Biological and clinical significance of the glypican-3 gene in human lung adenocarcinoma: An in silico analysis.
Raihan Rahman ImonSharmin AktarNiaz MorshedSuza Mohammad NurRumana MahtarinFarazi Abinash RahmanMd Enamul Kabir TalukderRahat AlamTomasz M KarpińskiFoysal AhammadMazin A ZamzamiShing Cheng TanPublished in: Medicine (2023)
Glypican-3 (GPC3), a membrane-bound heparan sulfate proteoglycan, has long been found to be dysregulated in human lung adenocarcinomas (LUADs). Nevertheless, the function, mutational profile, epigenetic regulation, co-expression profile, and clinicopathological significance of the GPC3 gene in LUAD progression are not well understood. In this study, we analyzed cancer microarray datasets from publicly available databases using bioinformatics tools to elucidate the above parameters. We observed significant downregulation of GPC3 in LUAD tissues compared to their normal counterparts, and this downregulation was associated with shorter overall survival (OS) and relapse-free survival (RFS). Nevertheless, no significant differences in the methylation pattern of GPC3 were observed between LUAD and normal tissues, although lower promoter methylation was observed in male patients. GPC3 expression was also found to correlate significantly with infiltration of B cells, CD8+, CD4+, macrophages, neutrophils, and dendritic cells in LUAD. In addition, a total of 11 missense mutations were identified in LUAD patients, and ~1.4% to 2.2% of LUAD patients had copy number amplifications in GPC3. Seventeen genes, mainly involved in dopamine receptor-mediated signaling pathways, were frequently co-expressed with GPC3. We also found 11 TFs and 7 miRNAs interacting with GPC3 and contributing to disease progression. Finally, we identified 3 potential inhibitors of GPC3 in human LUAD, namely heparitin, gemcitabine and arbutin. In conclusion, GPC3 may play an important role in the development of LUAD and could serve as a promising biomarker in LUAD.
Keyphrases
- end stage renal disease
- copy number
- genome wide
- chronic kidney disease
- ejection fraction
- dendritic cells
- newly diagnosed
- free survival
- peritoneal dialysis
- endothelial cells
- gene expression
- dna methylation
- cell proliferation
- poor prognosis
- immune response
- squamous cell carcinoma
- radiation therapy
- metabolic syndrome
- regulatory t cells
- autism spectrum disorder
- deep learning
- machine learning
- young adults
- induced pluripotent stem cells
- artificial intelligence
- transcription factor
- papillary thyroid
- long non coding rna
- human health
- big data
- rna seq
- bioinformatics analysis
- induced apoptosis