Journals / Hacettepe Journal of Biology and Chemistry / 2026 / Volume: 54 Issue: 3

Potential Diagnostic Gene Set and Pathway Alterations in Ovarian Cancer

Over Kanserinde Potansiyel Tanısal Gen Seti ve Yolak Değişiklikleri

Ece Gümüşoğlu-Acar(ISTANBUL UNIVERSITY, FACULTY OF SCIENCE)0000-0003-3807-0330
Berkcan Dogan(BURSA ULUDAG UNIVERSITY, SCHOOL OF MEDICINE)0000-0001-8061-8131
Samet Topuz(ISTANBUL UNIVERSITY, İSTANBUL FACULTY OF MEDICINE)0000-0002-9069-0185
Tuba Gunel(İstanbul Üniversitesi)0000-0003-3514-5210
Pages
—
Publication Date
2026-06-30
🏛️Bibliographic metadata and full text access for this article are provided via DergiPark.
DergiPark Record ↗
✨

AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

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.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:Ovarian cancer (OC) is the eighth leading cause of cancer-related deaths among women.
📊
Key Findings & Data: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).
💡
Conclusion & Impact: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.
🔬Design:Research Article
📍Scope:Comprehensive Sample
⚙️Variables:ovarian cancer · gene expression · diagnosis

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.

Özet

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.

🔖

Cite This Article

Gümüşoğlu-Acar, E., Dogan, B., Bilir, M. U., Kirmizitas, T. S., Topuz, S., Gunel, T. (2026). Potential Diagnostic Gene Set and Pathway Alterations in Ovarian Cancer. Hacettepe Journal of Biology and Chemistry, Volume: 54 Issue: 3. https://doi.org/10.15671/hjbc.1796263

📄 Full Text PDF Viewer

📄

PDF görüntüleyici hazırlanıyor...

References (48)

