Comparison of Molecular Alterations and Survival Analysis in Uterine Endometrioid Carcinomas and Serous Carcinomas: An In Silico Study

Year 2026, Volume: 7 Issue: 1, 244 - 254, 31.01.2026

Zeynep Sağnak Yılmaz

https://doi.org/10.47482/acmr.1831809

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

Ethical Statement

The study did not require ethical approval

Supporting Institution

None

Thanks

None

Uterin Endometrioid Karsinomlar ve Seröz Karsinomlarda Moleküler Değişiklikler ve Sağkalım Analizlerinin Karşılaştırılması: İn Silico Çalışma

Abstract

Giriş: Endometrioid ve seröz endometriyal karsinomlar, belirgin moleküler, epigenetik ve klinik özellikler gösteren iki farklı alt tiptir. Bu çalışma, bu iki alt tip arasındaki mutasyonları, sağkalımı ve biyolojik yolak analizlerini in silico yaklaşımla karşılaştırmayı amaçlamıştır.
Yöntem: Kanser Genom Atlas Uterin Korpus Endometrial Karsinom (Pan-Kanser Atlas) veri setinden endometrioid (n=399) ve seröz (n=109) karsinomlar cBioPortal aracılığıyla analiz edilmiştir. Genomik mutasyonlar, mRNA ekspresyon düzeyleri, MSİ (mikrosatellit instabilite) sensör skorları ve genel sağkalım karşılaştırılmıştır. Farklı eksprese edilen genler (DEG’ler) belirlenmiştir. p<0.05 ve q<0.05 istatistiksel olarak anlamlı kabul edilmiştir. Yolak zenginleştirme analizleri g:Profiler ve WebGestalt kullanılarak gerçekleştirilmiştir.
Bulgular: 662 genomik mutasyon ve 10757 mRNA anlamlı farklılık göstermiştir. Endometrioid karsinomlarda PTEN, ARID1A, CTNNB1, CTCF, KMT2B, KRAS, NEB ve RNF43 en anlamlı DEG’ler olarak bulunurken; seröz karsinomlarda TP53 ve PPP2R1A en baskın mutasyonlardır (p<0.001 ve q<0.001). MSİ-High oranı endometrioid tümörlerde daha yüksektir (31.6% vs. 0.9%, p = 7.215e-3). Median sağkalım endometrioid tümörlerde 102.83 ay, seröz tümörlerde ise 63.91 ay olarak saptanmıştır (p=5.28e-8). Yolak analizleri proteazom, hatalı eşleşme onarımı, DNA replikasyonu, spliceozom ve baz eksizyon onarım yolaklarının yanı sıra gelişimsel ve metabolik yolaklarda da zenginleşme olduğunu göstermiştir.
Sonuç: Endometrioid tümörlerin PI3K–PTEN–AKT–mTOR ve WNT/β-katenin eksenlerinde kademeli genetik bozulmalar yoluyla geliştiği; buna karşılık seröz tümörlerin TP53 mutasyonları, yüksek genomik instabilite ve DNA onarım yolak kusurları ile ilişkili olduğu tespit edilmiştir. Bu moleküler farklılık, seröz karsinomların daha agresif klinik davranışını ve daha düşük sağkalım oranlarını açıklamakta olup, alt tipe özgü tanısal ve terapötik stratejilerin önemini vurgulamaktadır.

Keywords

farklı ifade edilen genler , endometrial karsinom , biyoinformatik , yolak zenginleştirma analizi

Ethical Statement

Çalışmanın etik onaya ihtiyacı yoktu

Supporting Institution

Yok

Thanks

Yok

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