{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T17:49:52Z","timestamp":1791568192226,"version":"4.3.4"},"reference-count":32,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["OMICS: A Journal of Integrative Biology"],"abstract":"<jats:p>\n                    High-grade serous ovarian cancer (HGSOC) is the most lethal gynecological malignancy, with a poor 5-year survival rate. Many patients also experience relapse of the disease due to chemotherapy resistance, highlighting an urgent need for new therapeutic modalities. Among the genomic alterations implicated in HGSOC progression, amplification of cyclin E1 (\n                    <jats:italic toggle=\"yes\">CCNE1<\/jats:italic>\n                    ) has emerged as a frequent and clinically significant event, occurring in \u223c19% of cases. In this hypothesis-generating study, we explore the prognostic relevance of\n                    <jats:italic toggle=\"yes\">CCNE1<\/jats:italic>\n                    amplification, focusing on its role in shaping the tumor microenvironment (TME). We conducted an\n                    <jats:italic toggle=\"yes\">in silico<\/jats:italic>\n                    analysis utilizing exome sequencing, clinical, and transcriptome data from HGSOC patients available in The Cancer Genome Atlas.\n                    <jats:italic toggle=\"yes\">CCNE1<\/jats:italic>\n                    amplification correlates with significantly reduced overall and disease-free survival in HGSOC patients. Differential gene expression and pathway analyses predicted that\n                    <jats:italic toggle=\"yes\">CCNE1<\/jats:italic>\n                    -amplified tumors associate with replication stress, elevated mitotic activity, and increased chromosomal instability. Importantly, these tumors showed a predicted reprogrammed immune landscape, characterized by elevated stromal content, increased infiltration of M2 macrophages, myeloid-derived suppressor cells, and cancer-associated fibroblasts, alongside reduced expression of antigen-presenting machinery, particularly Human Leukocyte Antigen (HLA) class II genes. Further analysis highlighted a strong association between replication stress and upregulation of Transforming Growth Factor-beta (TGF-\u03b2) signaling pathways, which likely contribute to the observed immunosuppressive microenvironment. Together, our data suggested that\n                    <jats:italic toggle=\"yes\">CCNE1<\/jats:italic>\n                    amplification is associated with tumor progression not only through enhanced proliferation but also by adopting an immune-suppressive TME. These observations suggest the potential of targeting the TME or replication stress response pathways in\n                    <jats:italic toggle=\"yes\">CCNE1<\/jats:italic>\n                    -amplified HGSOC as a therapeutic strategy to improve patient outcomes.\n                  <\/jats:p>","DOI":"10.1177\/15578100261495840","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T05:29:43Z","timestamp":1791437383000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Genomic Amplification of\n                    <i>CCNE1<\/i>\n                    Is Associated with an Immunosuppressive Tumor Microenvironment and Adverse Clinical Outcome in High-Grade Serous Ovarian Cancer"],"prefix":"10.1177","author":[{"given":"Annapurna","family":"Vadaparty","sequence":"first","affiliation":[{"name":"Centre for Doctoral Studies, Manipal Academy of Higher Education, Manipal, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Durgadevi","family":"Veeraiyan","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology, Sri Shankara National Centre for Cancer Prevention and Research, Bangalore, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4998-9636","authenticated-orcid":false,"given":"Guruguhan","family":"Sivakumar","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology, Sri Shankara National Centre for Cancer Prevention and Research, Bangalore, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soumyabrata","family":"Roy","sequence":"additional","affiliation":[{"name":"School of Biosciences, JIS University, Kolkata, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akhileshwar","family":"Namani","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology, Sri Shankara National Centre for Cancer Prevention and Research, Bangalore, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3388-1719","authenticated-orcid":false,"given":"Tapas","family":"Patra","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology, Sri Shankara National Centre for Cancer Prevention and Research, Bangalore, 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