Loss of alanine-glyoxylate and serine-pyruvate aminotransferase expression accelerated the progression of hepatocellular carcinoma and predicted poor prognosis

Shiqi Shen,Juling Ji,Wenchao Li,Yi Shen,Yufeng Sun,Xuejing Yang,Peng Lu,Xiaojing Zhang,Bing Lu

doi:10.1186/s12967-019-02138-5

Abstract

BackgroundAccumulated studies reported abnormal gene expression profiles of hepatocellular carcinoma (HCC) by cDNA microarray. We tried to merge cDNA microarray data from different studies to search for stably changed genes, and to find out better diagnostic and prognostic markers for HCC.MethodsA systematic review was performed by searching publications indexed in Pubmed from March 1, 2001 to July 1, 2016. Studies that reporting cDNA microarray profiles in HCC, containing both tumor and nontumor data and published in English-language were retrieved. The differentially expressed genes from eligible studies were summarized and ranked according to the frequency. High frequency genes were subjected to survival analyses. The expression and prognostic value of alanine-glyoxylate and serine-pyruvate aminotransferase (AGXT) was further evaluated in HCC datasets in Oncomine and an independent HCC tissue array cohort. The role of AGXT in HCC progression was evaluated by proliferation and migration assays in a human HCC cell line.ResultsA total of 43 eligible studies that containing 1917 HCC patients were included, a list of 2022 non redundant abnormally expressed genes in HCC were extracted. The frequencies of reported genes were ranked. We finally obtained a list of only five genes (AGXT; ALDOB; CYP2E1; IGFBP3; TOP2A) that were differentially expressed in tumor and nontumor tissues across studies and were significantly correlated to HCC prognosis. Only AGXT had not been reported in HCC. Reduced expression of AGXT reflected poor differentiation of HCC and predicts poor survival. Knocking down of AGXT enhanced cell proliferation and migration of HCC cell line.ConclusionsThe present study supported the feasibility and necessity of systematic review on discovering new and reliable biomarkers for HCC. We also identified a list of high frequency prognostic genes and emphasized a critical role of AGXT deletion during HCC progression.

Highlights

Accumulated studies reported abnormal gene expression profiles of hepatocellular carcinoma (HCC) by cDNA microarray
We performed a systematic review of studies that reported cDNA microarray data for both tumor and nontumor liver tissues of HCC patients and came up with a list of five genes that were differentially expressed in tumor and nontumor tissues across different studies and were significantly correlated to HCC prognosis
The full text of these remaining 99 studies was retrieved and further assessed for eligibility. Of these 99 publications, 56 were excluded

Summary

Introduction

Accumulated studies reported abnormal gene expression profiles of hepatocellular carcinoma (HCC) by cDNA microarray. We tried to merge cDNA microarray data from different studies to search for stably changed genes, and to find out better diagnostic and prognostic markers for HCC. Hepatocellular carcinoma (HCC) accounts for 70–85% of the total liver cancer burden. The accurate diagnosis and proper treatment of HCC is challenging. Options for HCC treatment remain limited, surgical resection is considered the only “curative treatment”. HCC patients do not have overt symptoms in the early stages, 80% of patients have widespread HCC at the time of diagnosis and are not candidates for surgical treatment. The 5-year survival rate is poor (about 38%) [2]

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Conclusion