Expression and Functional Analysis of core stemness factors OSKM (OCT4, SOX2, KLF4, and MYC) in Pan-cancer

Abstract

The dedifferentiation process of tumorigenesis and somatic cell reprogramming has some commonness and differences, which is the key question to cancer therapeutic strategy and stem cell applications. To further explore the commonalities and variance between carcinogenesis and induced pluripotent stem cell reprogramming, we investigated the role of stemness factors OSKM (OCT4, SOX2, KLF4, and MYC) in the pan-cancer process using public clinical data. Expression of OSKM in human pan-cancer was analyzed via the Genotype Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) database based on the RNA-seq data of tissues. The correlation of expression between OSKM genes was analyzed via the Tumor Immune Evaluation Resource (TIMER) database, while the STRING tool was used to construct the protein-protein interaction network for OSKM. Prognostic impact of OSKM in pan-cancer was analyzed by Cox proportional hazards regression model. The relationships between OSKM and tumor stemness, tumor microenvironment and immune checkpoint and were performed by Sangerbox platform using Pearson correlation analysis. Our results showed that OSKM were universally expressed and significantly altered in tumors compared with adjacent normal tissues in most tumor types. In addition, correlation analysis revealed the relevance of OSKM genes to patient prognosis, cancer cell stemness, tumor microenvironment or immune checkpoint. However, there is little similarity between these genes in terms of how they function in each cancer type. This study elucidates the different roles of core stemness factors OSKM in pan-cancer, offering potential therapeutic targets for novel anti-cancer strategies and knowledge to minimize the potential carcinogenic effects during stem cell transplantation.