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
Review
. 2023 Jan 30;15(3):853.
doi: 10.3390/cancers15030853.

Candidate Genes and Pathways in Cervical Cancer: A Systematic Review and Integrated Bioinformatic Analysis

Affiliations
Review

Candidate Genes and Pathways in Cervical Cancer: A Systematic Review and Integrated Bioinformatic Analysis

Marjanu Hikmah Elias et al. Cancers (Basel). .

Abstract

Cervical cancer is the leading cause of cancer-related death among women in developing countries. However, no comprehensive molecular mechanism for cervical cancer has been established, as many studies were small-cohort studies conducted with small sample sizes. A thorough literature search was performed using the PubMed, Scopus, EBSCOhost, and Science Direct databases. Medical Subject Heading (MeSH) terms such as "Uterine Cervical Neoplasms" and "gene expression" were used as the keywords in all fields. A total of 4027 studies were retrieved, and only clinical studies, which used the microarray method to identify differentially expressed genes (DEGs) in the cervical tissue of cervical cancer patients, were selected. Following the screening, 6 studies were selected and 1128 DEGs were extracted from the data. Sixty-two differentially expressed genes from at least two studies were selected for further analysis by DAVID, STRING, and Cytoscape software. In cervical cancer pathogenesis, three significant clusters with high intermolecular interactions from the Protein-Protein Interaction (PPI) network complex revealed three major molecular mechanisms, including cell signaling, cell cycle, and cell differentiation. Subsequently, eight genes were chosen as the candidate genes based on their involvement in the relevant gene ontology (GO) and their interaction with other genes in the PPI network through undirected first neighbor nodes. The present systematic review improves our understanding of the molecular mechanism of cervical cancer and the proposed genes that can be used to expand the biomarker panel in the screening for cervical cancer. The targeted genes may be beneficial for the development of better treatment strategies.

Keywords: cervical cancer; differentially expressed gene; gene ontology; molecular pathway.

PubMed Disclaimer

Conflict of interest statement

The authors have no competing interests to declare that are relevant to the content of this article. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
PRISMA flow diagram for studies’ selection in this systematic review.
Figure 2
Figure 2
Venn diagram of the DEGs from all the selected studies.
Figure 3
Figure 3
PPI network of the DEGs collected from the selected studies.
Figure 4
Figure 4
Protein interaction through undirected first neighbor of the candidate genes (highlighted in yellow) from cluster 1: (a) CDKN2A, (b) VEGFA, (c) PTGS2, (d) MCM family, and (e) KRT family.

References

    1. Arbyn M., Weiderpass E., Bruni L. Estimates of incidence and mortality of cervical cancer in 2018: A worldwide analysis. Lancet Glob. Health. 2020;8:e191–e203. doi: 10.1016/S2214-109X(19)30482-6. - DOI - PMC - PubMed
    1. Fontham E.T.H., Wolf A.M.D., Church T.R., Etzioni R., Flowers C.R., Herzig A., Guerra C.E., Oeffinger K.C., Shih Y.-C.T., Walter L.C., et al. Cervical cancer screening for individuals at average risk: 2020 guideline update from the American Cancer Society. CA Cancer J. Clin. 2020;70:321–346. doi: 10.3322/caac.21628. - DOI - PubMed
    1. Abu-Rustum N.R., Yashar C.M., Bean S., Bradley K., Campos S.M., Chon H.S., Chu C., Cohn D., Crispens M.A., Damast S., et al. NCCN Guidelines Insights: Cervical Cancer, Version 1.2020: Featured Updates to the NCCN Guidelines. J. Natl. Compr. Cancer Netw. 2020;18:660–666. doi: 10.6004/jnccn.2020.0027. - DOI - PubMed
    1. US Preventive Services Task Force Screening for Cervical Cancer: US Preventive Services Task Force Recommendation Statement. JAMA. 2018;320:674–686. doi: 10.1001/jama.2018.10897. - DOI - PubMed
    1. Huang J., Qian Z., Gong Y., Wang Y., Guan Y., Han Y., Yi X., Huang W., Ji L., Xu J., et al. Comprehensive genomic variation profiling of cervical intraepithelial neoplasia and cervical cancer identifies potential targets for cervical cancer early warning. J. Med. Genet. 2019;56:186. doi: 10.1136/jmedgenet-2018-105745. - DOI - PMC - PubMed

LinkOut - more resources