AUTHOR=Shi Xuezhong , Dong Ani , Jia Xiaocan , Zheng Guowei , Wang Nana , Wang Yuping , Yang Chaojun , Lu Jie , Yang Yongli 

TITLE=Integrated analysis of single-cell and bulk RNA-sequencing identifies a signature based on T-cell marker genes to predict prognosis and therapeutic response in lung squamous cell carcinoma

JOURNAL=Frontiers in Immunology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.992990

DOI=10.3389/fimmu.2022.992990

ISSN=1664-3224

ABSTRACT=Cancer immunotherapy is an increasingly successful strategy for treating patients with advanced or conventionally drug-resistant cancers. T cells have been proved to play important roles in anti-tumor and tumor microenvironment shaping, while these roles have not been explained in lung squamous cell carcinoma (LUSC). Therefore, we aimed to explore the expression profiles of T-cell marker genes and construct a prognostic signature in LUSC. Single-cell RNA-sequencing (scRNA-seq) data was downloaded from the gene expression omnibus (GEO) database to screen T-cell marker genes by cell subpopulation annotation. Bulk RNA-sequencing data and clinical information were downloaded from the cancer genome atlas (TCGA) database to develop a prognosis signature. We investigated the association of different risk groups with survival analysis, gene set enrichment analysis (GSEA), tumor mutational burden (TMB), tumor immune microenvironment (TIME) and drug sensitivity. Based on 72 T-cell marker genes identified by scRNA-seq analysis, we constructed a prognostic signature containing 5 genes in the training cohort, which was further validated in the testing cohort and GEO cohort. The areas under the receiver operating characteristic curve at 1, 3, and 5 years were 0.614, 0.713 and 0.702 in the training cohort, 0.669, 0.603 and 0.645 in the testing cohort, 0.661, 0.628 and 0.590 in the GEO cohort, respectively. Furthermore, we created a highly reliable nomogram to facilitate clinical application. GSEA analysis showed that immune-related pathways were mainly enriched in the high-risk group. TIME indicated that high-risk group exhibited higher immune score, stromal score, and immune cell infiltration levels. Moreover, genes of the immune checkpoints and human leukocyte antigen family were overexpressed in high-risk group. Higher TMB was associated with better prognosis. Additionally, drug sensitivity revealed that low-risk group was sensitive to 8 chemotherapeutic drugs and high-risk group to 4 chemotherapeutic drugs. Our study reveals a novel prognostic signature based on T-cell marker genes, which provides a new target and theoretical support for T-cell therapy for LUSC patients.