  1. L.A. Torre, B. Trabert, C.E. DeSantis, K.D. Miller, G. Samimi, C.D. Runowicz, M.M. Gaudet, A. Jemal, R.L. Siegel, Ovarian cancer statistics, CA Cancer J. Clin., 68(4) (2018) 284-296.
  2. M.J. Zheng, X. Li, Y.X. Hu, H. Dong, R. Gou, X. Nie, Q. Liu, H. Ying-Ying, J.J. Liu, B. Lin, Identification of molecular marker associated with ovarian cancer prognosis using bioinformatics analysis and experiments, J. Cell Physiol., 234(7) (2019) 11023-11036.
  3. R. Singh, A. Som, Common miRNAs, candidate genes and their interaction network across four subtypes of epithelial ovarian cancer, Bioinformation., 17(8) (2021) 748-759.
  4. A. Ghose, A. Bolina, I. Mahajan, S.A. Raza, M. Clarke, A. Pal, E. Sanchez, K.S. Rallis, S. Boussios, Hereditary ovarian cancer: towards a cost-effective prevention strategy, Int. J. Environ. Res. Public Health., 19(19) (2022).
  5. D. Yang, Y. He, B. Wu, Y. Deng, N. Wang, M. Li, Y. Liu, Integrated bioinformatics analysis for the screening of hub genes and therapeutic drugs in ovarian cancer, J. Ovarian Res., 13(1) (2020) 10.
  6. A.A. Alshamrani, Roles of microRNAs in ovarian cancer tumorigenesis: two decades later, what have we learned?, Front. Oncol., 10 (2020) 1084.
  7. A. Ghose, S.V.N. Gullapalli, N. Chohan, A. Bolina, M. Moschetta, E. Rassy, S. Boussios, Applications of proteomics in ovarian cancer: dawn of a new era, Proteomes., 10(2) (2022).
  8. Q. Liu, X. Yang, Y. Yin, H. Zhang, F. Yin, P. Guo, X. Zhang, C. Sun, S. Li, Y. Han, Z. Yang, Identifying the role of oxidative stress-related genes as prognostic biomarkers and predicting the response of immunotherapy and chemotherapy in ovarian cancer, Oxid. Med. Cell. Longev., 2022(1) (2022) 6575534.
  9. A. Ghose, L. McCann, S. Makker, U. Mukherjee, S.V.N. Gullapalli, J. Erekkath, S. Shih, I. Mahajan, E. Sanchez, M. Uccello, M. Moschetta, S. Adeleke, S. Boussios, Diagnostic biomarkers in ovarian cancer: advances beyond CA125 and HE4, Ther. Adv. Med. Oncol., 16 (2024) 1-12.
  10. T. Gunel, B. Dogan, E. Gumusoglu, M.K. Hosseini, S. Topuz, K. Aydinli, Regulation of HMGA2 and KRAS genes in epithelial ovarian cancer by miRNA hsa-let-7d-3p, J. Cancer Res. Ther., 15(6) (2019) 1321-1327.
  11. E. Gumusoglu-Acar, T. Gunel, Ovarian cancer biomarkers, in: S.A. Farghaly (Ed.), Advances in Diagnosis and Management of Ovarian Cancer, Springer International Publishing, Cham, 2022, pp. 27-42.
  12. E. Gumusoglu-Acar, T. Gunel, M.K. Hosseini, B. Dogan, E.E. Tekarslan, B. Gurdamar, N. Cevik, U. Sezerman, S. Topuz, K. Aydinli, Metabolic pathways of potential miRNA biomarkers derived from liquid biopsy in epithelial ovarian cancer, Oncol. Lett., 25(4) (2023) 142.
  13. S. Mahner, C. Baasch, J. Schwarz, S. Hein, L. Wölber, F. Jänicke, K. Milde-Langosch, C-Fos expression is a molecular predictor of progression and survival in epithelial ovarian carcinoma, Br. J. Cancer., 99(8) (2008) 1269-1275.
  14. R.M. Escalona, M. Bilandzic, P. Western, E. Kadife, G. Kannourakis, J.K. Findlay, N. Ahmed, TIMP-2 regulates proliferation, invasion and STAT3-mediated cancer stem cell-dependent chemoresistance in ovarian cancer cells, BMC Cancer., 20(1) (2020) 960.
  15. X. Li, Z. Hu, H. Shi, C. Wang, J. Lei, Y. Cheng, Inhibition of VEGFA increases the sensitivity of ovarian cancer cells to chemotherapy by suppressing VEGFA-mediated autophagy, Onco Targets Ther., 13 (2020) 8161-8171.
  16. Q. Hao, J. Li, Q. Zhang, F. Xu, B. Xie, H. Lu, X. Wu, X. Zhou, Single-cell transcriptomes reveal heterogeneity of high-grade serous ovarian carcinoma, Clin. Transl. Med., 11(8) (2021) e500.
