Potential Diagnostic Gene Set and Pathway Alterations in Ovarian Cancer

Abstract

Ovarian cancer (OC) is the eighth leading cause of cancer-related deaths among women. This study aimed to evaluate multiple functional genes involved in OC pathogenesis and diagnosis. The expression profiling of Fos Proto-Oncogene, Activator Protein-1 Transcription Factor Subunit (FOS), FOS Like 2, Activator Protein-1 Transcription Factor Subunit (FOSL2), Activator Protein-1 Transcription Factor Subunit Jun Proto-Oncogene (JUN), Matrix Metalloproteinases 2 (MMP-2), Matrix Metalloproteinases 9 (MMP-9) and Tissue Inhibitor of Metalloproteinase 2 (TIMP-2) and Vascular Endothelial Growth Factor (VEGFA) was performed using quantitative real-time PCR (qRT-PCR) in healthy ovary tissues (n=10) and high-grade serous OC tissues (n=10). Functional gene set and pathway analysis were conducted by the g: profiler web server. Gene Expression Profiling Interactive Analysis (GEPIA) was used for pathological stage and overall survival analysis in the Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) datasets. qRT-PCR results revealed that FOS (P-value = 0.0089), MMP-9 (P-value = 0.0029), and VEGFA (P-value = 0.0434) were upregulated.  FOSL2 (P-value = 0.0271), JUN (P-value = 0.0041), and TIMP-2 (P-value = 0.0062) were downregulated. Pathway enrichment analysis showed that the relaxin signaling pathway was the most significant (FDR=9.38e-08) biological pathway. The FOSL2 and TIMP-2 are significant in overall survival and pathological stage analysis, respectively.  The analyzed genes may have the potential for personalized diagnosis and treatment.

Keywords

• ovarian cancer
• gene expression
• diagnosis
• pathway analysis

Ethical Statement

All specimen collection and analysis processes were ethically approved by the Istanbul University Faculty of Medicine Clinical Research Ethics Committee (Permission No: 2019/242) in March 2019.

Over Kanserinde Potansiyel Tanısal Gen Seti ve Yolak Değişiklikleri

Abstract

Over kanseri (OK), kadınlarda kansere bağlı ölümlerin sekizinci en yaygın nedenidir. Bu çalışmada, OK patogenezi ve tanısında rol oynayabilecek çeşitli fonksiyonel genlerin taraması hedeflenmiştir. ‘Fos Proto-Oncogene, Activator Protein-1 Transcription Factor Subunit’ (FOS), ‘FOS Like 2, Activator Protein-1 Transcription Factor Subunit’ (FOSL2), ‘Activator Protein-1 Transcription Factor Subunit Jun Proto-Oncogene’ (JUN), ‘Matrix Metalloproteinases 2’ (MMP-2), ‘Matrix Metalloproteinases 9’ (MMP-9) and ‘Tissue Inhibitor of Metalloproteinase 2’ (TIMP-2) ve ‘Vascular Endothelial Growth Factor’ (VEGFA) genlerinin ekspresyon profilleri, sağlıklı over dokularında (n=10) ve yüksek dereceli seröz OK tümör dokularında (n=10) kantitatif gerçek zamanlı PCR (qRT-PCR) kullanılarak gerçekleştirilmiştir. Fonksiyonel gen seti ve yolak analizi, g: profiler web sunucusu tarafından gerçekleştirilmiştir. ‘Genotype-Tissue Expression’ (GTEx) ve ‘The Cancer Genome Atlas’ (TCGA) veri setlerinde patolojik evre ve genel sağkalım analizi için ‘Gene Expression Profiling Interactive Analysis’ (GEPIA) kullanılmıştır. qRT-PCR sonuçları, FOS (P-değeri = 0,0089), MMP-9 (P-değeri = 0,0029) ve VEGFA (P-değeri = 0,0434) genlerinin ekspresyonunun arttığını göstermektedir.  FOSL2 (P-değeri = 0,0271), JUN (P-değeri = 0,0041) ve TIMP-2 (P-değeri = 0,0062) genlerinin ise ekspresyonu azalmıştır. Yolak zenginleştirme analizi relaksin sinyal yolağının en önemli (FDR=9.38e-08) biyolojik yolak olduğunu göstermiştir. FOSL2 ve TIMP-2, sırasıyla genel sağkalım ve patolojik evre analizinde önemlidir. Analiz edilen genler, kişiselleştirilmiş tanı ve tedavi için potansiyel taşımaktadır.

Keywords

• over kanseri
• gen ekspresyonu
• tanı
• yolak analizi

Ethical Statement

Tüm örnek toplama ve analiz süreçleri İstanbul Üniversitesi Tıp Fakültesi Klinik Araştırmalar Etik Kurulu tarafından Mart 2019'da etik açıdan onaylandı (İzin No: 2019/242).

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