Department of Obstetrics and Gynecology, Sanggye Paik Hospital, Inje University College of Medicine, Seoul 01757, Republic of Korea.
Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06299, Republic of Korea.
Oncol Rep. 2023 May;49(5). doi: 10.3892/or.2023.8539. Epub 2023 Mar 31.
The vacuolar ATPase H+ transporting V1 subunit B1 (ATP6V1B1) belongs to the family of ATP6Vs, which functions to transport hydrogen ions. The expression of ATP6V1B1 and associated clinicopathological features have been linked to various cancers; however, its role in epithelial ovarian cancer (EOC) has remained to be explored. The present study aimed to unveil the function, molecular mechanisms and clinical significance of ATP6V1B1 in EOC. The mRNA levels of ATP6V1 subunits A, B1 and B2 in EOC tissues were determined using data from the Gene Expression Profiling Interactive Analysis database and RNA sequencing. Protein levels of ATP6V1B1 were evaluated through immunohistochemistry staining of EOC, borderline, benign and normal epithelial tissues. The association between ATP6V1B1 expression and clinicopathological features and prognosis of patients with EOC was analyzed. Furthermore, the biological role of ATP6V1B1 in ovarian cancer cell lines was also assessed. RNA sequencing and public dataset analyses revealed elevated ATP6V1B1 mRNA levels in EOCs. High ATP6V1B1 protein levels were also observed in EOC compared with those of borderline and benign tumors and nonadjacent normal epithelial tissues. High ATP6V1B1 expression was associated with the serous cell type, advanced International Federation of Gynecology and Obstetrics stage, high/advanced tumor grade, elevated serum cancer antigen 125 levels and platinum resistance (P<0.001, P<0.001, P=0.035, P=0.029 and P=0.011, respectively). High expression levels of ATP6V1B1 were also associated with poor overall and disease‑free survival (P<0.001). Knockdown of ATP6V1B1 decreased cancer cell proliferation and colony‑forming abilities (P<0.001) by inducing cell cycle arrest in G0/G1 phase. Significant upregulation of ATP6V1B1 was observed in EOC and the prognostic significance and association with chemotherapy resistance of ATP6V1B1 in EOC was demonstrated, rendering it an EOC‑related biomarker for prognostic evaluation and chemotherapy resistance, as well as a potential therapeutic target for patients with EOC.
液泡型三磷酸腺苷酶 H+ 转运 V1 亚基 B1（ATP6V1B1）属于 ATP6V 家族，其功能是转运氢离子。ATP6V1B1 的表达及其与临床病理特征的关联已与多种癌症相关，但在卵巢上皮性癌（EOC）中的作用仍有待探索。本研究旨在揭示 ATP6V1B1 在 EOC 中的功能、分子机制和临床意义。通过基因表达谱交互分析数据库和 RNA 测序确定 EOC 组织中 ATP6V1 亚基 A、B1 和 B2 的 mRNA 水平。通过对 EOC、交界性、良性和正常上皮组织的免疫组织化学染色评估 ATP6V1B1 的蛋白水平。分析 ATP6V1B1 表达与 EOC 患者临床病理特征和预后的关系。此外，还评估了 ATP6V1B1 在卵巢癌细胞系中的生物学作用。RNA 测序和公共数据集分析显示，EOC 中 ATP6V1B1 的 mRNA 水平升高。与交界性和良性肿瘤以及非相邻正常上皮组织相比，EOC 中 ATP6V1B1 蛋白水平也较高。高 ATP6V1B1 表达与浆液细胞类型、国际妇产科联合会（FIGO）晚期、高级/晚期肿瘤分级、升高的血清癌症抗原 125 水平和铂类耐药相关（P<0.001、P<0.001、P=0.035、P=0.029 和 P=0.011）。高表达水平的 ATP6V1B1 与总生存和无病生存不良相关（P<0.001）。敲低 ATP6V1B1 通过诱导 G0/G1 期细胞周期停滞，降低癌细胞增殖和集落形成能力（P<0.001）。在 EOC 中观察到 ATP6V1B1 的显著上调，并证明了其在 EOC 中的预后意义及其与化疗耐药性的关联，使其成为用于评估预后和化疗耐药性的 EOC 相关生物标志物，以及患者的潜在治疗靶点。EOC。
