Amity Institute of Molecular Medicine & Stem Cell Research (AIMMSCR), Amity University Campus, Sector-125, Noida, Uttar Pradesh, 201313, India.
Department of Gynecology and Obstetrics, Safdarjung Hospital, New Delhi, 110029, India.
Sci Rep. 2021 May 14;11(1):10323. doi: 10.1038/s41598-021-89388-w.
MicroRNAs as cancer biomarkers in serum, plasma, and other body fluids are often used but analysis of miRNA in urine is limited. We investigated the expression of selected miRNAs in the paired urine, serum, cervical scrape, and tumor tissue specimens from the women with cervical precancer and cancer with a view to identify if urine miRNAs could be used as reliable non-invasive biomarkers for an early diagnosis and prognosis of cervical cancer. Expression of three oncomiRs (miR-21, miR-199a, and miR-155-5p) and three tumor suppressors (miR-34a, miR-145, and miR-218) as selected by database search in cervical pre-cancer, cancer, and normal controls including cervical cancer cell lines were analyzed using qRT-PCR. The expression of miRNAs was correlated with various clinicopathological parameters, including HPV infection and survival outcome. We observed a significant overexpression of the oncomiRs and the downregulation of tumor suppressor miRNAs. A combination of miR-145-5p, miR-218-5p, and miR-34a-5p in urine yielded 100% sensitivity and 92.8% specificity in distinguishing precancer and cancer patients from healthy controls and it well correlates with those of serum and tumor tissues. The expression of miR-34a-5p and miR-218-5p were found to be independent prognostic factors for the overall survival of cervical cancer patients. We conclude that the evaluation of the above specific miRNA expression in non-invasive urine samples may serve as a reliable biomarker for early detection and prognosis of cervical cancer.
微 RNA 作为血清、血浆和其他体液中的癌症生物标志物经常被使用，但尿液中 miRNA 的分析受到限制。我们研究了具有宫颈癌前病变和癌症的女性配对尿液、血清、宫颈刮片和肿瘤组织标本中选定的 miRNA 的表达，以期确定尿液 miRNA 是否可以作为宫颈癌早期诊断和预后的可靠非侵入性生物标志物。通过数据库搜索在宫颈癌前病变、癌症和正常对照（包括宫颈癌细胞系）中选择的三个癌基因（miR-21、miR-199a 和 miR-155-5p）和三个肿瘤抑制因子（miR-34a、miR-145 和 miR-218）的表达使用 qRT-PCR 进行分析。miRNA 的表达与包括 HPV 感染和生存结果在内的各种临床病理参数相关。我们观察到癌基因的表达显著上调和肿瘤抑制因子 miRNA 的下调。miR-145-5p、miR-218-5p 和 miR-34a-5p 的组合在区分宫颈癌前病变和癌症患者与健康对照者方面具有 100%的敏感性和 92.8%的特异性，并且与血清和肿瘤组织的相关性良好。miR-34a-5p 和 miR-218-5p 的表达被发现是宫颈癌患者总生存的独立预后因素。我们得出结论，评估非侵入性尿液样本中上述特定 miRNA 的表达可能是宫颈癌早期检测和预后的可靠生物标志物。
