Abstract

Despite the fact that the incidence of cervical squamous cell carcinoma has decreased, there is an increase in the incidence of cervical adenocarcinoma. However, our knowledge on cervical adenocarcinoma is largely unclear. Transcriptome sequencing was conducted to compare 4 cervical adenocarcinoma tissue samples with 4 normal cervical tissue samples. mRNA, lncRNA, and miRNA signatures were identified to discriminate cervical adenocarcinoma from normal cervix. The expression of VIL1, HNF1A-AS1, MIR194-2HG, SSTR5-AS1, miR-192-5p, and miR-194-5p in adenocarcinoma were statistically significantly higher than that in normal control samples. The Receiver Operating Characteristic (ROC) curve analysis indicated that combination of miR-192-5p, HNF1A-AS1, and VIL1 yielded a better performance (AUC = 0.911) than any single molecule -and could serve as potential biomarkers for cervical adenocarcinoma. Of note, the combination model also gave better performance than TCT test for cervical adenocarcinoma diagnosis. However, there was no correlation between miR-192-5p or HNF1A-AS1 and HPV16/18 E6 or E7. VIL1 was weakly correlated with HPV18 E7 expression. In summary, our study has identified miR-192-5p/HNF1A-AS1/VIL1 panel that accurately discriminates adenocarcinoma from normal cervix. Detection of this panel may provide considerable clinical value in the diagnosis of cervical adenocarcinoma.

Highlights

  • Abbreviations SCC Cervical squamous cell carcinoma NcRNA Non-coding RNA MiRNA MicroRNA LncRNA Long non-coding RNA Receiver Operating Characteristic (ROC) Receiver operating characteristic area under the ROC curve (AUC) Area under the ROC curve RT-qPCR Quantitative reverse-transcriptase PCR HNF1A-AS1 LncRNA HNF1A antisense RNA 1 VIL1 Villin 1

  • We revealed that a panel with miR-192-5p, HNF1A-AS1 and VIL1 could accurately discriminate adenocarcinoma from normal cervix

  • Using the same stringent criteria, a total of 1,711 differentially expressed mRNAs (DEmRNAs), 671 DElncRNAs, and 89 DEmiRNAs were identified from cervical adenocarcinoma compared with normal tissue samples

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Summary

Introduction

Abbreviations SCC Cervical squamous cell carcinoma NcRNA Non-coding RNA MiRNA MicroRNA LncRNA Long non-coding RNA ROC Receiver operating characteristic AUC Area under the ROC curve RT-qPCR Quantitative reverse-transcriptase PCR HNF1A-AS1 LncRNA HNF1A antisense RNA 1 VIL1 Villin 1. The predominant cases are cervical squamous cell carcinoma (SCC), and the second pool (about 10–25%) is cervical ­adenocarcinoma[2,3] The former has been greatly prevented by cytological screening and HPV vaccination in developed countries. High-throughput RNA sequencing technology facilitates the quantification measurements of RNA expression at the entire transcriptome level. These large-scale expression profiles of RNAs enable the detection of protein-coding RNAs (i.e., mRNAs) and non-coding RNAs (i.e., ncRNAs), which could be of profound value in terms of disease characterization. It was reported that the expression of miR-27a is decreased in cervical cancer cell lines and it functions as a tumor suppressor in cervical adenocarcinoma by inhibiting TGF-βRI signaling ­pathway[21]. The lncRNA profile in cervical adenocarcinoma remains largely unknown

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