Biomedical and Biotechnology Research Journal (Jan 2023)

Identification of hub genes in the fructose-1, 6 bisphosphate 1-protein interaction network based on differential expression, and survival impact on hepatocellular carcinoma patients

  • Bhavya Dawath,
  • Harshal Patole,
  • Norine Dsouza,
  • Kripa Purohit,
  • Shiney Peter

DOI
https://doi.org/10.4103/bbrj.bbrj_50_23
Journal volume & issue
Vol. 7, no. 2
pp. 238 – 246

Abstract

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Background: Hepatocytes, the cells of origin in hepatocellular carcinoma (HCC), accompany several altered metabolic pathways leading to adaptive metabolic switch and uncontrolled cell proliferation. Fructose-1, 6 bisphosphate 1 (FBP1) participates in gluconeogenesis and is reported as a potential tumor suppressor in several cancers. Our study aimed to conduct a network analysis to identify crucial hub genes interacting with FBP1 and possibly altered biological pathways based on the differential expression patterns of FBP1 in HCC patients. Methods: The expression analysis of FBP1 and its interactors was based on datasets retrieved from gene expression omnibus (GEO). The survival impact of differentially expressed genes was carried out using The Cancer Genome Atlas Dataset (TCGA) and performed in R studio. The FBP1 interaction network was visualized in Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and Cytoscape software. The Gene Ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis of FBP1 interactors was performed using Database for Annotation, Visualization, and Integrated Discovery (DAVID) and the hub genes were identified using the cytoHubba plugin in the Cytoscape software. Results: The analysis of the FBP1 interaction network revealed glucose-6-phosphate dehydrogenase (G6PD), aldolase, fructose-bisphosphate B (ALDOB), phosphoenolpyruvate carboxykinase 2 (PCK2), phosphoglucomutase 1 (PGM1) as crucial hub genes associated with HCC. The survival analysis of the hub genes showed the association of G6PD overexpression and ALDOB, PCK2, PGM1 underexpression with unfavorable overall survival. It also reveals the role of FBP1 network genes in metabolic and signaling pathways crucial for cell survival. Conclusions: The FBP1 hub genes might serve as promising therapeutic leads targeted toward the adaptive metabolic switch and uncontrolled cell proliferation in preventing HCC progression.

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