  17. A. Kicman, M. Niczyporuk, M. Kulesza, J. Motyka, S. Ławicki, Utility of matrix metalloproteinases in the diagnosis, monitoring and prognosis of ovarian cancer patients, Cancer Manag. Res., 14 (2022) 3359-3382.
  18. J. Li, L. Zhou, H. Jiang, L. Lin, Y. Li, Inhibition of FOSL2 aggravates the apoptosis of ovarian cancer cells by promoting the formation of inflammasomes, Genes Genomics., 44(1) (2022) 29-38.
  19. P.J. Olbromski, P. Pawlik, A. Bogacz, S. Sajdak, Identification of new molecular biomarkers in ovarian cancer using the gene expression profile, J. Clin. Med., 11(13) (2022).
  20. K. Ono, T. Tanaka, T. Tsunoda, O. Kitahara, C. Kihara, A. Okamoto, K. Ochiai, T. Takagi, Y. Nakamura, Identification by cDNA microarray of genes involved in ovarian carcinogenesis, Cancer Res., 60(18) (2000) 5007-5011.
  21. B. Dogan, E. Gumusoglu, E. Ulgen, O.U. Sezerman, T. Gunel, Integrated bioinformatics analysis of validated and circulating miRNAs in ovarian cancer, Genomics Inform., 20(2) (2022) e20.
  22. A. Pawar, O.R. Chowdhury, R. Chauhan, S. Talole, A. Bhattacharjee, Identification of key gene signatures for the overall survival of ovarian cancer, J. Ovarian Res., 15(1) (2022) 12.
  23. D. Szklarczyk, A.L. Gable, K.C. Nastou, D. Lyon, R. Kirsch, S. Pyysalo, N.T. Doncheva, M. Legeay, T. Fang, P. Bork, L.J. Jensen, C. von Mering, The STRING database in 2021: customizable protein–protein networks, and functional characterization of user-uploaded gene/measurement sets, Nucleic Acids Res., 49(D1) (2020) D605-D612.
  24. U. Raudvere, L. Kolberg, I. Kuzmin, T. Arak, P. Adler, H. Peterson, J. Vilo, g:Profiler: a web server for functional enrichment analysis and conversions of gene lists (2019 update), Nucleic Acids Res., 47(W1) (2019) W191-W198.
  25. M. Cox, A.E.R. Kartikasari, P.R. Gorry, K.L. Flanagan, M. Plebanski, Potential impact of human cytomegalovirus infection on immunity to ovarian tumours and cancer progression, Biomedicines., 9(4) (2021) 351.
  26. I. Saani, N. Raj, R. Sood, S. Ansari, H.A. Mandviwala, E. Sanchez, S. Boussios, Clinical challenges in the management of malignant ovarian germ cell tumours, Int. J. Environ. Res. Public Health., 20(12) (2023) 6089.
  27. S. Akter, M.A. Rahman, M.N. Hasan, H. Akhter, P. Noor, R. Islam, Y. Shin, M.D.H. Rahman, M.S. Gazi, M.N. Huda, N.M. Nam, J. Chung, S. Han, B. Kim, I. Kang, J. Ha, W. Choe, T.G. Choi, S.S. Kim, Recent advances in ovarian cancer: therapeutic strategies, potential biomarkers, and technological improvements, Cells., 11(4) (2022) 650.
  28. S. Kongara, S. Prakasha, B. Anbaalagan, S. Pathak, J. Miya, S. Taqui, H. Khalil Almoallim, S. Alharbi, S. Raghavan, Performance evaluation of optimized convolutional neural network mechanism in the detection and classification of ovarian cancer, Multimed. Tools Appl., 83 (2024) 1-24.
  29. C. López-Portugués, M. Montes-Bayón, P. Díez, Biomarkers in ovarian cancer: towards personalized medicine, Proteomes., 12(1) (2024) 8.
  30. S. Shah, A. Cheung, M. Kutka, M. Sheriff, S. Boussios, Epithelial ovarian cancer: providing evidence of predisposition genes, Int. J. Environ. Res. Public Health., 19(13) (2022) 8113.
  31. R. Retamales-Ortega, L. Oróstica, C. Vera, P. Cuevas, A. Hernández, I. Hurtado, M. Vega, C. Romero, Role of nerve growth factor (NGF) and miRNAs in epithelial ovarian cancer, Int. J. Mol. Sci., 18(3) (2017) 507.
  32. F. Aliyuda, M. Moschetta, A. Ghose, K. Sofia Rallis, M. Sheriff, E. Sanchez, E. Rassy, S. Boussios, Advances in ovarian cancer treatment beyond PARP inhibitors, Curr. Cancer Drug Targets., 23(6) (2023) 433-446.
