Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2021 May 14;11(1):10323.
doi: 10.1038/s41598-021-89388-w.

Urine miRNA signature as a potential non-invasive diagnostic and prognostic biomarker in cervical cancer

Mehreen Aftab  1 , Satish S Poojary  1 , Vaishnavi Seshan  2 , Sachin Kumar  3 , Pallavi Agarwal  1 , Simran Tandon  1 , Vijay Zutshi  2 , Bhudev C Das  4
Affiliations
Observational Study

Urine miRNA signature as a potential non-invasive diagnostic and prognostic biomarker in cervical cancer

Mehreen Aftab et al. Sci Rep. .

Abstract

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.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Comparative differential expression profile of six miRNAs in urine, serum, tissue biopsies and cervical scrape derived from healthy controls, cancer and pre-cancer. (a & c) The miRNA expression level of upregulated miRNAs (miR-21-5p, miR-155-5p, miR-199a-5p) and (b & d) down regulated miRNAs (miR-145-5p, miR218-5p, and miR-34a-5p). Urine and serum samples were taken from pre-cancer and cervical cancer patients and compared to samples from healthy controls. In case of tissue biopsies, the samples are derived from cancer patients compared with samples from adjacent non-malignant normal tissues. **P ≤ 0.01, ns (nonsignificant), while in case of cervical scrape, the samples are derived from pre-cancer patients and compared with samples from healthy volunteers.
Figure 2
Figure 2
Expression levels of miR-21-5p, miR-155-5p, miR-199a-5p, miR-145-5p, miR-218-5p, and miR-34a-5p in HPV16-positive (a & c) and HPV16-negative (b & d) urine, serum, and cervical scrape samples of cervical pre-cancer and in HPV16-positive (e & g) and HPV16-negative (f & h) urine, serum, and tissue biopsies of cervical cancer patients.
Figure 3
Figure 3
Receiver operating characteristics (ROC) plots of miRNA expression in urine sample of cervical cancer patients. ROC plots evaluating diagnostic potential of (a) miR-21-5p, (b) miR-155-5p, (c) miR-199a-5p, (d) combined ROC plots of three upregulated miRNAs (miR-21-5p, miR-155-5p, and miR-199a-5p), (e) miR-218-5p, (f) miR-145-5p, (g) miR-34a-5p, (h) combined ROC plots of three downregulated miRNAs (miR-218-5p, miR34a-5p, and miR-145-5p), and (l) combined ROC plots of all six miRNAs.
Figure 4
Figure 4
The correlation of miRNA expression with overall survival of cervical cancer patients calculated using Kaplan Meier curve and Log-rank test. The patients were stratified into high expression and low expression group according to median of each miRNA. (a) miR-21-5p, (b) miR-199a-5p, (c) miR-155-5p, (d) miR-218-5p, (e) miR-145-5p, (f) miR-34a-5p, (g) three upregulated miRNA signatures, and (h) three downregulated miRNA signatures. The patients were stratified into high-risk group and low risk group based on median.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2018;68(6):394–424. doi: 10.3322/caac.21492. - DOI - PubMed
    1. WHO | Human papillomavirus (HPV). WHO. 2018.
    1. Rodríguez AC, Schiffman M, Herrero R, et al. Rapid clearance of human papillomavirus and implications for clinical focus on persistent infections. J. Natl. Cancer Inst. 2008;100(7):513–517. doi: 10.1093/jnci/djn044. - DOI - PMC - PubMed
    1. Jm W, Mv J, Mm M, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J. Pathol. 1999;189(1):159. - PubMed
    1. Montgomery MP, Dune T, Shetty PK, Shetty AK. Knowledge and acceptability of human papillomavirus vaccination and cervical cancer screening among women in Karnataka India. J. Cancer Educ. 2015;30(1):130–137. doi: 10.1007/s13187-014-0745-4. - DOI - PubMed

Publication types

MeSH terms

-