Comparison of Molecular Alterations and Survival Analysis in Uterine Endometrioid Carcinomas and Serous Carcinomas: An In Silico Study
Abstract
Background: Endometrioid and serous endometrial carcinomas exhibit distinct molecular, epigenetic, and clinical characteristics. This study aimed to compare mutations, survival, and biological pathway analysis between these two subtypes using an in silico approach.
Methods: Endometrioid (n=399) and serous (n=109) carcinomas from The Cancer Genome Atlas Uterine Corpus Endometrial Carcinoma (PanCancer Atlas) dataset were analyzed via cBioPortal. Genomic mutations, mRNA expression levels, MSI (microsatellite instability) sensor scores and overall survival were compared. Differentially mutated genes were identified. P< 0.0.5 and q< 0.05 were considered statistically significant. Pathway enrichment analyses were performed using g:Profiler and WebGestalt.
Results: 662 genomic mutations and 10757 mRNA expression levels showed significant differences. In endometrioid carcinomas, PTEN, ARID1A, CTNNB1, CTCF, KMT2B, KRAS, NEB, and RNF43 were the most significantly mutated genes; whereas in serous carcinomas, TP53 and PPP2R1A were the predominantly mutated genes (p<0.001 and q<0.001). The MSI-High rate was higher in endometrioid tumors (31.6% vs. 0.9%, p = 7.215e-3). The median survival was 102.83 months in endometrioid tumors and 63.91 months in serous tumors (p=5.28e-8). Pathway analyses revealed enrichments in proteasome, mismatch repair, DNA replication, spliceosome, base excision repair, as well as developmental and metabolic pathways.
Conclusion: It was observed that endometrioid tumors develop through gradual genetic disruptions within the PI3K– PTEN–AKT–mTOR and WNT/β-catenin axes, whereas serous tumors develop through high genomic instability driven by TP53 mutations, and DNA repair pathway defects. This molecular distinction explains the more aggressive clinical behavior and lower survival rates of serous carcinomas, emphasizing the importance of specific diagnostic and therapeutic strategies.
Keywords
Endometrial carcinoma, bioinformatics, differentially expressed genes, pathway enrichment analysis
Supporting Institution
None
Ethical Statement
The study did not require ethical approval
Thanks
None
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