LINE-1开放阅读框1蛋白（ORF1p）表达出现在卵巢透明细胞癌前体中，是一种潜在的血液生物标志物。

LINE-1 ORF1p expression occurs in clear cell ovarian carcinoma precursors and is a candidate blood biomarker.

作者信息

de Santiago Pamela R, Sato Sho, Zhang Stephanie J, Dougher Meaghan C, Devins Kyle M, Bilecz Agnes J, Rayamajhi Sagar, Mingo Gabriel, Rendulich Hannah S, Feng Yi, Wu Connie, Taylor Martin S, Zhuravlev Yelena, Jung Euihye, Omran Dalia K, Wang Tian-Li, Shih Ie-Ming, Schwartz Lauren E, Kim Sarah, Morgan Mark A, Tanyi Janos L, Burns Kathleen H, Lengyel Ernst, Parra-Herran Carlos, Godwin Andrew K, Walt David R, Drapkin Ronny

机构信息

Penn Ovarian Cancer Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

出版信息

NPJ Precis Oncol. 2025 Mar 6;9(1):62. doi: 10.1038/s41698-025-00849-1.

DOI:10.1038/s41698-025-00849-1

PMID:40050409

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11885553/

Abstract

Long interspersed element 1 (LINE-1) retrotransposons are repetitive sequences that can move within the genome by an autonomous mechanism. To limit their mutagenic potential, benign cells restrict LINE-1 expression through molecular mechanisms such as DNA methylation and histone modification, but these mechanisms are usually impaired in cancer. Clear cell ovarian carcinoma (CCOC) represents 5-10% of ovarian cancers and is thought to arise from endometriosis. Women with advanced CCOC face poor prognoses, highlighting the importance of understanding early disease pathogenesis. In our study, 33 of 40 cases (over 82%) of CCOC tumors express ORF1p, a LINE-1-encoded protein. We found that LINE-1 de-repression is an early event in CCOC, as ORF1p is enhanced during the transition from typical to atypical endometriosis and persists in invasive cancer. Finally, using single-molecule array (Simoa) assays, we detected ORF1p in patient blood, suggesting it as a potential minimally invasive biomarker for this disease.

摘要

长散在元件1（LINE-1）逆转座子是可通过自主机制在基因组内移动的重复序列。为限制其诱变潜力，良性细胞通过DNA甲基化和组蛋白修饰等分子机制限制LINE-1表达，但这些机制在癌症中通常受损。透明细胞卵巢癌（CCOC）占卵巢癌的5%-10%，被认为起源于子宫内膜异位症。晚期CCOC患者预后较差，这凸显了了解疾病早期发病机制的重要性。在我们的研究中，40例CCOC肿瘤中有33例（超过82%）表达ORF1p，这是一种由LINE-1编码的蛋白质。我们发现，LINE-1去抑制是CCOC中的一个早期事件，因为在从典型子宫内膜异位症向非典型子宫内膜异位症转变过程中ORF1p表达增强，并在浸润性癌中持续存在。最后，我们使用单分子阵列（Simoa）检测法在患者血液中检测到了ORF1p，表明它可能是这种疾病的一种潜在微创生物标志物。