The role of the CDCA gene family in tumor stemness maintenance and drug sensitivity

Background The cell division cycle-associated ( CDCA ) gene family regulates cell cycle progression and is frequently dysregulated in multiple cancers. However, its roles in tumor stemness maintenance and drug sensitivity remain unclear. This study aimed to investigate the expression of the CDCAs in cancers and their associations with tumor stemness and drug sensitivity, with a particular focus on the effects of CDCA2 on stemness and drug sensitivity in lung and colorectal cancers. Methods CDCA s expression and prognostic value were analyzed using The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) datasets, while correlations with stemness [DNA methylation-based stemness scores (DNAss) and RNA-based stemness scores (RNAss)] and drug sensitivity [Genomics of Drug Sensitivity in Cancer (GDSC)] were assessed. Functional validation was performed by knocking down CDCA2 in lung and colorectal cancer cell lines. Results Pan-cancer analysis revealed that CDCA s were broadly upregulated across tumor types and were significantly associated with poor prognosis in multiple cancers (P<0.05). Most CDCA s showed positive associations with tumor stemness based on RNAss and DNAss analyses (r>0.3, P<0.05). Drug sensitivity analysis indicated that CDCA expression was closely related to responses to various anticancer agents. Experimental validation demonstrated that CDCA2 knockdown significantly inhibited proliferation of lung and colorectal cancer cells, reduced stemness marker expression, and increased sensitivity to oxaliplatin. Conclusions CDCAs are widely upregulated in cancers and associated with poor prognosis, enhanced tumor stemness, and drug resistance. CDCA2 promotes proliferation and chemoresistance, highlighting its potential as a prognostic biomarker and therapeutic target.