LRG1 expression indicates unfavorable clinical outcome in hepatocellular carcinoma

// Chun-Hua Wang 1, 2, * , Min Li 1, 2, * , Li-Li Liu 1, 2 , Ruo-Yao Zhou 3 , Jia Fu 1, 2 , Chris Zhiyi Zhang 1, 2 , Jing-Ping Yun 1, 2 1 Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China 2 Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China 3 Okemos High School, Okemos MI 48864, USA * These authors have contributed equally to this work Correspondence to: Jing-Ping Yun, e-mail: yunjp@sysucc.org.cn Keywords: LRG1, prognosis, immunohistochemistry, hepatocellular carcinoma Received: March 27, 2015      Accepted: October 09, 2015      Published: October 19, 2015 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.