LRG1 expression indicates unfavorable clinical outcome in hepatocellular carcinoma.

Chun-Hua Wang,Chris Zhiyi Zhang,Jing-Ping Yun,Min Li,Jia Fu,Ruo-Yao Zhou,Li-Li Liu

doi:10.18632/oncotarget.5967

Abstract

Leucine-rich-alpha-2-glycoprotein1 (LRG1) is a novel oncogene-associated protein which has been clarified vital to the progression of human cancers, but its role in hepatocellular carcinoma (HCC) remains unclear. Here, we showed that the expression of LRG1 was noticeably increased in HCC tissues, compared to the nontumorous tissues. High LRG1 expression was significantly associated with tumor size (P = 0.004), tumor differentiation (P = 0.010), TNM stage (P < 0.001) and vascular invasion (P = 0.019). Kaplan-Meier analysis showed that LRG1 expression was closely correlated to overall survival and disease-free survival in a training cohort of 474 patients with HCC. The correlation was further validated in an independent cohort of 303 HCC patients. The prognostic implication of LRG1 was confirmed by stratified survival analyses. Multivariate Cox regression model indicated LRG1 as an independent poor prognostic indicator for overall survival (Hazard ratio = 1.582, 95% confident interval: 1.345-1.862, P < 0.001) and disease-free survival (Hazard ratio = 1.280, 95% confident interval: 1.037-1.581, P = 0.022) in HCC. In vitro data showed that LRG1 markedly promoted cell migration but has no effect on cell proliferation. Collectively, our data show that LRG1 is markedly up-regulated and serves as an independent factor of poor outcomes in HCC. Our study therefore provides a promising biomarker for prognostic prediction in clinical management of HCC.

Highlights

Hepatocellular carcinoma (HCC) represents the fifth most common cancer, and is the third leading cause of cancer death worldwide [1]
Current literatures show that LRG1 is closely associated with cancer metastasis and poor prognosis, largely due to its effects on promoting cell invasion, angiogenesis, and migration
Zhong et al reported that LRG1 knockdown by RNA interference inhibited cell growth and promoted apoptosis in glioblastoma in vitro and in vivo [20]

Summary

Introduction

Hepatocellular carcinoma (HCC) represents the fifth most common cancer, and is the third leading cause of cancer death worldwide [1]. It is very helpful to identify risk factors and biomarkers for early diagnosis and prognostic prediction in patients with HCC. Leucine-richalpha-2-glycoprotein (LRG1), a membrane-associated LRR family member, has been predicted as a regulator of glucan synthesis [5], cell adhesion [6], and cell migration [7]. Increased LRG1 expression has been demonstrated in ovarian cancer [11], non-small cell lung cancer [12], gastric cancer [13], pancreatic cancer [14] and leukemia [15]. These data suggest a potential role of LRG1 in cancer progression

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Results

Conclusion