Differentiated regulation of immune-response related genes between LUAD and LUSC subtypes of lung cancers.

Mengzhu Chen,Xiu-Jie Wang,Jie Du,Xiuying Liu,Lixin Xia

doi:10.18632/oncotarget.13346

Abstract

Lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) are the two major subtypes of lung cancer, with LUSC exhibits faster progression rate than LUAD. To investigate the roles of immune-response related genes (IRGs) in lung cancer progression, we used LUAD and LUSC samples at different cancer progression stages, and identified that the expression profiles of IRGs could serve as a better classification marker for cancerous tissues of both LUAD and LUSC. We found that the expression changes of IRGs were different between LUAD and LUSC. Cell cycle promoting genes, including KIFs and proteasomes, showed faster up-regulation in LUSC, whereas immune response promoting genes, including MHC molecules and chemokines, were more rapidly repressed in LUSC. Comparative pathway analysis revealed that members of the Toll-like receptor and T cell receptor signaling pathways exhibited diverged expression changes between LUAD and LUSC, especially at the early cancer stages. Our results revealed the difference of LUAD and LUSC from the immune response point of view, and provided new clues for the differential treatment of LUAD and LUSC.

Highlights

Lung cancer is a common and severe disease which ranks the top among cancers worldwide in terms of mortality for both men and women [1, 2]
We considered patients with available RNA-seq data from both the tumor and matched normal samples as valid subjects, data from a total of 36 lung adenocarcinoma (LUAD) patients and 32 Lung squamous cell carcinoma (LUSC) patients at different cancer stages were included in this study (Supplementary Table S1 and Supplementary Table S2)
Using a cutoff threshold of fold change > 2 and FDR < 0.1, differentially expressed immune-response related genes (DEIRGs) at each stage of LUAD or LUSC as compared to the corresponding normal tissues were identified by the edgeR software and used in the following analysis (Table 1)

Summary

Introduction

Lung cancer is a common and severe disease which ranks the top among cancers worldwide in terms of mortality for both men and women [1, 2]. Most of diagnosed lung cancers are malignant epithelial tumors, which could be further classified into small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC). NSCLC counts for about 85-90% of lung cancers, among which the most common subtypes are lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) [3]. According to the tumor node metastasis (TNM) taxonomy, both LUAD and LUSC can be classified into four stages, namely stages I, II, III and IV [4]. Stages II and III usually indicate the intermediate, regional lymphatic metastatic stages, of which stage III has a higher lymphatic metastasis degree than stage II. Each stage can be further divided into A and B sub-stages, of which sub-stage B has higher cancer degree than sub-stage A

Methods

Results

Conclusion