Identification of Non-Invasive Biomarkers for Early Detection of Ovarian Cancer
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Early Detection, Non-Invasive, Ovarian Cancer
Abstract
Ovarian cancer is one of the most lethal gynecologic malignancies due to late diagnosis. Early detection is critical for improving survival rates, yet current screening methods are inadequate. To identify and validate non-invasive biomarkers for the early detection of ovarian cancer, focusing on improving diagnostic accuracy and patient outcomes. This study utilized proteomic and genomic approaches, including mass spectrometry for protein profiling and next-generation sequencing for analyzing cfDNA and miRNAs. Blood samples from patients with early-stage ovarian cancer, healthy controls, and individuals with benign conditions were analyzed. The combination of CA-125 and HE4 biomarkers significantly increased sensitivity (85%) and specificity (90%) for early detection of ovarian cancer compared to CA-125 alone. Proteomic analysis identified significant differences in protein profiles between cancer patients and healthy controls. Genomic analysis revealed specific mutations in cfDNA associated with ovarian cancer. The study demonstrates that a combination of CA-125 and HE4, along with multi-omic approaches, can enhance the early detection of ovarian cancer, providing a basis for the development of more accurate diagnostic tests. Further clinical trials are necessary to validate these findings.
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References
Adani, G., Filippini, T., Wise, L. A., Halldorsson, T. I., Blaha, L., & Vinceti, M. (2020). Dietary Intake of Acrylamide and Risk of Breast, Endometrial, and Ovarian Cancers: A Systematic Review and Dose–Response Meta-analysis. Cancer Epidemiology, Biomarkers & Prevention, 29(6), 1095–1106. https://doi.org/10.1158/1055-9965.EPI-19-1628
Asante, D.-B., Calapre, L., Ziman, M., Meniawy, T. M., & Gray, E. S. (2020). Liquid biopsy in ovarian cancer using circulating tumor DNA and cells: Ready for prime time? Cancer Letters, 468, 59–71. https://doi.org/10.1016/j.canlet.2019.10.014
Boussios, S., Rassy, E., Moschetta, M., Ghose, A., Adeleke, S., Sanchez, E., Sheriff, M., Chargari, C., & Pavlidis, N. (2022). BRCA Mutations in Ovarian and Prostate Cancer: Bench to Bedside. Cancers, 14(16), 3888. https://doi.org/10.3390/cancers14163888
Carver, T., Hartley, S., Lee, A., Cunningham, A. P., Archer, S., Babb De Villiers, C., Roberts, J., Ruston, R., Walter, F. M., Tischkowitz, M., Easton, D. F., & Antoniou, A. C. (2021). CanRisk Tool—A Web Interface for the Prediction of Breast and Ovarian Cancer Risk and the Likelihood of Carrying Genetic Pathogenic Variants. Cancer Epidemiology, Biomarkers & Prevention, 30(3), 469–473. https://doi.org/10.1158/1055-9965.EPI-20-1319
Charkhchi, P., Cybulski, C., Gronwald, J., Wong, F. O., Narod, S. A., & Akbari, M. R. (2020). CA125 and Ovarian Cancer: A Comprehensive Review. Cancers, 12(12), 3730. https://doi.org/10.3390/cancers12123730
Cheng, S., Xu, C., Jin, Y., Li, Y., Zhong, C., Ma, J., Yang, J., Zhang, N., Li, Y., Wang, C., Yang, Z., & Wang, Y. (2020). Artificial Mini Dendritic Cells Boost T Cell–Based Immunotherapy for Ovarian Cancer. Advanced Science, 7(7), 1903301. https://doi.org/10.1002/advs.201903301
Gao, T., Zhang, X., Zhao, J., Zhou, F., Wang, Y., Zhao, Z., Xing, J., Chen, B., Li, J., & Liu, S. (2020). SIK2 promotes reprogramming of glucose metabolism through PI3K/AKT/HIF-1? pathway and Drp1-mediated mitochondrial fission in ovarian cancer. Cancer Letters, 469, 89–101. https://doi.org/10.1016/j.canlet.2019.10.029
