Department of Molecular Biology and Genetics, Faculty of Science and Arts, Tokat Gaziosmanpasa University, Tokat, 60250, Turkey.
Hum Cell. 2021 May;34(3):862-877. doi: 10.1007/s13577-021-00486-3. Epub 2021 Feb 12.
Ovarian cancer (OC) is the most lethal gynecological malignancy and cellular mechanisms regulating OC progression are not completely understood. miRNAs are involved in many signaling pathways which are critical for the progression of malignant tumors, including OC. In the present study, we aim to identify miRNAs whose expression change in a tumor stage- and/or grade-dependent manner in serous OC. Computational analysis was performed in R using The Cancer Genome Atlas miRNA dataset. Kaplan-Meier plots were constructed to compare the survival of patients with low and high expressions of identified miRNAs. We found that 91 and 90 miRNAs out of 799 are differentially expressed in terms of tumor stage and grade, respectively. miR-152, miR-375 and miR-204 were top three hits in terms of tumor stage; and similarly, miR-125b, miR-768-5p and -3p in terms of tumor grade. Among top 15 miRNAs whose expression most significantly changed between tumor stages, 66.7% were upregulated in late stage. However, 53.3% of top 15 miRNAs identified in terms of tumor grade were upregulated in high grade. 11 miRNAs are differentially expressed in terms of both tumor stage and grade. Expression changes of some of the top miRNAs were found to be associated with shorter survival in serous OC. Text mining analysis showed that most of these miRNAs have not been previously studied in the context of OC. Mechanistic studies of these miRNAs in OC progression, differentiation and metastasis will be of high importance to develop novel strategies for the treatment of serous ovarian cancer.
卵巢癌 (OC) 是最致命的妇科恶性肿瘤，其调控机制尚不完全清楚。miRNA 参与了许多信号通路，这些信号通路对恶性肿瘤的进展至关重要，包括 OC。在本研究中，我们旨在鉴定在浆液性 OC 中以肿瘤分期和/或分级依赖方式表达变化的 miRNA。使用 The Cancer Genome Atlas miRNA 数据集在 R 中进行计算分析。构建 Kaplan-Meier 图比较低表达和高表达鉴定 miRNA 的患者的生存情况。我们发现，在肿瘤分期和分级方面，799 个 miRNA 中有 91 个和 90 个分别差异表达。miR-152、miR-375 和 miR-204 在肿瘤分期方面排名前三；miR-125b、miR-768-5p 和 -3p 在肿瘤分级方面排名相同。在肿瘤分期之间表达变化最显著的前 15 个 miRNA 中，有 66.7%在晚期上调。然而，在肿瘤分级方面，前 15 个 miRNA 中有 53.3%在高级别上调。有 11 个 miRNA 在肿瘤分期和分级方面均有差异表达。一些顶级 miRNA 的表达变化与浆液性 OC 患者的生存时间缩短有关。文本挖掘分析表明，这些 miRNA 中的大多数以前尚未在 OC 背景下进行研究。这些 miRNA 在 OC 进展、分化和转移中的机制研究对于开发治疗浆液性卵巢癌的新策略具有重要意义。