  33. J. Deng, X. Bai, X. Feng, J. Ni, J. Beretov, P. Graham, Y. Li, Inhibition of PI3K/Akt/mTOR signaling pathway alleviates ovarian cancer chemoresistance through reversing epithelial-mesenchymal transition and decreasing cancer stem cell marker expression, BMC Cancer., 19(1) (2019) 618.
  34. F. Bejjani, E. Evanno, K. Zibara, M. Piechaczyk, I. Jariel-Encontre, The AP-1 transcriptional complex: local switch or remote command?, Biochim. Biophys. Acta Rev. Cancer., 1872(1) (2019) 11-23.
  35. R.D. Motrich, G.M. Castro, B.L. Caputto, Old players with a newly defined function: Fra-1 and c-Fos support growth of human malignant breast tumors by activating membrane biogenesis at the cytoplasm, PLoS One., 8(1) (2013) e53211.
  36. Y. Hao, L. Zhu, L. Yan, J. Liu, D. Liu, N. Gao, M. Tan, S. Gao, B. Lin, c-Fos mediates α1,2-fucosyltransferase 1 and Lewis y expression in response to TGF-β1 in ovarian cancer, Oncol. Rep., 38(6) (2017) 3355-3366.
  37. E.J. Ruiz, L. Lan, M.E. Diefenbacher, E.M. Riising, C. Da Costa, A. Chakraborty, J.D. Hoeck, B. Spencer-Dene, G. Kelly, J.P. David, E. Nye, J. Downward, A. Behrens, JunD, not c-Jun, is the AP-1 transcription factor required for Ras-induced lung cancer, JCI Insight., 6(13) (2021) e124985.
  38. L. Zeng, J. Qian, F. Zhu, F. Wu, H. Zhao, H. Zhu, The prognostic values of matrix metalloproteinases in ovarian cancer, J. Int. Med. Res., 48(1) (2020) 1-9.
  39. Y. Zhang, Q. Chen, Relationship between matrix metalloproteinases and the occurrence and development of ovarian cancer, Braz. J. Med. Biol. Res., 50 (2017) e6104.
  40. S.L. Poon, C. Klausen, G.L. Hammond, P.C. Leung, 37-kDa laminin receptor precursor mediates GnRH-II-induced MMP-2 expression and invasiveness in ovarian cancer cells, Mol. Endocrinol., 25(2) (2011) 327-338.
  41. P. Saharinen, L. Eklund, K. Pulkki, P. Bono, K. Alitalo, VEGF and angiopoietin signaling in tumor angiogenesis and metastasis, Trends Mol. Med., 17(7) (2011) 347-362.
  42. K. Jang, M. Kim, C.A. Gilbert, F. Simpkins, T.A. Ince, J.M. Slingerland, VEGFA activates an epigenetic pathway upregulating ovarian cancer-initiating cells, EMBO Mol. Med., 9(3) (2017) 304-318.
  43. W. Wang, F. Ren, Q. Wu, D. Jiang, H. Li, H. Shi, MicroRNA-497 suppresses angiogenesis by targeting vascular endothelial growth factor A through the PI3K/AKT and MAPK/ERK pathways in ovarian cancer, Oncol. Rep., 32(5) (2014) 2127-2133.
  44. M. Sopo, M. Anttila, K. Hämäläinen, A. Kivelä, S. Ylä-Herttuala, V.-M. Kosma, L. Keski-Nisula, H. Sallinen, Expression profiles of VEGF-A, VEGF-D and VEGFR1 are higher in distant metastases than in matched primary high grade epithelial ovarian cancer, BMC Cancer., 19(1) (2019) 584.
  45. S. Lawicki, G.E. Będkowska, E. Gacuta-Szumarska, M. Szmitkowski, The plasma concentration of VEGF, HE4 and CA125 as a new biomarkers panel in different stages and sub-types of epithelial ovarian tumors, J. Ovarian Res., 6(1) (2013) 45.
  46. H.E. Burston, O.A. Kent, L. Communal, M.L. Udaskin, R.X. Sun, K.R. Brown, E. Jung, K.E. Francis, J. La Rose, J. Lowitz, R. Drapkin, A.M. Mes-Masson, R. Rottapel, Inhibition of relaxin autocrine signaling confers therapeutic vulnerability in ovarian cancer, J. Clin. Invest., 131(7) (2021) e142677.
  47. J. Feng, H. Zhang, F. Li, Investigating the relevance of major signaling pathways in cancer survival using a biologically meaningful deep learning model, BMC Bioinformatics., 22(1) (2021) 47.
  48. Á. Nagy, G. Munkácsy, B. Győrffy, Pancancer survival analysis of cancer hallmark genes, Sci. Rep., 11(1) (2021) 6047.