scholarly journals Expression Status and Prognostic Significance of Gamma-Glutamyl Transpeptidase Family Genes in Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Shan Tian ◽  
Jiao Li ◽  
Yingyun Guo ◽  
Weiguo Dong ◽  
Xin Zheng
Keyword(s):  
Hepatocellular Carcinoma ◽  
Dna Methylation ◽  
Prognostic Value ◽  
Expression Patterns ◽  
Prognostic Significance ◽  
Gamma Glutamyl Transpeptidase ◽  
Gamma Glutamyl ◽  
Spearman Coefficient ◽  
Glutamyl Transpeptidase ◽  
Curative Hepatectomy

PurposeGamma-glutamyl transpeptidase (GGT) family genes play crucial roles in the formation and progression of several solid tumors. However, the expression patterns and the prognostic significance of GGT members in hepatocellular carcinoma (HCC) remain unknown. This study was designed to determine the expression profiles of GGT family members in HCC and validate the prognostic value of serum GGT protein in patients with HCC.MethodWe comprehensively searched public resources based on the LIHC dataset to determine the expression patterns, prognostic significance, DNA methylation status, immune infiltration, and biological pathways of GGT family genes in HCC. Subsequently, we validated the prognostic value of serum GGT protein in 85 patients with early-stage HCC subjected to curative hepatectomy from the Renmin Hospital of Wuhan University.ResultsExcept for GGT1, other GGT family members (GGT5, GGT6, and GGT7) were found to be differentially expressed in primary HCC samples (N = 371) and normal control tissues (N = 50). Furthermore, a positive relationship was not only observed between GGT1 and GGT5 (Spearman coefficient: 0.24, P = 5.143 × 10−6) but also between GGT5 and GGT6 (Spearman coefficient: 0.38, P = 1.24 × 10−13). The expression of GGT1, GGT5, and GGT7 was correlated with overall survival (OS), and GGT7 was associated with disease-free survival (DFS) in patients with HCC. Negative associations between DNA methylation and expression of mRNA were observed for GGT1 (Spearman coefficient: −0.38, P = 6.24e-14), GGT6 (Spearman coefficient: −0.29, P = 1.23e-8), and GGT7 (Spearman coefficient: −0.34, P=6.7e-11). GGT family genes were well correlated with the infiltration levels of immune cells in HCC, especially CD4+ T cells, macrophages, and dendritic cells. Finally, when validated with clinical data from the Renmin cohort, a high expression of serum GGT protein was identified as a strong prognostic element of unfavorable OS (HR = 3.114, P = 0.025), but not of DFS (HR = 1.198, P = 0.05) in patients with HCC subjected to curative hepatectomy.ConclusionTo our knowledge, this is the first comprehensive analysis of the expression patterns and clinical value of GGT family genes in patients with HCC. Our study laid the foundation for the clinical application of the GGT protein in the survival assessment of patients with HCC.

scholarly journals Predictive value of gamma-glutamyl transpeptidase to lymphocyte count ratio in hepatocellular carcinoma patients with microvascular invasion

2020 ◽  
Author(s):  
Hongxing Zhang ◽  
Yu Zhou ◽  
Yicheng Li ◽  
Wanying Qin ◽  
Yunhua Zi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Risk Factor ◽  
Roc Curve ◽  
Lymphocyte Count ◽  
Poor Prognosis ◽  
Microvascular Invasion ◽  
Gamma Glutamyl Transpeptidase ◽  
Gamma Glutamyl ◽  
Count Ratio ◽  
Glutamyl Transpeptidase

Abstract Background: Microvascular invasion (MVI) is an independent risk factor for poor prognosis in hepatocellular carcinoma (HCC). However, there is still a lack of preoperative markers to predict MVI in HCC. This study intends to explore the potential application value of the gamma-glutamyl transpeptidase (GGT) to lymphocyte count ratio (GLR) in predicting MVI in HCC and provide guidance for clinical diagnosis and treatment. Methods: From March 2010 to December 2015, 230 HCC patients who underwent surgical treatment in the Affiliated Hospital of Guilin Medical University were selected. Clinicopathological parameters between the MVI group (n = 115) and the non-MVI group (n = 115) were comparatively analyzed. The GLR was used as the potential risk factor for HCC with MVI, and its optimal cut-off value was estimated by using the receiver operating characteristic (ROC) curve. The Kaplan-Meier method was used to analyze the survival of HCC patients, and univariate and multivariate Cox regression analyses were used to establish independent predictors affecting postoperative HCC patients. Results: The GLR levels in the MVI group and non-MVI group were 84.83 ± 61.84 and 38.42 ± 33.52 (p < 0.001), respectively. According to ROC curve analysis, the optimal cut-off value of GLR was 56.0, and the area under the ROC curve (AUC) was 0.781 (95% CI, 0.719-0.833) for the risk prediction of MVI in HCC patients. Multivariate analysis showed that tumor size > 5 cm, HCC combined with MVI and GLR > 56.0 were independent risk factors for poor prognosis in HCC patients. In addition, compared with the non-MVI group, patients in the MVI group had shorter progression-free survival (PFS) and overall survival (OS). Conclusion: GLR could be a predictive biomarker of HCC after operation and a potential predictor of HCC combined with MVI. Keywords: Hepatocellular carcinoma, Microvascular invasion, GLR, Predictive

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