Comprehensive Pan-Cancer Analysis of the Prognostic Role of KLF Transcription Factor 2 (KLF2) in Human Tumors

Abstract

Background: KLF2 is a transcription factor expressed early in mammalian development that plays a role in many processes of development and disease. Recently, increasing studies revealed that KLF2 plays a key role in the occurrence and progression of cancer. Purpose: The aim of this study was to explore the role of KLF2 in various tumor types using the Cancer Genome Atlas dataset. Methods: Here, we set out to explore the role of KLF2 in 33 tumor types using TCGA (The Cancer Genome Atlas), GEO (Gene Expression Omnibus) dataset, Human Protein Atlas (HPA), UALCAN database, CancerSEA, GSCALite and several bioinformatic tools. Furthermore, we also performed immunohistochemistry and qPCR to further validate the role of KLF2 in multiple cancers and its correlation with prognosis. Results: We found that KLF2 was underexpressed in most tumors and generally predicted poor OS in tumor patients. We found that amplification of KLF2 may be a risk factor for patients with OV (Ovarian serous cystadenocarcinoma). We also analyzed the abundance of checkpoints and markers of specific immune subsets including CD8+ T lymphocytes (T cells), CD4+ T cells, macrophages, and endothelial cells that significantly correlated with the expression level of KLF2 in pan-carcinoma tissues. In some cancers, KLF2 expression levels are positively correlated with gene promoter DNA methylation and drug sensitivity. In addition, we found that KLF2 is involved in single-cell level cell invasion in some cancers. In addition, KLF2 is co-expressed with several intracellular signal transduction genes involved in immune system processes. Immunohistochemistry and qPCR confirmed the low expression of KLF2 in STAD (stomach adenocarcinoma) and renal cancer. Conclusion: Our pan-cancer analysis provides a comprehensive overview of the oncogenic roles of KLF2 in multiple human cancers and can be regarded as a potential prognostic marker and a novel target for cancer immunotherapy.