Hao, L., Wang, J.-M., Liu, B.-Q., Yan, J., Li, C., Jiang, J.-Y., Zhao, F.-Y., Qiao, H.-Y., & Wang, H.-Q. (2021). m6A-YTHDF1-mediated TRIM29 upregulation facilitates the stem cell-like phenotype of cisplatin-resistant ovarian cancer cells. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1868(1), 118878. https://doi.org/10.1016/j.bbamcr.2020.118878
Hong, T., Lei, G., Chen, X., Li, H., Zhang, X., Wu, N., Zhao, Y., Zhang, Y., & Wang, J. (2021). PARP inhibition promotes ferroptosis via repressing SLC7A11 and synergizes with ferroptosis inducers in BRCA-proficient ovarian cancer. Redox Biology, 42, 101928. https://doi.org/10.1016/j.redox.2021.101928
Hu, Z., Cai, M., Zhang, Y., Tao, L., & Guo, R. (2020). miR-29c-3p inhibits autophagy and cisplatin resistance in ovarian cancer by regulating FOXP1/ATG14 pathway. Cell Cycle, 19(2), 193–206. https://doi.org/10.1080/15384101.2019.1704537
Huang, H., Wang, Y., Kandpal, M., Zhao, G., Cardenas, H., Ji, Y., Chaparala, A., Tanner, E. J., Chen, J., Davuluri, R. V., & Matei, D. (2020). FTO-Dependent N6 -Methyladenosine Modifications Inhibit Ovarian Cancer Stem Cell Self-Renewal by Blocking cAMP Signaling. Cancer Research, 80(16), 3200–3214. https://doi.org/10.1158/0008-5472.CAN-19-4044
Huang, J., Chan, W. C., Ngai, C. H., Lok, V., Zhang, L., Lucero-Prisno, D. E., Xu, W., Zheng, Z.-J., Elcarte, E., Withers, M., Wong, M. C. S., & on behalf of NCD Global Health Research Group of Association of Pacific Rim Universities (APRU). (2022). Worldwide Burden, Risk Factors, and Temporal Trends of Ovarian Cancer: A Global Study. Cancers, 14(9), 2230. https://doi.org/10.3390/cancers14092230
Jiang, Y., Wang, C., & Zhou, S. (2020). Targeting tumor microenvironment in ovarian cancer: Premise and promise. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, 1873(2), 188361. https://doi.org/10.1016/j.bbcan.2020.188361
Kobayashi, M., Sawada, K., Miyamoto, M., Shimizu, A., Yamamoto, M., Kinose, Y., Nakamura, K., Kawano, M., Kodama, M., Hashimoto, K., & Kimura, T. (2020). Exploring the potential of engineered exosomes as delivery systems for tumor-suppressor microRNA replacement therapy in ovarian cancer. Biochemical and Biophysical Research Communications, 527(1), 153–161. https://doi.org/10.1016/j.bbrc.2020.04.076
Kuroki, L., & Guntupalli, S. R. (2020). Treatment of epithelial ovarian cancer. BMJ, m3773. https://doi.org/10.1136/bmj.m3773
Lau, T. S., Chan, L. K. Y., Man, G. C. W., Wong, C. H., Lee, J. H. S., Yim, S. F., Cheung, T. H., McNeish, I. A., & Kwong, J. (2020). Paclitaxel Induces Immunogenic Cell Death in Ovarian Cancer via TLR4/IKK2/SNARE-Dependent Exocytosis. Cancer Immunology Research, 8(8), 1099–1111. https://doi.org/10.1158/2326-6066.CIR-19-0616
Le Saux, O., Ray-Coquard, I., & Labidi-Galy, S. I. (2021). Challenges for immunotherapy for the treatment of platinum resistant ovarian cancer. Seminars in Cancer Biology, 77, 127–143. https://doi.org/10.1016/j.semcancer.2020.08.017
Lecker, L. S. M., Berlato, C., Maniati, E., Delaine-Smith, R., Pearce, O. M. T., Heath, O., Nichols, S. J., Trevisan, C., Novak, M., McDermott, J., Brenton, J. D., Cutillas, P. R., Rajeeve, V., Hennino, A., Drapkin, R., Loessner, D., & Balkwill, F. R. (2021). TGFBI Production by Macrophages Contributes to an Immunosuppressive Microenvironment in Ovarian Cancer. Cancer Research, 81(22), 5706–5719. https://doi.org/10.1158/0008-5472.CAN-21-0536
