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Oncogenic microRNA signature for early diagnosis of cervical intraepithelial neoplasia and cancer.

ABSTRACT: Cervical cancer is one of the leading causes of cancer death in women globally, despite the widespread use of cytology/human papillomavirus (HPV) screening. In the present study, we aimed to identify the potential role of microRNA (miRNA) as a diagnostic biomarker in the detection of cervical pre-malignant lesions and cancer. In total, we recruited 582 patients with cervical diseases and 145 control individuals. The expression levels of six miRNAs (miR-20a, miR-92a, miR-141, miR-183*, miR-210 and miR-944) were found to be significantly up-regulated in cervical cancer and pre-malignant lesions compared to normal cervical samples, indicating that they are oncogenic miRNAs. Receiver operating characteristic curve analysis showed that these six miRNAs can be used to distinguish patients with cervical pre-malignant lesions or cancer from normal individuals and they also had a good predictive performance, particularly in cervical lesions. Combined use of these six miRNAs further enhanced the diagnostic accuracy over any single miRNA marker, with an area under the curve of 0.998, 0.996 and 0.959, a diagnostic sensitivity of 97.9%, 97.2% and 91.4%, and a specificity of 98.6%, 96.6% and 87.6% for low-grade lesions, high-grade lesions and cancer, respectively. This six oncogenic miRNA signature may be suitable for use as diagnostic marker for cervical pre-malignant lesions and cancer in the near future.

SUBMITTER: Liu SS

PROVIDER: S-EPMC6275249 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Oncogenic microRNA signature for early diagnosis of cervical intraepithelial neoplasia and cancer.

Liu Stephanie S SS Chan Karen K L KKL Chu Daniel K H DKH Wei Tina N TN Lau Lesley S K LSK Ngu Siew F SF Chu Mandy M Y MMY Tse Ka Yu KY Ip Philip P C PPC Ng Enders K O EKO Cheung Annie N Y ANY Ngan Hextan Y S HYS

Molecular oncology 20180927 12

Cervical cancer is one of the leading causes of cancer death in women globally, despite the widespread use of cytology/human papillomavirus (HPV) screening. In the present study, we aimed to identify the potential role of microRNA (miRNA) as a diagnostic biomarker in the detection of cervical pre-malignant lesions and cancer. In total, we recruited 582 patients with cervical diseases and 145 control individuals. The expression levels of six miRNAs (miR-20a, miR-92a, miR-141, miR-183*, miR-210 an ...[more]

PMID: 30221475

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Project description:New prevention strategies are needed to detect cervical intraepithelial neoplasia (CIN). The microRNA expression analysis has already been reported as molecular biomarkers in the early detection of cervical cancer (CC) through minimally invasive samples, such as liquid biopsy, obtained through collection using liquid-based cytology (LBC). In this study, we aimed to identify molecular signatures of microRNAs in cervical precursor lesions from LBC cervical and the molecular pathways potentially associated with the CC progression. We analyzed 31 LBC cervical samples from women who underwent colposcopy. These samples were divided into two groups: the first group was composed of samples without precursor lesions of CC, considering the control group, referred to as healthy female subjects (HFS; n = 11). The second group corresponded to women diagnosed with cervical interepithelial neoplasia grade 3 (CIN 3; n = 20). We performed microRNA and gene expression profiling using the nCounter® miRNA Expression Assays (NanoString Technology) and PanCancer Pathways (NanoString Technology), respectively. A microRNA target prediction was performed by mirDIP, and molecular pathway interaction was constructed using Cytoscape. Bidirectional in silico analyses and Pearson's correlation were performed for associated the relation between genes, and miRNAs differentially expressed related cervical cancer progression were performed. We found that the expression of nine microRNAs was significantly higher, two were downregulated (miR-381-3p and miR-4531), and seven miRNAs were upregulated (miR-205-5p, miR-130a-3p, miR-3136-3p, miR-128-2-5p, let-7f-5p, miR-202-3p, and miR-323a-5p) in CIN 3 (fold change ≥ 2 and p ≤ 0.05). The miRNA expression patterns were independent of hr-HPV infection. We identified four miRNAs (miR-205-5p, miR-130a-3p, miR-4531, and miR-381-3p) that could be used as biomarkers for CIN 3 in LBC samples through multiple logistic regression analyses. We found 16 genes differentially expressed between CIN 3 and HSF samples (fold change ≥ 2 and p ≤ 0.05). We found the correlation between miR-130a-3p and CCND1(R = -0.52; p = 0.0029), miR-205-5p and EGFR (R = 0.53; p = 0.0021), and miR-4531 and SMAD2 (R = -0.54; p = 0.0016). In addition, we demonstrated the most significant pathways of the targets associated with cervical cancer progression (FDR-corrected p < 0.001). This study demonstrated that miRNA biomarkers may distinguish healthy cervix and CIN 3 and regulate important molecular pathways of carcinogenesis.

Dataset Information

Oncogenic microRNA signature for early diagnosis of cervical intraepithelial neoplasia and cancer.

Publications

Oncogenic microRNA signature for early diagnosis of cervical intraepithelial neoplasia and cancer.

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