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- Title
Genomic landscape and its correlations with tumor mutational burden, PD-L1 expression, and immune cells infiltration in Chinese lung squamous cell carcinoma.
- Authors
Jiang, Tao; Shi, Jinpeng; Dong, Zhengwei; Hou, Likun; Zhao, Chao; Li, Xuefei; Mao, Beibei; Zhu, Wei; Guo, Xianchao; Zhang, Henghui; He, Ji; Chen, Xiaoxia; Su, Chunxia; Ren, Shengxiang; Wu, Chunyan; Zhou, Caicun
- Abstract
Introduction: To depict the genomic landscape of Chinese early-stage lung squamous cell carcinoma (LUSC) and investigate its correlation with tumor mutation burden (TMB), PD-L1 expression, and immune infiltrates. Methods: Whole-exome sequencing was performed on 189 surgically resected LUSC. TMB was defined as the sum of nonsynonymous single nucleotide and indel variants. CD8+ tumor-infiltrating lymphocyte (TIL) density and PD-L1 expression were evaluated by immunohistochemistry. Six immune infiltrates were estimated using an online database. Results: The median TMB was 9.43 mutations per megabase. Positive PD-L1 expression and CD8+ TILs density were identified in 24.3% and 78.8%. PIK3CA amplification was associated with significantly higher TMB (P = 0.036). Frequent genetic alterations had no impact on PD-L1 expression but PIK3CA amplification and KEAP1 mutation were independently associated with significantly lower CD8+ TIL density (P < 0.001, P = 0.005, respectively). Low TMB and high CD8+ TIL density were independently associated with longer disease-free survival (DFS) while none of them could individually predict the overall survival (OS). Combination of TMB and PD-L1 expression or TMB and CD8+ TIL density could stratify total populations into two groups with distinct prognosis. Classifying tumor-immune microenvironment based on PD-L1 expression and CD8+ TIL density showed discrepant genomic alterations but similar TMB, clinical features, and OS. Notably, patients with different smoking status had distinct prognostic factors. Conclusion: The combination of TMB, PD-L1 expression, immune infiltrates, and smoking status showed the feasibility to subgroup stratification in Chinese patients with early-stage LUSC, which might be helpful for future design of personalized immunotherapy trials in LUSC.
- Publication
Journal of Hematology & Oncology, 2019, Vol 12, Issue 1, pN.PAG
- ISSN
1756-8722
- Publication type
Article
- DOI
10.1186/s13045-019-0762-1