Abstract
GNAO1, the alpha O1 subunit of G protein, was reported to be significantly downregulated in hepatocellular carcinoma (HCC), as well as being implicated in a variety of intracellular biological events; findings suggest that it may act as a tumor suppressor. Our goal was to further explore the expression of GNAO1 in HCC patients and its potential clinical significance. Oncomine and Kaplan–Meier plotter databases were used to assess the mRNA expression of GNAO1 in HCC tissues and patient survival time. Subsequently, immunohistochemistry (IHC) was used to measure GNAO1 protein level in tissue from 79 cases of HCC and paired adjacent tissues. The Kaplan–Meier survival analysis, Cox regression model, and prognostic nomogram were used to evaluate the prognostic role of GNAO1 in HCC. Results demonstrated that mRNA and protein expressions of GNAO1 were both lower in HCC tissues than in adjacent tissues (all p < 0.01). HCC patients with high expression of GNAO1 had better relapse-free survival (RFS) than those with low GNAO1 expression (all p < 0.05). A high expression of GNAO1, meanwhile, functioned as a good predictor of late relapse for HCC (p < 0.05). The nomogram consisting of GNAO1 expression and the tumor-node-metastasis (TNM) model presented good ability in predicting the 3-year relapse for HCC (C-index = 0.614). In conclusion, GNAO1 was a reliable biomarker of relapse prediction for HCC.
Highlights
Liver cancer is one of the most lethal and prevalent cancers worldwide and has recently become the third leading cause of cancer-related mortality in humans [1]
Oncomine Database Analysis. e differential expression of GNAO1 mRNA between Hepatocellular carcinoma (HCC) and normal liver tissues was reviewed in the Oncomine database, which is a cancer microarray database and web-based data-mining platform aimed at facilitating discovery from genome-wide expression analysis [17]. e threshold settings were as follows: gene ranking of top 10%, a fold change of 2.0, and a p value of 1E-4
Low mRNA and Protein Levels of GNAO1 in HCC Tissues. ere were 5 RNA chips with a total of 413 HCC and 340 normal liver tissues involved in the analysis of differential expression of GNAO1 mRNA in the Oncomine database
Summary
Liver cancer is one of the most lethal and prevalent cancers worldwide and has recently become the third leading cause of cancer-related mortality in humans [1]. Established major risk factors for HCC include chronic infection with hepatitis B virus (HBV) and hepatitis C virus, excess alcohol consumption, and nonalcoholic fatty liver disease. Despite of recent progress in diagnosis and treatment, the clinical outcomes of HCC patients remain very poor. Us, it is crucial to explore a novel biomarker of early diagnosis or prognostication for HCC. GNAO1 encodes the alpha O1 subunit of guanine nucleotide-binding proteins, which can trigger signaling cascades and regulate several cellular events when they bind to a serpentine receptor [3].
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