Brca1 Mutasyonlu Over Kanserinde Hotaır–Mir-34a–CCND1 Ekseninin Fonksiyonel ve Klinik Önemi

Abstract

Giriş:BRCA1 mutasyonlu over kanseri, DNA çift sarmal kırıklarının onarımında bozulma ve homolog rekombinasyon yetersizliği ile karakterizedir; bu durum tümör biyolojisini ve terapötik yanıtları belirgin biçimde etkiler. Rekabetçi endojen RNA ağları, kanser progresyonunda önemli düzenleyici mekanizmalar olarak ortaya çıkmıştır. Bu çalışma, BRCA1 mutasyonlu over kanserinde HOTAIR–miR34a–CCND1 ekseninin fonksiyonel ve klinik önemini araştırmayı amaçlamıştır. Yöntemler: Yüksek dereceli seröz over kanseri hastalarına ait transkriptomik ve klinik veriler, GDC portalı üzerinden TCGA-OV kohortundan elde edilmiştir. Diferansiyel gen ekspresyon analizi edgeR ile gerçekleştirilmiş; yolak zenginleştirme analizi clusterProfiler ve KEGG kullanılarak yapılmıştır. Sağkalım analizleri Kaplan–Meier eğrileriyle değerlendirilmiştir. Bulgular: HOTAIR–miR34a–CCND1 ekseni, BRCA1 mutasyonlu over kanseri dokularında, vahşi tip olgulara kıyasla farklı ekspresyon profilleri göstermiştir. Kaplan–Meier sağkalım analizi, bu genlerin ekspresyon düzeylerine göre genel sağkalımda istatistiksel olarak anlamlı bir fark olmadığını ortaya koymuştur (p > 0.05). Bununla birlikte, KEGG yolak zenginleştirme analizi, bu genlerin kanserle ilişkili mikroRNA yolaklarında yer aldığını göstermiştir; bu durum, doğrudan sağkalım ilişkisinin olmamasına rağmen tümör progresyonunda potansiyel rollerine işaret etmektedir. Sonuç: HOTAIR–miR-34a–CCND1 ekseni, BRCA1 mutasyonlu over kanserinde potansiyel bir prognostik biyobelirteç ve terapötik hedef olabilir. Bu da HOTAIR inhibisyonu, miR-34a replasmanı veya PARP ve CDK4/6 inhibitörleriyle kombinasyon gibi yeni tedavi stratejilerinin geliştirilmesini desteklemektedir.

Keywords

• brca1 mutant
• over kanseri
• hotair
• microrna
• ccnd1

Functional And Clinical Significance Of The Hotaır–Mir-34a–CCND1 Axis İn Brca1-Mutated Ovarian Cancer

Abstract

Objectives: BRCA1-mutated ovarian cancer is characterized by impaired DNA double-strand break repair and homologous recombination deficiency, leading to distinct tumor biology and therapeutic responses. Competing endogenous RNA networks have emerged as important regulatory mechanisms in cancer progression. This study aimed to investigate the functional and clinical significance of the HOTAIR–miR34a–CCND1 axis in BRCA1-mutated ovarian cancer. Methods: Transcriptomic and clinical data of high-grade serous ovarian cancer patients were obtained from the TCGA-OV cohort via the GDC portal. Differential gene expression analysis was performed using edgeR, while pathway enrichment analysis was conducted with clusterProfiler and KEGG. Survival analyses were evaluated using Kaplan–Meier curves. Results: The HOTAIR–miR34a–CCND1 axis displayed distinct expression profiles in BRCA1-mutated ovarian cancer tissues compared to wild-type cases. Kaplan–Meier survival analysis revealed no statistically significant differences in overall survival based on the expression levels of these genes (p > 0.05). However, KEGG pathway enrichment analysis demonstrated that these genes are involved in cancer-associated microRNA pathways, suggesting their potential role in tumor progression despite the lack of direct survival association. Conclusion: The HOTAIR–miR-34a–CCND1 axis may represent a potential prognostic biomarker and therapeutic target in BRCA1-mutated ovarian cancer, supporting the development of novel strategies such as HOTAIR inhibition, miR-34a replacement, or combination with PARP and CDK4/6 inhibitors.

Keywords

• brca1 mutation
• ovarian neoplasms
• hotair
• micrornas
• ccnd1

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