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原发性卵巢鳞状细胞癌临床前模型的建立与特性分析

Establishment and characterization of preclinical model of primary ovarian squamous cell carcinoma.

作者信息

Xu Chenyang, Xu Weiming, Wu Conghui, Xu Chen, Ma Zhengxiao, Wang Jiamin, Zhuo Yue, Cai Xinan, Zhang Yuting, Lyu Yingqi, Wang Jinchao, Huang Minran, Sun Shu, Feng Tingting, Ying Lisha, Su Dan

机构信息

Postgraduate Training Base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital), Hangzhou, 310022, Zhejiang, China.

Department of Pathology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, Zhejiang, China.

出版信息

Hum Cell. 2025 Jul 7;38(5):125. doi: 10.1007/s13577-025-01253-4.

Abstract

Primary ovarian squamous cell carcinoma (POSCC) represents an exceedingly rare subtype of epithelial ovarian cancer (EOC) characterized by a cryptic etiology and insidious onset. The rarity and high mortality associated with pure primary ovarian squamous cell carcinoma (SCC) make it challenging to conduct large randomized controlled studies. Furthermore, there are currently no commercially available ovarian SCC cell lines for research purposes, necessitating the urgent establishment of novel lines. To our knowledge, this study reports the first preclinical model of primary ovarian squamous cell carcinoma (POSCC), denoted as ZOC254. We have detailed the establishment and characterization of ZOC254, derived from a 64-year-old female patient, which preserves the primary tumor's original traits across various levels during prolonged in vitro expansion. Whole-exome sequencing (WES) of both the primary tumor and derived cell line revealed homologous recombination deficiency (HRD) and high tumor mutational burden (TMB). ZOC254 also exhibited the PIK3CA: p.E542K mutation associated with targeted therapy. The effectiveness of olaparib, everolimus, and conventional chemotherapeutic agents for ovarian cancer was preliminarily assessed on the growth of patient-derived cells (PDC). The POSCC cell line and derived xenograft transplantation model reported in this study serve the purpose of broadening the resources accessible for preclinical investigations into ovarian squamous carcinoma.

摘要

原发性卵巢鳞状细胞癌(POSCC)是上皮性卵巢癌(EOC)中一种极为罕见的亚型,其病因隐匿,起病隐匿。纯原发性卵巢鳞状细胞癌(SCC)的罕见性和高死亡率使得开展大型随机对照研究具有挑战性。此外,目前尚无用于研究目的的商业化卵巢SCC细胞系,因此迫切需要建立新的细胞系。据我们所知,本研究报告了首个原发性卵巢鳞状细胞癌(POSCC)的临床前模型,命名为ZOC254。我们详细介绍了ZOC254的建立和特征,该细胞系源自一名64岁女性患者,在长时间体外传代培养过程中,在各个水平上都保留了原发性肿瘤的原始特征。对原发性肿瘤和衍生细胞系进行全外显子测序(WES),结果显示存在同源重组缺陷(HRD)和高肿瘤突变负荷(TMB)。ZOC254还表现出与靶向治疗相关的PIK3CA:p.E542K突变。我们初步评估了奥拉帕利、依维莫司和传统化疗药物对患者来源细胞(PDC)生长的有效性。本研究报道的POSCC细胞系和衍生的异种移植模型,旨在拓宽用于卵巢鳞状癌临床前研究的资源。

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