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化疗引起的微小RNA表达改变及其在卵巢癌中的预后意义。

Chemotherapy-induced alterations in miRNA expression and their prognostic implications in ovarian cancer.

作者信息

Ranmale Samruddhi, Kumar Pavan, Tongaonkar Hemant, Mehta Sanket, Maniar Vashishth, Mania-Pramanik Jayanti

机构信息

Department of Infectious Biology, ICMR-National Institute for Research in Reproductive and Child Health, Mumbai, India.

Urologic and Gynecologic Oncology Department, P. D. Hinduja Hospital and Medical Research Centre, Mumbai, Maharashtra, India.

出版信息

Front Oncol. 2025 Aug 22;15:1580565. doi: 10.3389/fonc.2025.1580565. eCollection 2025.

DOI:10.3389/fonc.2025.1580565
PMID:40919157
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12411204/
Abstract

INTRODUCTION

Ovarian cancer has a high mortality rate due to late diagnosis, relapse and chemoresistance. miRNAs play a major role in tumorigenesis as well as chemoresistance. Hence, we undertook a study, to evaluate the differential expression of miRNAs in clinical specimens of ovarian cancer patients that may highlight the effect of chemotherapy and their role in predicting survival outcomes.

METHODS

Clinical specimens were collected from n=127 participants comprising chemo-naive, chemo-treated ovarian cancer patients and healthy women as controls for the study. miRNA expression was evaluated by quantitative real-time PCR analysis.

RESULTS

Our results indicate an upregulation of miR-182 and miR-130a in the serum of treated ovarian cancer patients, which may be an effect of chemotherapy. Tissue levels of miR-182 and miR-106a were elevated in patients with advanced-stage disease. Elevated tissue expression of miR-106a was also associated with poor chemotherapy response and early relapse, while miR-200a was elevated in metastatic patients and linked to early relapse. However, reduced tumor suppressor miR-433 and miR-145 levels were observed in metastatic patients. Multivariate Cox regression identified serum miR-130a and tissue miR-20a as independent predictors of progression-free survival. A combined serum miRNA panel (miR-182, miR-106a, miR-23b) demonstrated diagnostic potential with an AUC of 0.743.

CONCLUSION

The study highlights differential regulation of circulating and tissue miRNAs in Indian OC patients, emphasizing the selective retention of oncogenic miRNAs in tumors and release of tumor suppressive miRNAs into circulation. These findings support the utility of miRNAs as diagnostic and prognostic biomarkers in OC.

摘要

引言

由于诊断延迟、复发和化疗耐药,卵巢癌死亡率很高。微小RNA(miRNA)在肿瘤发生以及化疗耐药中起主要作用。因此,我们开展了一项研究,以评估miRNA在卵巢癌患者临床标本中的差异表达,这可能突出化疗的效果及其在预测生存结果中的作用。

方法

从127名参与者收集临床标本,包括未经化疗、接受过化疗的卵巢癌患者以及作为对照的健康女性。通过定量实时聚合酶链反应分析评估miRNA表达。

结果

我们的结果表明,接受治疗的卵巢癌患者血清中miR-182和miR-130a上调,这可能是化疗的作用。晚期疾病患者组织中miR-182和miR-106a水平升高。miR-106a组织表达升高也与化疗反应差和早期复发相关,而miR-200a在转移患者中升高并与早期复发有关。然而,在转移患者中观察到肿瘤抑制性miR-433和miR-145水平降低。多变量Cox回归确定血清miR-130a和组织miR-20a为无进展生存的独立预测因子。一个联合血清miRNA组合(miR-182、miR-106a、miR-23b)显示出诊断潜力,曲线下面积为0.743。

结论

该研究突出了印度卵巢癌患者循环和组织miRNA的差异调节,强调致癌性miRNA在肿瘤中的选择性保留以及肿瘤抑制性miRNA释放到循环中。这些发现支持miRNA作为卵巢癌诊断和预后生物标志物的实用性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81b6/12411204/1f603195cd51/fonc-15-1580565-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81b6/12411204/f0880cb1e99b/fonc-15-1580565-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81b6/12411204/46412eb59437/fonc-15-1580565-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81b6/12411204/53ea6abc47e2/fonc-15-1580565-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81b6/12411204/1f603195cd51/fonc-15-1580565-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81b6/12411204/f0880cb1e99b/fonc-15-1580565-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81b6/12411204/075a3e4d5f66/fonc-15-1580565-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81b6/12411204/46412eb59437/fonc-15-1580565-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81b6/12411204/1f603195cd51/fonc-15-1580565-g005.jpg

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