Lrig1 is a positive prognostic marker in hepatocellular carcinoma

OncoTargets and Therapy, Nov 2016

Lrig1 is a positive prognostic marker in hepatocellular carcinoma Bo Yang,1,2 Chen Dai,1,2 Rumeng Tan,1,2 Bo Zhang,1,2 Xiao Meng,3 Jing Ye,3 Xinqiang Wang,1,2 Lai Wei,1,2 Fan He,4 Zhishui Chen1,2 1Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 2Key Laboratory of Ministry of Health and Key Laboratory of Ministry of Education, Wuhan, Hubei, People’s Republic of China; 3Department of Pathology, Liaocheng People’s Hospital, Liaocheng, Shandong, People’s Republic of China; 4Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China Background: The prevalence of hepatocellular carcinoma (HCC) is increasing worldwide. As a consequence, there is an urgent need for identifying molecular markers of HCC development and progression. Recently, several studies have suggested that the Lrig1 may have prognostic implications in various cancer types, but its clinical value in HCC is not well evaluated. Materials and methods: In this study, the expression level of Lrig1 was examined in 133 HCC tissues and adjacent normal tissues by immunohistochemistry. Furthermore, potential associations between Lrig1 expression and the carcinoma clinical parameters were investigated, including recurrence and survival rate. We silenced the Lrig1 in the normal liver cell line (LO2) and liver cancer cell line (Hep-G2) in vitro by the small interference RNA and detected its influence on proliferation, migration, and invasion. Results: The expression of Lrig1 was significantly downregulated in liver cancer tissues and cell lines, and its expression levels were related to tumor size, tumor–node–metastasis staging and tumor recurrence. Furthermore, analysis of 6-year survival of 133 HCC patients showed that those with stronger Lrig1 expression had significantly longer overall survival time than those with weaker Lrig1 expression. In addition, decreased expression of Lrig1 in vitro promoted the growth, migration, or invasion of normal liver cells and cancer cells. Conclusion: Our findings demonstrate that Lrig1 could serve as a potential marker in the prognosis of patients with HCC. We also revealed that Lrig1 might be involved in the metastatic progression of liver cancer. However, its clinical value should be further investigated in the future. Keywords: Lrig1, hepatocellular carcinoma, prognosis, immunohistochemistry, siRNA, invasion, migration

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Lrig1 is a positive prognostic marker in hepatocellular carcinoma

OncoTargets and Therapy lrig1 is a positive prognostic marker in hepatocellular carcinoma Bo Zhang 1 2 4 Xiao Meng 0 4 Jing Ye 0 4 Xinqiang Wang 1 2 4 0 Department of Pathology, l iaocheng People's hospital , liaocheng, shandong, People's republic of china 1 Key laboratory of Ministry of health and Key laboratory of Ministry of education , Wuhan, hubei, People's republic of china 2 institute of Organ Transplantation, Tongji h ospital, Tongji Medical c ollege, h uazhong University of science and Technology , Wuhan, hubei, People's republic of china 3 Department of n ephrology, Tongji hospital, Tongji Medical college, h uazhong University of s cience and Technology , Wuhan, hubei, People's republic of china 4 Zhishui chen PowerdbyTCPDF(ww.tcpdf.org) Fan he 4 Background: The prevalence of hepatocellular carcinoma (HCC) is increasing worldwide. As a consequence, there is an urgent need for identifying molecular markers of HCC development and progression. Recently, several studies have suggested that the Lrig1 may have prognostic implications in various cancer types, but its clinical value in HCC is not well evaluated. Materials and methods: In this study, the expression level of Lrig1 was examined in 133 HCC tissues and adjacent normal tissues by immunohistochemistry. Furthermore, potential associations between Lrig1 expression and the carcinoma clinical parameters were investigated, including recurrence and survival rate. We silenced the Lrig1 in the normal liver cell line (LO2) and liver cancer cell line (Hep-G2) in vitro by the small interference RNA and detected its influence on proliferation, migration, and invasion. Results: The expression of Lrig1 was significantly downregulated in liver cancer tissues and cell lines, and its expression levels were related to tumor size, tumor-node-metastasis staging and tumor recurrence. Furthermore, analysis of 6-year survival of 133 HCC patients showed that those with stronger Lrig1 expression had significantly longer overall survival time than those with weaker Lrig1 expression. In addition, decreased expression of Lrig1 in vitro promoted the growth, migration, or invasion of normal liver cells and cancer cells. Conclusion: Our findings demonstrate that Lrig1 could serve as a potential marker in the prognosis of patients with HCC. We also revealed that Lrig1 might be involved in the metastatic progression of liver cancer. However, its clinical value should be further investigated in Lrig1; hepatocellular carcinoma; prognosis; immunohistochemistry; siRNA - open access to scientific and medical research O r i g i n a l r e s e a r c h Introduction Hepatocellular carcinoma (HCC), a major pathological type of primary liver cancer, is one of the serious threats to human health and the third leading cause of cancerrelated deaths worldwide.1,2 The highest incidence rate of HCC has been reported in the developing world and is steadily increasing across the developed world.3 Currently, surgical operation is the most effective treatment of HCC. However, after hepatic resection and liver transplantation, the recurrence incidence and prognosis are still not optimistic. Totally 65%–80% of the cases recur after surgical therapy, and the crucial postoperative 5-year survival rate ranges from 30% to 40%.4,5 The late diagnosis for this rapidly progressing tumor still remains an obstacle in the improvement of prognosis for HCC patients. Therefore, identifying an effective biomarker for early diagnosis and improving treatment strategies are required. The leucine-rich repeats and immunoglobulin-like domains (Lrig) family comprises three paralogous genes, termed Lrig1, Lrig2, and Lrig3, which are widely expressed in human 8 1 0 2 l u J 2 1 n o 7 0 2 . 6 4 . 9 5 . 7 3 y b / m o c . s s re . and mouse tissues. Moreover, Lrig1 is a transmembrane protein that is involved in the regulation of cellular signal transduction, whose transcript is located at chromosome 3p14.3, a region frequently deleted in various types of human cancers.6 In the last decade, Lrig1 has been hypothesized to function as a tumor suppressor in vivo and in vitro. Recently, experimental and clinical data have subsequently supported this hypothesis. Numerous previous reports have shown that Lrig1 is downregulated in several types of tumors, such as cutaneous squamous cell carcinoma, renal cell carcinoma, glioblastoma, and breast cancer.7–10 Recently, researchers revealed that the mechanism of Lrig1 may involve the inhibition of the PI3K/Akt and Ras/Raf/ERK signal transduction pathways.11 However, the expression of Lrig1 and its clinical significance in HCC remain unclear. In addition, Yokdang et al12 found that Lrig1 may represent a barrier to epithelialto-mesenchymal transition (EMT). Depletion of endogenous Lrig1 in human mammary epithelial cells expands the stem cell population, augments mammosphere formation, and acceler.vdoep lsyeon actaenscEerM.LTo.wLerirge1xipsrfersesqiounenotlfyitmsemthRyNlaAtedanind hpuro (...truncated)


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Bo Yang, Chen Dai, Rumeng Tan, Bo Zhang, Xiao Meng, Jing Ye, Xinqiang Wang, Lai Wei, Fan He, Zhishui Chen. Lrig1 is a positive prognostic marker in hepatocellular carcinoma, OncoTargets and Therapy, 2016, pp. 7071-7079, DOI: 10.2147/OTT.S112534