Comprehensive Analysis of KREMEN2 as an Immunotherapeutic and Prognostic Biomarker in Pan-Cancer

Abstract

Background/Aim: Kremen2 has been shown to play an important role in multiple cancers formation as a negative regulatory factor in the Wnt signaling pathway. Our study aimed to explore the potential value of KREMEN2 in pan-cancer and investigate the molecular mechanisms associated with tumor development, providing a basis for prognostic factors and new therapeutic targets for cancer. Materials and Methods: Raw RNA-seq data for 32 types of cancers were obtained from The Cancer Genome Atlas (TCGA), while Xena database provided overall survival (OS) and progression-free survival (PFI) data for TCGA patients. R language was used to identify the association between KREMEN2 and immune response, tumor mutational burden (TMB), and microsatellite instability (MSI). Gene Set Variation Analysis (GSVA) and Gene Set Enrichment Analysis (GSEA) were conducted in pan-cancer. A Nomogram prediction model and weighted gene co-expression network analysis (WGCNA) were constructed in colorectal cancer (CRC). Results: KREMEN2 was found highly expressed in 17 types of tumor tissues compared to normal tissues. KREMEN2 was only correlated with some tumor pathological stages. KREMEN2 with high expression had poor prognosis in pan-cancer. KREMEN2 expression was significantly associated with immune infiltration, immune checkpoints, immune-related genes, commonly regulated tumor-related genes, TMB, and MSI. Moreover, GSVA and GSEA analyses suggested that KREMEN2 played a role in cell cycle in pan-cancer. KREMEN2 expression had a significant impact on the performance of Nomogram prediction model in CRC, and WGCNA analysis indicated that KREMEN2 performed special functions in CRC. Conclusion: The comprehensive pan-cancer analysis revealed that KREMEN2 is a promising tumor prognostic biomarker and a potential anti-tumor immunotherapeutic target in human tumors.