Li, X., Pan, Y., Chen, H., Duan, Y., Zhou, S., Wu, W., Wang, S., & Liu, B. (2020). Specific Near-Infrared Probe for Ultrafast Imaging of Lysosomal ?-Galactosidase in Ovarian Cancer Cells. Analytical Chemistry, 92(8), 5772–5779. https://doi.org/10.1021/acs.analchem.9b05121
Liu, W., Wang, W., Wang, X., Xu, C., Zhang, N., & Di, W. (2020). Cisplatin-stimulated macrophages promote ovarian cancer migration via the CCL20-CCR6 axis. Cancer Letters, 472, 59–69. https://doi.org/10.1016/j.canlet.2019.12.024
Marchetti, C., De Felice, F., Romito, A., Iacobelli, V., Sassu, C. M., Corrado, G., Ricci, C., Scambia, G., & Fagotti, A. (2021). Chemotherapy resistance in epithelial ovarian cancer: Mechanisms and emerging treatments. Seminars in Cancer Biology, 77, 144–166. https://doi.org/10.1016/j.semcancer.2021.08.011
McMullen, M., Karakasis, K., Madariaga, A., & Oza, A. M. (2020). Overcoming Platinum and PARP-Inhibitor Resistance in Ovarian Cancer. Cancers, 12(6), 1607. https://doi.org/10.3390/cancers12061607
Miyamoto, T., Murakami, R., Hamanishi, J., Tanigaki, K., Hosoe, Y., Mise, N., Takamatsu, S., Mise, Y., Ukita, M., Taki, M., Yamanoi, K., Horikawa, N., Abiko, K., Yamaguchi, K., Baba, T., Matsumura, N., & Mandai, M. (2022). B7-H3 Suppresses Antitumor Immunity via the CCL2–CCR2–M2 Macrophage Axis and Contributes to Ovarian Cancer Progression. Cancer Immunology Research, 10(1), 56–69. https://doi.org/10.1158/2326-6066.CIR-21-0407
Mukherjee, A., Chiang, C.-Y., Daifotis, H. A., Nieman, K. M., Fahrmann, J. F., Lastra, R. R., Romero, I. L., Fiehn, O., & Lengyel, E. (2020). Adipocyte-Induced FABP4 Expression in Ovarian Cancer Cells Promotes Metastasis and Mediates Carboplatin Resistance. Cancer Research, 80(8), 1748–1761. https://doi.org/10.1158/0008-5472.CAN-19-1999
Nacarelli, T., Fukumoto, T., Zundell, J. A., Fatkhutdinov, N., Jean, S., Cadungog, M. G., Borowsky, M. E., & Zhang, R. (2020). NAMPT Inhibition Suppresses Cancer Stem-like Cells Associated with Therapy-Induced Senescence in Ovarian Cancer. Cancer Research, 80(4), 890–900. https://doi.org/10.1158/0008-5472.CAN-19-2830
Nash, Z., & Menon, U. (2020). Ovarian cancer screening: Current status and future directions. Best Practice & Research Clinical Obstetrics & Gynaecology, 65, 32–45. https://doi.org/10.1016/j.bpobgyn.2020.02.010
Rickard, B. P., Conrad, C., Sorrin, A. J., Ruhi, M. K., Reader, J. C., Huang, S. A., Franco, W., Scarcelli, G., Polacheck, W. J., Roque, D. M., Del Carmen, M. G., Huang, H.-C., Demirci, U., & Rizvi, I. (2021). Malignant Ascites in Ovarian Cancer: Cellular, Acellular, and Biophysical Determinants of Molecular Characteristics and Therapy Response. Cancers, 13(17), 4318. https://doi.org/10.3390/cancers13174318
Samadi Pakchin, P., Fathi, M., Ghanbari, H., Saber, R., & Omidi, Y. (2020). A novel electrochemical immunosensor for ultrasensitive detection of CA125 in ovarian cancer. Biosensors and Bioelectronics, 153, 112029. https://doi.org/10.1016/j.bios.2020.112029
Sun, H., Wang, H., Wang, X., Aoki, Y., Wang, X., Yang, Y., Cheng, X., Wang, Z., & Wang, X. (2020). Aurora-A/SOX8/FOXK1 signaling axis promotes chemoresistance via suppression of cell senescence and induction of glucose metabolism in ovarian cancer organoids and cells. Theranostics, 10(15), 6928–6945. https://doi.org/10.7150/thno.43811
Tossetta, G., Fantone, S., Montanari, E., Marzioni, D., & Goteri, G. (2022). Role of NRF2 in Ovarian Cancer. Antioxidants, 11(4), 663. https://doi.org/10.3390/antiox11040663
