, In the basis of CIBERSORT algorithm as well as Gene set enrichment analysis (GSEA), we found that COL22A1 or DNAH8 mutation participated in the activation or raising process of immune-related signaling pathways and enhanced antitumor immune reaction. To sum up, COL22A1 or DNAH8 are most common mutated in LUAD, and their mutations are related with higher TMB and poorer prognosis as well as promotes antitumor immunity, which may regard as a biomarker to predict immune reaction.