Identification of Immune Subtypes of Lung Squamous Cell Carcinoma by Integrative Genome-Scale Analysis.

Liyuan Yin,Qiang Wu,Yan Li,Qinghua Zhou,Jia Hu,Wen Zhang,Dan Pu,Xiaoqian Zhai,Yiyun Lin,Tangel Chang

doi:10.3389/fonc.2021.778549

Abstract

BackgroundCharacterization of the tumor microenvironment is helpful to understand the tumor immune environment of lung cancer and help predict the prognosis.MethodsFirst, immune subtypes were identified by consensus subtype among lung squamous carcinoma (LUSC) patients. Immune cell infiltration was evaluated by CIBERSORT and ESTIMATE analyses. Then, based on differentially expressed genes (DEGs) identified, a risk score model was constructed. Finally, gene FPR1 was validated by using YTMLC-90.FindingsLUSC samples were divided into four heterogeneous immune subtypes, with significantly different prognoses with subtype 4 having the poorest overall survival (OS). The immune infiltration score showed that subtype 4 was characterized as immune enriched and fibrotic, while subtype 3 was tumor enriched. DEG analysis showed that upregulated genes in subtype 4 were enriched of neutrophil and exhausted T cell-related biological processes. Based on a univariate Cox regression model, prognostic 7 immune-related genes were combined to construct a risk score model and able to predict OS rates in the validation datasets. Wound healing and transwell assay were conducted to evaluate the invasion property after activating the gene FPR1. InterpretationThe analysis of tumor immune microenvironments among LUSC subtypes may provide new insights into the strategy of immunotherapy.

Highlights

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide [1]
We tested the prognosis of four subtypes by using the Cancer Genome Atlas (TCGA)-lung squamous cell carcinoma (LUSC) RNA-Seq data
We analyzed immune infiltration differences in the TCGA LUSC cohort and identified four subtypes based on their immune-related gene expression profile

Summary

Introduction

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide [1]. Non-small cell lung cancer is divided into lung adenocarcinoma, lung squamous cell carcinoma (LUSC), and large cell carcinoma [2]. Immune checkpoint inhibitors (ICIs) have been approved as the first-line treatment for advanced-stage lung squamous cell carcinoma with PD-L1 expression >1% [7,8,9]. The heterogeneity of the tumor microenvironment brings confusing treatment response among individual patients [10]. The development of more effective treatments is hindered by incomplete knowledge of the genetic determinant of immune responsiveness. Methods: First, immune subtypes were identified by consensus subtype among lung squamous carcinoma (LUSC) patients.

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