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

ABSTRACT: 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.

SUBMITTER: Zhang L

PROVIDER: S-EPMC8716600 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Currently, the occurrence and mortality rate of cervical cancer is high, particularly in low-to-middle-income countries. Therefore, the development of novel diagnostic and treatment strategies for cervical cancer is urgently required. The aim of the present study was to assess the prognostic significance of fibronectin type III domain containing 3B (FNDC3B) expression in patients with cervical cancer and to determine the underlying mechanism of FNDC3 in tumor development. Analysis of the ONCOMINE database revealed that FNDC3B was significantly upregulated in cervical cancer tissue compared with normal tissue. Additionally, FNDC3B expression data and the clinical characteristics of patients with cervical cancer were obtained from the cBioPortal database. Correlations between FNDC3B expression and overall survival were subsequently investigated. The results revealed that increased FNDC3B expression was significantly correlated with a lower overall survival in patients with cervical cancer. A co-expression network was subsequently constructed to elucidate the function of FNDC3B in cervical cancer. Co-expression genes for FNDC3B were obtained from the cBioPortal database and were subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. The results demonstrated that the genes were enriched in pathways associated with migration, invasion, endoplasmic reticulum (ER) stress and the unfolded protein response (UPR). Furthermore, immunofluorescence results obtained from the Human Protein Atlas revealed that the FNDC3B protein was localized to the ER. The results revealed that upregulated FNDC3B expression may be a biomarker for poor prognosis for patients with cervical cancer. Additionally, the results revealed that FNDC3B may serve an oncogenic role in cancer development via ER stress, UPR, cell migration and invasion. However, further studies are required to determine the exact molecular mechanism of FNDC3B in the development of cervical cancer and to assess its potential as a novel therapeutic target for the treatment of this disease.

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

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