AUTHOR=Zhang Luhan , Yu Hong , Deng Tian , Ling Li , Wen Juan , Lv Mingfen , Ou Rongying , Wang Qiaozhi , Xu Yunsheng 

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

JOURNAL=Frontiers in Oncology

VOLUME=Volume 11 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.783868

DOI=10.3389/fonc.2021.783868

ISSN=2234-943X

ABSTRACT=Human papillomavirus (HPV)-triggered cervical carcinogenesis is a multistep process spanning persistent infection, precancerous lesions, and cervical cancer (CCa). Although molecular alterations driven by viral oncoproteins are necessary to cervical carcinogenesis, the key regulators behind the multistep process remain not well-understood. It is pivotal to identify the key genes involved in cervical carcinogenesis for ameliorating early diagnosis and therapy of the disease. Here we re-analyzed mRNA expression profiles in cervical samples spanning 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. Furthermore, the differentially expressed genes (DEGs) that could distinguish all stages in stepwise progression of CCa were screened out. And then the key genes involved in HPV-CCa were identified. As a result, the genes involved in DNA replication/repair and cell cycle was up-regulated 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 in stepwise progression of CCa. 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). Receiver operating characteristic (ROC) analysis of CIN and CCa showed that FNDC3B had the highest sensitivity and specificity for CCa. Taken together, the current data showed that FNDC3B and BPGM were key genes involved in HPV-mediated transformation from normalcy to precancerous lesions and CCa.