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

IF 3.4 3区 生物学 Q3 CELL BIOLOGY
Chenyang Xu, Weiming Xu, Conghui Wu, Chen Xu, Zhengxiao Ma, Jiamin Wang, Yue Zhuo, Xinan Cai, Yuting Zhang, Yingqi Lyu, Jinchao Wang, Minran Huang, Shu Sun, Tingting Feng, Lisha Ying, Dan Su
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引用次数: 0

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.

原发性卵巢鳞状细胞癌临床前模型的建立与表征。
原发性卵巢鳞状细胞癌(POSCC)是一种非常罕见的上皮性卵巢癌(EOC)亚型,其特点是病因不明,发病隐匿。单纯原发性卵巢鳞状细胞癌(SCC)的罕见性和高死亡率使得进行大型随机对照研究具有挑战性。此外,目前还没有商业上可用的用于研究目的的卵巢SCC细胞系,迫切需要建立新的细胞系。据我们所知,本研究报告了第一个原发性卵巢鳞状细胞癌(POSCC)的临床前模型,标记为ZOC254。我们详细描述了ZOC254的建立和特征,该基因来源于一名64岁的女性患者,在长时间的体外扩增过程中,它在不同水平上保留了原发肿瘤的原始特征。原发肿瘤和衍生细胞系的全外显子组测序(WES)显示同源重组缺陷(HRD)和高肿瘤突变负担(TMB)。ZOC254还表现出与靶向治疗相关的PIK3CA: p.E542K突变。奥拉帕尼、依维莫司和常规化疗药物治疗卵巢癌的有效性通过患者源性细胞(PDC)的生长进行初步评估。本研究报道的POSCC细胞系和衍生的异种移植移植模型的目的是拓宽卵巢癌临床前研究的资源。
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来源期刊
Human Cell
Human Cell CELL BIOLOGY-
CiteScore
5.90
自引率
2.30%
发文量
176
审稿时长
4.5 months
期刊介绍: Human Cell is the official English-language journal of the Japan Human Cell Society. The journal serves as a forum for international research on all aspects of the human cell, encompassing not only cell biology but also pathology, cytology, and oncology, including clinical oncology. Embryonic stem cells derived from animals, regenerative medicine using animal cells, and experimental animal models with implications for human diseases are covered as well. Submissions in any of the following categories will be considered: Research Articles, Cell Lines, Rapid Communications, Reviews, and Letters to the Editor. A brief clinical case report focusing on cellular responses to pathological insults in human studies may also be submitted as a Letter to the Editor in a concise and short format. Not only basic scientists but also gynecologists, oncologists, and other clinical scientists are welcome to submit work expressing new ideas or research using human cells.
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