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AhRR 和 PPP1R3C:浆液性卵巢癌的潜在预后生物标志物。

AhRR and PPP1R3C: Potential Prognostic Biomarkers for Serous Ovarian Cancer.

机构信息

School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy.

出版信息

Int J Mol Sci. 2023 Jul 14;24(14):11455. doi: 10.3390/ijms241411455.

Abstract

The lack of effective screening and successful treatment contributes to high ovarian cancer mortality, making it the second most common cause of gynecologic cancer death. Development of chemoresistance in up to 75% of patients is the cause of a poor treatment response and reduced survival. Therefore, identifying potential and effective biomarkers for its diagnosis and prognosis is a strong critical need. Copy number alterations are frequent in cancer, and relevant for molecular tumor stratification and patients' prognoses. In this study, array-CGH analysis was performed in three cell lines and derived cancer stem cells (CSCs) to identify genes potentially predictive for ovarian cancer patients' prognoses. Bioinformatic analyses of genes involved in copy number gains revealed that AhRR and PPP1R3C expression negatively correlated with ovarian cancer patients' overall and progression-free survival. These results, together with a significant association between AhRR and PPP1R3C expression and ovarian cancer stemness markers, suggested their potential role in CSCs. Furthermore, AhRR and PPP1R3C's increased expression was maintained in some CSC subpopulations, reinforcing their potential role in ovarian cancer. In conclusion, we reported for the first time, to the best of our knowledge, a prognostic role of AhRR and PPP1R3C expression in serous ovarian cancer.

摘要

缺乏有效的筛查和成功的治疗导致卵巢癌死亡率居高不下,使其成为妇科癌症死亡的第二大常见原因。多达 75%的患者出现化疗耐药是治疗反应不佳和存活率降低的原因。因此,寻找潜在的有效生物标志物用于其诊断和预后是一个强烈的迫切需求。拷贝数改变在癌症中很常见,与分子肿瘤分层和患者预后相关。在这项研究中,对三个细胞系和衍生的癌症干细胞 (CSC) 进行了 array-CGH 分析,以确定可能预测卵巢癌患者预后的基因。涉及拷贝数增益的基因的生物信息学分析表明,AhRR 和 PPP1R3C 的表达与卵巢癌患者的总生存期和无进展生存期呈负相关。这些结果,以及 AhRR 和 PPP1R3C 表达与卵巢癌干细胞标志物之间的显著关联,表明它们在 CSC 中可能具有作用。此外,AhRR 和 PPP1R3C 的表达增加在一些 CSC 亚群中得到维持,进一步证实了它们在卵巢癌中的潜在作用。总之,据我们所知,这是首次报道 AhRR 和 PPP1R3C 表达在浆液性卵巢癌中的预后作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c5b/10380391/59e4274ee6de/ijms-24-11455-g001.jpg

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