GGT5 Is an Independent Prognostic Biomarker in Stomach Adenocarcinoma
Yong Huang, Hailang Zhou, Junwei Zou, Dong Wang
Abstract
Gastric cancer is one of the cancers with the highest incidence in the world. Gamma-glutamyltransferase 5 (GGT5) is expressed in different cancers and its role in cancers remains unclear. In this study, we aimed to evaluate the value of GGT5 in stomach adenocarcinoma (STAD). In TCGA, patients with high GGT5 expression had poor overall survival ( <a:math xmlns:a="http://www.w3.org/1998/Math/MathML" id="M1"> <a:mi>P</a:mi> <a:mo>=</a:mo> <a:mn>0.006</a:mn> </a:math> ). Based on GSE62254, high expression of GGT5 was associated with poor OS ( <c:math xmlns:c="http://www.w3.org/1998/Math/MathML" id="M2"> <c:mi>P</c:mi> <c:mo>=</c:mo> <c:mn>0.014</c:mn> </c:math> ) and PFS ( <e:math xmlns:e="http://www.w3.org/1998/Math/MathML" id="M3"> <e:mi>P</e:mi> <e:mo>=</e:mo> <e:mn>0.042</e:mn> </e:math> ). The same result was observed in GSE14210. We further discovered that GGT5 expression was associated with stage, grade, and T stage. Further prognostic analysis of GGT5 showed that GGT5 was associated with prognosis in both univariate analysis ( <g:math xmlns:g="http://www.w3.org/1998/Math/MathML" id="M4"> <g:mi>P</g:mi> <g:mo>=</g:mo> <g:mn>0.032</g:mn> </g:math> ) and multivariate analysis ( <i:math xmlns:i="http://www.w3.org/1998/Math/MathML" id="M5"> <i:mi>P</i:mi> <i:mo>=</i:mo> <i:mn>0.029</i:mn> </i:math> ). We used gene set enrichment analysis (GSEA) to explore the possible mechanism of GGT5. GSEA suggests that overexpression of GGT5 may be involved in leukocyte transendothelial migration, JAK-STAT signaling pathway, MAPK signaling pathway, and melanoma. The high-expression GGT5 group had higher concentrations of M2 macrophages, T cell regulators, and monocytes, but the contents of plasma cells and M1 macrophages were higher in the low-expression GGT5 group. The results showed that the ESTIMATEScore, ImmuneScore, and StromalScore of the high-expression GGT5 group were higher than those of the low-expression GGT5 group. PD1 and CTLA4 expression levels were higher in the high-expression GGT5 group. The high-expression GGT5 group may be more effective for immunotherapy. These results suggested that GGT5 could be a potential prognostic molecular predictor in STAD.