Wan, C., Keany, M. P., Dong, H., Al-Alem, L. F., Pandya, U. M., Lazo, S., Boehnke, K., Lynch, K. N., Xu, R., Zarrella, D. T., Gu, S., Cejas, P., Lim, K., Long, H. W., Elias, K. M., Horowitz, N. S., Feltmate, C. M., Muto, M. G., Worley, M. J., … Hill, S. J. (2021). Enhanced Efficacy of Simultaneous PD-1 and PD-L1 Immune Checkpoint Blockade in High-Grade Serous Ovarian Cancer. Cancer Research, 81(1), 158–173. https://doi.org/10.1158/0008-5472.CAN-20-1674
Wang, J., Ding, W., Xu, Y., Tao, E., Mo, M., Xu, W., Cai, X., Chen, X., Yuan, J., & Wu, X. (2020). Long non-coding RNA RHPN1-AS1 promotes tumorigenesis and metastasis of ovarian cancer by acting as a ceRNA against miR-596 and upregulating LETM1. Aging, 12(5), 4558–4572. https://doi.org/10.18632/aging.102911
Wang, Y., Zhao, G., Condello, S., Huang, H., Cardenas, H., Tanner, E. J., Wei, J., Ji, Y., Li, J., Tan, Y., Davuluri, R. V., Peter, M. E., Cheng, J.-X., & Matei, D. (2021). Frizzled-7 Identifies Platinum-Tolerant Ovarian Cancer Cells Susceptible to Ferroptosis. Cancer Research, 81(2), 384–399. https://doi.org/10.1158/0008-5472.CAN-20-1488
Xiong, J., Wu, M., Chen, J., Liu, Y., Chen, Y., Fan, G., Liu, Y., Cheng, J., Wang, Z., Wang, S., Liu, Y., & Zhang, W. (2021). Cancer-Erythrocyte Hybrid Membrane-Camouflaged Magnetic Nanoparticles with Enhanced Photothermal-Immunotherapy for Ovarian Cancer. ACS Nano, 15(12), 19756–19770. https://doi.org/10.1021/acsnano.1c07180
Xuan, Y., Wang, H., Yung, M. M., Chen, F., Chan, W.-S., Chan, Y.-S., Tsui, S. K., Ngan, H. Y., Chan, K. K., & Chan, D. W. (2022). SCD1/FADS2 fatty acid desaturases equipoise lipid metabolic activity and redox-driven ferroptosis in ascites-derived ovarian cancer cells. Theranostics, 12(7), 3534–3552. https://doi.org/10.7150/thno.70194
Yang, Z., Xu, H., & Zhao, X. (2020). Designer Self?Assembling Peptide Hydrogels to Engineer 3D Cell Microenvironments for Cell Constructs Formation and Precise Oncology Remodeling in Ovarian Cancer. Advanced Science, 7(9), 1903718. https://doi.org/10.1002/advs.201903718
Zhang, K., Erkan, E. P., Jamalzadeh, S., Dai, J., Andersson, N., Kaipio, K., Lamminen, T., Mansuri, N., Huhtinen, K., Carpén, O., Hietanen, S., Oikkonen, J., Hynninen, J., Virtanen, A., Häkkinen, A., Hautaniemi, S., & Vähärautio, A. (2022). Longitudinal single-cell RNA-seq analysis reveals stress-promoted chemoresistance in metastatic ovarian cancer. Science Advances, 8(8), eabm1831. https://doi.org/10.1126/sciadv.abm1831
Zhang, M., Cheng, S., Jin, Y., Zhao, Y., & Wang, Y. (2021). Roles of CA125 in diagnosis, prediction, and oncogenesis of ovarian cancer. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, 1875(2), 188503. https://doi.org/10.1016/j.bbcan.2021.188503
Zhang, Q.-F., Li, J., Jiang, K., Wang, R., Ge, J., Yang, H., Liu, S.-J., Jia, L.-T., Wang, L., & Chen, B.-L. (2020). CDK4/6 inhibition promotes immune infiltration in ovarian cancer and synergizes with PD-1 blockade in a B cell-dependent manner. Theranostics, 10(23), 10619–10633. https://doi.org/10.7150/thno.44871
Zheng, F., Zhang, Y., Chen, S., Weng, X., Rao, Y., & Fang, H. (2020). Mechanism and current progress of Poly ADP-ribose polymerase (PARP) inhibitors in the treatment of ovarian cancer. Biomedicine & Pharmacotherapy, 123, 109661. https://doi.org/10.1016/j.biopha.2019.109661
Zhou, J., Jiang, Y., Chen, H., Wu, Y., & Zhang, L. (2020). RETRACTED: Tanshinone I attenuates the malignant biological properties of ovarian cancer by inducing apoptosis and autophagy via the inactivation of PI3K/AKT/mTOR pathway. Cell Proliferation, 53(2), e12739. https://doi.org/10.1111/cpr.12739
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Copyright (c) 2025 Haruto Takahashi, Kaito Tanaka, Luis Santos
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