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Clin. Cancer Res., May 13 2025, | https://doi.org/10.1158/1078-0432.CCR-24-4263
Genomic Profiling in Patients with Endometrial Cancer by Deep Sequencing of Vaginal Swabs and Plasma
Namsoo Kim1,2†, Yoo-Na Kim3†, Kyunglim Lee3, Eunhyang Park4, Yong Jae Lee3, Eunha Baek5, Seungki Min5, Jihyang Park5, Zisun Choi5, Saeam Shin1, Sang Wun Kim3, Sunghoon Kim3, Jong Rak Choi1,5, Seung-Tae Lee1,5*‡, Jung-Yun Lee3*‡
1Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
2Aerospace Medical Center, Republic of Korea Air Force, Cheongju, Republic of Korea
3Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul, Republic of Korea
4Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea
5Dxome Co., Ltd., Seongnam, Republic of Korea
*Correspondence: Seung-Tae Lee, Jung-Yun Lee
†These authors contributed equally to this work and share first authorship.
‡These authors contributed equally to this work and share last authorship.
1Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
2Aerospace Medical Center, Republic of Korea Air Force, Cheongju, Republic of Korea
3Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul, Republic of Korea
4Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea
5Dxome Co., Ltd., Seongnam, Republic of Korea
*Correspondence: Seung-Tae Lee, Jung-Yun Lee
†These authors contributed equally to this work and share first authorship.
‡These authors contributed equally to this work and share last authorship.
Abstract
Introduction: Endometrial cancer is a common gynecologic malignancy lacks effective non-invasive screening tools, as traditional approaches rely on invasive biopsies. In this large prospective study, we evaluated a novel approach combining vaginal swab DNA and plasma-based circulating tumor DNA (ctDNA) for genomic profiling to provide a comprehensive framework for diagnosis, prognosis, and disease monitoring.
Materials and methods: Adult patients with diverse stages of endometrial cancer, pre-neoplastic disease, and benign endometrial conditions were prospectively recruited over two years. Paired vaginal swab DNA and plasma-based ctDNA were collected pre-operatively, and additional plasma samples were obtained multiple time points post-operatively. Deep next-generation sequencing targeting 101 genes was performed, achieving an average depth exceeding 40,000x.
Results: A total of 191 patients contributed 388 samples. Vaginal swab DNA demonstrated 77.7% sensitivity and 96.6% specificity. PTEN mutations were associated with favorable prognosis (hazard ratio: 0.27; 95% CI: 0.092-0.77) and TP53 mutations were associated with poor prognosis (hazard ratio: 3.7; 95% CI: 1.4-10). A novel classification system based on the mutational profile of PTEN/TP53 identified distinct prognostic groups. Plasma-based ctDNA was significantly associated with stage, lymphovascular invasion, and prognosis (p < 0.01 for all). Patients with pre-operative positive plasma-based ctDNA results exhibited poorer outcomes (p < 0.01), whereas post-operative positive ctDNA enabled early detection of recurrence.
Discussion: These two non-invasive methods have distinct, complementary roles in the management of endometrial cancer. Vaginal swab DNA and novel PTEN/TP53-based classification have distinct prognostic advantages over existing frameworks. Plasma-based ctDNA provides dynamic insights into recurrence risk and disease progression.
Materials and methods: Adult patients with diverse stages of endometrial cancer, pre-neoplastic disease, and benign endometrial conditions were prospectively recruited over two years. Paired vaginal swab DNA and plasma-based ctDNA were collected pre-operatively, and additional plasma samples were obtained multiple time points post-operatively. Deep next-generation sequencing targeting 101 genes was performed, achieving an average depth exceeding 40,000x.
Results: A total of 191 patients contributed 388 samples. Vaginal swab DNA demonstrated 77.7% sensitivity and 96.6% specificity. PTEN mutations were associated with favorable prognosis (hazard ratio: 0.27; 95% CI: 0.092-0.77) and TP53 mutations were associated with poor prognosis (hazard ratio: 3.7; 95% CI: 1.4-10). A novel classification system based on the mutational profile of PTEN/TP53 identified distinct prognostic groups. Plasma-based ctDNA was significantly associated with stage, lymphovascular invasion, and prognosis (p < 0.01 for all). Patients with pre-operative positive plasma-based ctDNA results exhibited poorer outcomes (p < 0.01), whereas post-operative positive ctDNA enabled early detection of recurrence.
Discussion: These two non-invasive methods have distinct, complementary roles in the management of endometrial cancer. Vaginal swab DNA and novel PTEN/TP53-based classification have distinct prognostic advantages over existing frameworks. Plasma-based ctDNA provides dynamic insights into recurrence risk and disease progression.
논문정보
- Research article
- 2025년 05월 (BRIC 등록일 2025-05-14)
- 국내 연구진
- 의약학 > 유전 및 유전체의학
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