Abstract
This study investigates the expression patterns and clinical relevance of KLHL35 (Kelch-Like Family Member 35) across various cancer types, with a focus on colorectal cancer. Comprehensive analysis of RNA sequencing data from The Cancer Genome Atlas (TCGA) and protein expression data from the Human Protein Atlas (HPA) revealed significant overexpression of KLHL35 in 13 tumor types, including colorectal cancer. Increased KLHL35 expression was associated with poor clinical outcomes, including overall survival (OS), progression-free interval (PFI), and disease-specific survival (DSS). Receiver operating characteristic (ROC) curve analysis suggested promising but exploratory diagnostic value for KLHL35, with area under the curve (AUC) values exceeding 0.9 in colorectal cancer. Functional enrichment analyses suggested potential associations between KLHL35 and cell cycle/apoptosis pathways, while immune infiltration correlations hinted at a possible role in immune microenvironment remodeling. In vitro assays confirmed KLHL35’s role in promoting cancer cell proliferation, invasion, and migration. These findings suggest that KLHL35 could serve as a valuable diagnostic and prognostic biomarker and a potential therapeutic target, particularly in colorectal cancer. While these findings nominate KLHL35 as a candidate for therapeutic targeting, further mechanistic studies are required to validate its function.” SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12672-025-03715-5.