Comprehensive Analysis of The Expression and Prognosis For KRTs in LUSC Based on Bioinformatics Analysis

Abstract

Keratins (KRTs), a family of genes that encode a series of intermediate flament proteins, which expressed in epithelial cells of various tissues and had been identified as being involved in various tumors. Previous evidences indicated that KRTs were implicated in tumorigenesis and development of lung cancer. However, a comprehensive analysis of KRTs in lung squamous cell carcinoma (LUSC) and their roles in the tumorigenesis and progression of this disease is lacking. Therefore, we investigated the transcriptional level, proteomic level, and prognosis of KRTs in patients with LUSC from TCGA, Gene Expression Profifiling Interactive Analysis (GEPIA), Human Protein Atlas (HPA), Kaplan-Meier Plotter, and cBioPortal databases. We confirmed that the expression levels of KRT5, KRT6A, KRT6B, KRT6C, KRT13, KRT14, KRT15, KRT16, KRT17, KRT19, and KRT23 were higher in LUSC tissues than in adjacent normal lung tissues. Survival analyses using Kaplan-Meier Plotter database and TCGA database revealed that the high expression levels of KRT5, KRT6A, KRT6B, KRT6C, KRT13, KRT14, KRT15, KRT16, KRT17, KRT19, and KRT23 were associated with poor prognosis in patients with LUSC. ROC curves indicated that KRTs had poor roles in predicting the overall survival (OS) of LUSC patients. KRTs and their 50 most frequently altered neighbor genes were mainly enriched in epidermis development, keratinization, keratinocyte differentiation, Rap1 signaling pathway, and transcriptional misregulation in cancer. The results of clinical data analyses indicated that the expression levels of KRT13, KRT16, KRT17, and KRT19 were positively correlated with nodal metastasis, the expression level of KRT15 and KRT17 were positively correlated with primary tumor, and the high expression level of KRT15 was positively correlated with TNM stage. Our study may provide new theoretical basis and research direction for the discovery of potential therapeutic targets and new prognostic biomarkers in patients with LUSC.

Meta-Analysis of Esophageal Cancer Transcriptomes Using Independent Component Analysis

“…Thus, our study revealed other potential tumor-associated biomarker genes, namely keratin genes (KRTs), involved in EMT. The genes of the keratin family are responsible for the expression of various intermediate filament proteins found in epithelial tissues of various organs and they are differentially expressed in numerous human tumor malignancies as they are involved in tumor related processes such as invasion, metastasis, proliferation, and apoptosis of tumor cells ( Zheng et al, 2021 ). Several studies showed the association of KRT13 with multiple cancer types including prostate, head and neck cancer, urothelial cancer ( Li et al, 2016 ).…”