Cargando…

FNDC3B and BPGM Are Involved in Human Papillomavirus-Mediated Carcinogenesis of Cervical Cancer

Human papillomavirus (HPV)-mediated cervical carcinogenesis is a multistep progressing from persistent infection, precancerous lesion to cervical cancer (CCa). Although molecular alterations driven by viral oncoproteins are necessary in cervical carcinogenesis, the key regulators behind the multiste...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Luhan, Yu, Hong, Deng, Tian, Ling, Li, Wen, Juan, Lv, Mingfen, Ou, Rongying, Wang, Qiaozhi, Xu, Yunsheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8716600/
https://www.ncbi.nlm.nih.gov/pubmed/34976823
http://dx.doi.org/10.3389/fonc.2021.783868
_version_ 1784624357921783808
author Zhang, Luhan
Yu, Hong
Deng, Tian
Ling, Li
Wen, Juan
Lv, Mingfen
Ou, Rongying
Wang, Qiaozhi
Xu, Yunsheng
author_facet Zhang, Luhan
Yu, Hong
Deng, Tian
Ling, Li
Wen, Juan
Lv, Mingfen
Ou, Rongying
Wang, Qiaozhi
Xu, Yunsheng
author_sort Zhang, Luhan
collection PubMed
description Human papillomavirus (HPV)-mediated cervical carcinogenesis is a multistep progressing from persistent infection, precancerous lesion to cervical cancer (CCa). Although molecular alterations driven by viral oncoproteins are necessary in cervical carcinogenesis, the key regulators behind the multistep process remain not well understood. It is pivotal to identify the key genes involved in the process for early diagnosis and treatment of this disease. Here we analyzed the mRNA expression profiles in cervical samples including normal, cervical intraepithelial neoplasia (CIN), and CCa. A co-expression network was constructed using weighted gene co-expression network analysis (WGCNA) to reveal the crucial modules in the dynamic process from HPV infection to CCa development. Furthermore, the differentially expressed genes (DEGs) that could distinguish all stages of progression of CCa were screened. The key genes involved in HPV-CCa were identified. It was found that the genes involved in DNA replication/repair and cell cycle were upregulated in CIN compared with normal control, and sustained in CCa, accompanied by substantial metabolic shifts. We found that upregulated fibronectin type III domain-containing 3B (FNDC3B) and downregulated bisphosphoglycerate mutase (BPGM) could differentiate all stages of CCa progression. In patients with CCa, a higher expression of FNDC3B or lower expression of BPGM was closely correlated with a shorter overall survival (OS) and disease-free survival (DFS). A receiver operating characteristic (ROC) analysis of CIN and CCa showed that FNDC3B had the highest sensitivity and specificity for predicting CCa development. Taken together, the current data showed that FNDC3B and BPGM were key genes involved in HPV-mediated transformation from normal epithelium to precancerous lesions and CCa.
format Online
Article
Text
id pubmed-8716600
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-87166002021-12-31 FNDC3B and BPGM Are Involved in Human Papillomavirus-Mediated Carcinogenesis of Cervical Cancer Zhang, Luhan Yu, Hong Deng, Tian Ling, Li Wen, Juan Lv, Mingfen Ou, Rongying Wang, Qiaozhi Xu, Yunsheng Front Oncol Oncology Human papillomavirus (HPV)-mediated cervical carcinogenesis is a multistep progressing from persistent infection, precancerous lesion to cervical cancer (CCa). Although molecular alterations driven by viral oncoproteins are necessary in cervical carcinogenesis, the key regulators behind the multistep process remain not well understood. It is pivotal to identify the key genes involved in the process for early diagnosis and treatment of this disease. Here we analyzed the mRNA expression profiles in cervical samples including normal, cervical intraepithelial neoplasia (CIN), and CCa. A co-expression network was constructed using weighted gene co-expression network analysis (WGCNA) to reveal the crucial modules in the dynamic process from HPV infection to CCa development. Furthermore, the differentially expressed genes (DEGs) that could distinguish all stages of progression of CCa were screened. The key genes involved in HPV-CCa were identified. It was found that the genes involved in DNA replication/repair and cell cycle were upregulated in CIN compared with normal control, and sustained in CCa, accompanied by substantial metabolic shifts. We found that upregulated fibronectin type III domain-containing 3B (FNDC3B) and downregulated bisphosphoglycerate mutase (BPGM) could differentiate all stages of CCa progression. In patients with CCa, a higher expression of FNDC3B or lower expression of BPGM was closely correlated with a shorter overall survival (OS) and disease-free survival (DFS). A receiver operating characteristic (ROC) analysis of CIN and CCa showed that FNDC3B had the highest sensitivity and specificity for predicting CCa development. Taken together, the current data showed that FNDC3B and BPGM were key genes involved in HPV-mediated transformation from normal epithelium to precancerous lesions and CCa. Frontiers Media S.A. 2021-12-16 /pmc/articles/PMC8716600/ /pubmed/34976823 http://dx.doi.org/10.3389/fonc.2021.783868 Text en Copyright © 2021 Zhang, Yu, Deng, Ling, Wen, Lv, Ou, Wang and Xu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Zhang, Luhan
Yu, Hong
Deng, Tian
Ling, Li
Wen, Juan
Lv, Mingfen
Ou, Rongying
Wang, Qiaozhi
Xu, Yunsheng
FNDC3B and BPGM Are Involved in Human Papillomavirus-Mediated Carcinogenesis of Cervical Cancer
title FNDC3B and BPGM Are Involved in Human Papillomavirus-Mediated Carcinogenesis of Cervical Cancer
title_full FNDC3B and BPGM Are Involved in Human Papillomavirus-Mediated Carcinogenesis of Cervical Cancer
title_fullStr FNDC3B and BPGM Are Involved in Human Papillomavirus-Mediated Carcinogenesis of Cervical Cancer
title_full_unstemmed FNDC3B and BPGM Are Involved in Human Papillomavirus-Mediated Carcinogenesis of Cervical Cancer
title_short FNDC3B and BPGM Are Involved in Human Papillomavirus-Mediated Carcinogenesis of Cervical Cancer
title_sort fndc3b and bpgm are involved in human papillomavirus-mediated carcinogenesis of cervical cancer
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8716600/
https://www.ncbi.nlm.nih.gov/pubmed/34976823
http://dx.doi.org/10.3389/fonc.2021.783868
work_keys_str_mv AT zhangluhan fndc3bandbpgmareinvolvedinhumanpapillomavirusmediatedcarcinogenesisofcervicalcancer
AT yuhong fndc3bandbpgmareinvolvedinhumanpapillomavirusmediatedcarcinogenesisofcervicalcancer
AT dengtian fndc3bandbpgmareinvolvedinhumanpapillomavirusmediatedcarcinogenesisofcervicalcancer
AT lingli fndc3bandbpgmareinvolvedinhumanpapillomavirusmediatedcarcinogenesisofcervicalcancer
AT wenjuan fndc3bandbpgmareinvolvedinhumanpapillomavirusmediatedcarcinogenesisofcervicalcancer
AT lvmingfen fndc3bandbpgmareinvolvedinhumanpapillomavirusmediatedcarcinogenesisofcervicalcancer
AT ourongying fndc3bandbpgmareinvolvedinhumanpapillomavirusmediatedcarcinogenesisofcervicalcancer
AT wangqiaozhi fndc3bandbpgmareinvolvedinhumanpapillomavirusmediatedcarcinogenesisofcervicalcancer
AT xuyunsheng fndc3bandbpgmareinvolvedinhumanpapillomavirusmediatedcarcinogenesisofcervicalcancer