Abstract

Objectives Radiosensitivity Index (RSI) can predict intrinsic radiotherapy sensitivity. We analyzed multiomics characteristics in lung squamous cell carcinoma between high and low RSI groups, which may help understand the underlying molecular mechanism of radiosensitivity and guide optional treatment for patients in the future. Methods The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) data were used to download clinical data, mRNA, microRNA, and lncRNA expression. Differential analyses, including mRNA, miRNA, lncRNA, and G.O. and KEGG, and GSVA analyses, were performed with R. Gene set enrichment analysis was done by GSEA. miRNA-differentially expressed gene network and ceRNA network were analyzed and graphed by the Cytoscape software. Results In TCGA data, 542 patients were obtained, including 171 in the low RSI group (LRSI) and 371 in the high RSI group (HRSI). In RNAseq, 558 significantly differentially expressed genes (DEGs) were obtained. KRT6A was the most significantly upregulated gene and IDO1 was the most significantly downregulated gene. In miRNAseq, miR-1269a was the most significantly upregulated. In lncRNAseq, LINC01871 was the most upregulated. A 66-pair interaction between differentially expressed genes and miRNAs and an 11-pair interaction between differential lncRNAs and miRNAs consisted of a ceRNA network, of which miR-184 and miR-490-3p were located in the center. In the GEO data, there were 40 DEGs. A total of 17 genes were founded in both databases, such as ADAM23, AHNAK2, BST2, COL11A1, CXCL13, FBN2, IFI27, IFI44L, MAGEA6, and PTGR1. GSVA analysis revealed 31 significant pathways. GSEA found 87 gene sets enriched in HRSI and 91 gene sets in LRSI. G.O. and KEGG of RNA expression levels revealed that these genes were most enriched in T cell activation and cytokine−cytokine receptor interaction. Conclusions Patients with lung squamous cell carcinoma have different multiomics characteristics between two groups. These differences may have an essential significance with radiotherapy effect.

Highlights

  • Lung cancer, the first killer globally, was estimated at 131,880 deaths in 2021 [1]

  • In The Cancer Genome Atlas (TCGA) data, based on Radiosensitivity Index (RSI) scores (0.50 tangents), 542 Lung squamous cell carcinoma (LUSC) patients were divided into RSI high grouping (HRSI) and low grouping (LRSI), of which 171 were in low RSI group (LRSI) and 371 were in high RSI group (HRSI)

  • The results showed that there was an obvious survival difference between HRSI and LRSI (p = 0:029)

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Summary

Introduction

The first killer globally, was estimated at 131,880 deaths in 2021 [1]. Lung squamous cell carcinoma (LUSC) accounts for 20–30% of NSCLCs [2].Radiotherapy is one of the effective cancer treatments. The first killer globally, was estimated at 131,880 deaths in 2021 [1]. Lung squamous cell carcinoma (LUSC) accounts for 20–30% of NSCLCs [2]. Radiotherapy is one of the effective cancer treatments. Radiosensitivity Index (RSI) is a novel model of tumor radiosensitivity. Based on the expression of 10 genes (JUN, STAT1, SUMO1, IRF1, HDAC9, ABL1, CDK1, RELA, PRRT2, and AR), RSI could predict intrinsic radiotherapy sensitivity and treatment response [3]. This model is widely used in cancer, such as breast cancer and NSCLCs [4,5,6]

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