Glia Maturation Factor Beta as a Novel Biomarker and Therapeutic Target for Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) is one of the most common types of cancer. The novel sensitive biomarkers and therapeutic targets are urgently needed for the early diagnosis of HCC and improvement of clinical outcomes. Glia maturation factor-β (GMFB) is a growth and differentiation factor for both glia and neurons and has been found to be tightly involved in inflammation and neurodegeneration conditions. In our study, the expression level of GMFB was significantly up-regulated in patients with HCC and positively co-expression with tumor node metastases (TNM) stage and histopathological grade of HCC. The high expression level of GMFB was remarkably associated with poor overall survival, which mainly occurred in males rather than females. Multivariate analysis revealed GMFB to be an independent prognostic factor for overall survival in patients with HCC. Results of Gene Ontology (GO) and KEGG pathways analysis showed that down-regulation of pathways related to protein translation and mitochondria function were enriched. Protein-protein interaction analysis revealed the central role of mitochondria protein in HCC. The downregulation of genes involved in glycolysis and gluconeogenesis was observed among the co-expression genes of GMFB. Knockdown of GMFB in Hep3B significantly inhibited proliferation, migration, and invasion of Hep3B cells, and also downregulated the expression levels of some of metal matrix proteinase (MMP), increased mtDNA copy number and loss of mitochondrial transmembrane potential. GMFB influences the malignancy rate of HCC possibly through regulation of the expression of MMPs, mtDNA function and glycolysis. We proposed that GMFB was a promising HCC diagnostic and prognostic biomarker and therapeutic target in HCC.

Glia Maturation Factor β as a Novel Independent Prognostic Biomarker and Potential Therapeutic Target of Kidney Renal Clear Cell Carcinoma

“…OS analysis showed that Gmfb expression was negatively correlated with the hazard ratio (HR) of KIRC but positively correlated with the HR of LIHC in pan-cancers (Figure 1A). This was consistent with a previous report (24), in which Gmfb expression was negatively correlated with the HR of KIRC but positively correlated with the HR of adrenocortical carcinoma (ACC) (Figure 1A). Based on the correlation of Gmfb with OS and DFS in pan-cancer analysis, GMFB may be a promising novel prognostic factor for KIRC.…”

“…FP205-02, Tiangen Biotech, Beijing, China) were used for conducting qRT-PCR on a LightCycler 96 Detection System (Bio-Rad Laboratories, Hercules, CA, USA). Data were analyzed using the 2 −ΔΔCt method ( 24 ). Oligos were synthesized by Sangon Biotech.…”

“…Caki-2 cells were seeded in six-well plates and grown to 80%–90% confluence. Confluent cell monolayers were scratched using a sterile 200-µl pipette tip and rinsed with PBS to remove scratched cells according to our previous work ( 24 ). Wound closure was observed after 24 h. The wound closure rate was calculated as follows: wound closure (%) = (the area of initial wound − the area of the final wound)/area of initial wound × 100.…”

“…The migration and invasion abilities of cells were assessed using transwell migration (without Matrigel) and invasion (with Matrigel) assays in 24 wells according to our previous work ( 24 ). Cell suspensions in an FBS-free medium were added to the upper transwell chambers (24-well, 8-μm pores; BD, Franklin Lakes, NJ, USA), whereas 600 µl of the medium was supplemented with 10% FBS and added to the lower transwell chambers.…”

“…It has been shown that the upregulation of GMFB is closely related to neurodegenerative disorders such as Parkinson’s disease ( 23 ). Our previous work revealed that GMFB functions as a novel independent prognostic biomarker and therapeutic target for liver hepatocellular carcinoma (LIHC) ( 24 ). However, the role of GMFB in KIRC remains unclear.…”