Abstract

BackgroundTumor stem cells play important roles in the survival, proliferation, metastasis and recurrence of tumors. We aimed to identify new prognostic biomarkers for lung squamous cell carcinoma (LUSC) based on the cancer stem cell theory.MethodsRNA-seq data and relevant clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. Weighted gene coexpression network analysis (WGCNA) was applied to identify significant modules and hub genes, and prognostic signatures were constructed with the prognostic hub genes.ResultsLUSC patients in the TCGA database have higher mRNA expression-based stemness index (mRNAsi) in tumor tissue than in adjacent normal tissue. In addition, some clinical features and outcomes were highly correlated with the mRNAsi. WGCNA revealed that the pink and yellow modules were the most significant modules related to the mRNAsi; the top 10 hub genes in the pink module were enriched mostly in epidermal development, the secretory granule membrane, receptor regulator activity and the cytokine-cytokine receptor interaction. The protein–protein interaction (PPI) network revealed that the top 10 hub genes were significantly correlated with each other at the transcriptional level. In addition, the top 10 hub genes were all highly expressed in LUSC, and some were differentially expressed in different TNM stages. Regarding the survival analysis, the nomogram of a prognostic signature with three hub genes showed high predictive value.ConclusionmRNAsi-related hub genes could be a potential biomarker of LUSC.

Highlights

  • Lung cancer ranks first in morbidity (11.6%) and mortality (18.4%) according to the latest worldwide survey of 20 regions from five continents and is the leading male cancer in both developed and developing countries (Bray et al, 2018) among all cancers

  • There was a significant difference between the mRNA expression-based stemness index (mRNAsi) in normal tissues and lung squamous cell carcinoma (LUSC) tissues; we aimed to identify Differentially Expressed Genes (DEGs) based on the comparison between the two

  • We identified the significance of the mRNAsi in the clinical characteristics of patients with LUSC with the help of data from the The Cancer Genome Atlas (TCGA) database and the mRNAsi corresponding to each sample

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Summary

Introduction

Lung cancer ranks first in morbidity (11.6%) and mortality (18.4%) according to the latest worldwide survey of 20 regions from five continents and is the leading male cancer in both developed and developing countries (Bray et al, 2018) among all cancers. A recent study used bioinformatics methods found that FOXM1 and MYBL2, which are involved in the process of cell proliferation, can be used as potential biomarkers and therapeutic targets of NSCLC (Ahmed, 2019). This theory provides a new direction and idea for us to understand the origin and nature of the tumor and clinical treatment. We aimed to identify new prognostic biomarkers for lung squamous cell carcinoma (LUSC) based on the cancer stem cell theory

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