Multi-omics analysis and functional validation of CHEK1 as an independent prognostic biomarker in Pancreatic cancer

Abstract

Background Pancreatic cancer is a highly aggressive tumor with a poor prognosis due to challenging early diagnosis and limited treatment options. CHEK1, a crucial cell cycle regulator, is important in tumor development, but its role in pancreatic cancer remains under-researched in terms of expression, function, and regulation. Objective To study the effect of CHEK1 on proliferation, migration and cell cycle of pancreatic cancer, and to construct a prognostic prediction model to investigate the effect of CHEK1 on the prognosis of pancreatic cancer. Methods We conducted a systematic investigation into the expression characteristics and biological functions of CHEK1 in pancreatic cancer, utilizing an integration of bioinformatics analyses and in vitro experiments. Initially, we performed an in-depth analysis of CHEK1 expression profiles and their clinical significance in pancreatic cancer, drawing on data from several public databases, including UALCAN, TNMplot, and TISIDB. Subsequently, we validated the impact of CHEK1 on the malignant biological behaviors of pancreatic cancer cells, specifically focusing on proliferation and migration, through a series of in vitro cellular experiments. Results The findings revealed that CHEK1 expression levels were significantly upregulated in pancreatic cancer tissues, which correlated positively with tumor pathological grade. KEGG pathway enrichment analysis further indicated that CHEK1 exerts critical regulatory functions across multiple oncogenic pathways, including cellular proliferation, G2/M checkpoint control, DNA replication, and DNA damage repair. In vitro experimental demonstrated that CHEK1 overexpression substantially increased both the proliferative progression and migratory capacity of pancreatic cancer cells. Conclusions Our study indicates that high CHEK1 expression could be an independent prognostic marker for pancreatic cancer and may drive cancer progression by influencing DNA replication and G2/M checkpoint pathways. These insights offer a foundation for future research and targeted precision therapy involving CHEK1.