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Published in: Journal of Hematology & Oncology 1/2019

Open Access 01-12-2019 | Research

Genomic landscape and its correlations with tumor mutational burden, PD-L1 expression, and immune cells infiltration in Chinese lung squamous cell carcinoma

Authors: Tao Jiang, Jinpeng Shi, Zhengwei Dong, Likun Hou, Chao Zhao, Xuefei Li, Beibei Mao, Wei Zhu, Xianchao Guo, Henghui Zhang, Ji He, Xiaoxia Chen, Chunxia Su, Shengxiang Ren, Chunyan Wu, Caicun Zhou

Published in: Journal of Hematology & Oncology | Issue 1/2019

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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.
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Metadata
Title
Genomic landscape and its correlations with tumor mutational burden, PD-L1 expression, and immune cells infiltration in Chinese lung squamous cell carcinoma
Authors
Tao Jiang
Jinpeng Shi
Zhengwei Dong
Likun Hou
Chao Zhao
Xuefei Li
Beibei Mao
Wei Zhu
Xianchao Guo
Henghui Zhang
Ji He
Xiaoxia Chen
Chunxia Su
Shengxiang Ren
Chunyan Wu
Caicun Zhou
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2019
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-019-0762-1

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