RESEARCH ARTICLE
Axl Expression Stratifies Patients with Poor Prognosis after Hepatectomy for Hepatocellular Carcinoma Jian Liu1☯, Kui Wang1☯, Zhenlin Yan1☯, Yong Xia1, Jun Li1, Lehua Shi1, Qifei Zou1, Xuying Wan2, Binghua Jiao3, Hongyang Wang4, Mengchao Wu1,4, Yongjie Zhang5*, Feng Shen1*
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1 Department of Hepatic Surgery, the Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China, 2 Department of Clinical Database, the Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China, 3 Department of Biochemistry and Molecular Biology, Second Military Medical University, Shanghai, China, 4 National Scientific Center for Liver Cancer, Shanghai, China, 5 Department of Biliary Surgery, the Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China ☯ These authors contributed equally to this work. * [email protected] (FS); [email protected] (YZ)
OPEN ACCESS Citation: Liu J, Wang K, Yan Z, Xia Y, Li J, Shi L, et al. (2016) Axl Expression Stratifies Patients with Poor Prognosis after Hepatectomy for Hepatocellular Carcinoma. PLoS ONE 11(5): e0154767. doi:10.1371/journal.pone.0154767 Editor: William B. Coleman, University of North Carolina School of Medicine, UNITED STATES
Abstract Background Axl is a receptor tyrosine kinase which plays an important role in multiple human malignancies.
Received: January 10, 2015 Accepted: April 19, 2016
Design
Published: May 16, 2016
The Axl expression was examined in several hepatocellular carcinoma(HCC) cell lines, paired tumor and nontumorous samples. Then, we examined cell growth curve, cell apoptosis and cell migration in SMMC-7721 cells over-expressed with Axl or siRNA against Axl, respectively. Finally, the prognostic value of Axl was investigated in a prospective cohort of 246 consecutive HCC patients undergoing curative hepatoectomy.
Copyright: © 2016 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: This work was supported by grants from National Natural Science Foundation of China (grant number 81071867 to KW; grant number 30772141 to SF; grant number 30921006 to HYW); a grant from the State Key Project on Infectious Diseases of China (grant number 2012ZX10002 -011,016 to FS); and a grant of Shanghai Hospital Development Program (grant number SHDC12010121 to FS). Competing Interests: The authors have declared that no competing interests exist.
Results We found Axl was positive in 22% of examined tumor tissues and all four cell lines. Overexpressing Axl in SMMC-7721 cells accelerated cell growth, cell migration and inhibited cell apoptosis, while knock-down of Axl exerted opposite effect. Axl expression was closely associated with serum AFP, multiple tumors, absence of encapsulation, microvascular invasion, and advanced BCLC or TNM stage. Patients with positive Axl staining had a higher 5year recurrence rate (92% vs. 71%, P
Axl Expression Stratifies Patients with Poor Prognosis after Hepatectomy for Hepatocellular Carcinoma Jian Liu1☯, Kui Wang1☯, Zhenlin Yan1☯, Yong Xia1, Jun Li1, Lehua Shi1, Qifei Zou1, Xuying Wan2, Binghua Jiao3, Hongyang Wang4, Mengchao Wu1,4, Yongjie Zhang5*, Feng Shen1*
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1 Department of Hepatic Surgery, the Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China, 2 Department of Clinical Database, the Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China, 3 Department of Biochemistry and Molecular Biology, Second Military Medical University, Shanghai, China, 4 National Scientific Center for Liver Cancer, Shanghai, China, 5 Department of Biliary Surgery, the Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China ☯ These authors contributed equally to this work. * [email protected] (FS); [email protected] (YZ)
OPEN ACCESS Citation: Liu J, Wang K, Yan Z, Xia Y, Li J, Shi L, et al. (2016) Axl Expression Stratifies Patients with Poor Prognosis after Hepatectomy for Hepatocellular Carcinoma. PLoS ONE 11(5): e0154767. doi:10.1371/journal.pone.0154767 Editor: William B. Coleman, University of North Carolina School of Medicine, UNITED STATES
Abstract Background Axl is a receptor tyrosine kinase which plays an important role in multiple human malignancies.
Received: January 10, 2015 Accepted: April 19, 2016
Design
Published: May 16, 2016
The Axl expression was examined in several hepatocellular carcinoma(HCC) cell lines, paired tumor and nontumorous samples. Then, we examined cell growth curve, cell apoptosis and cell migration in SMMC-7721 cells over-expressed with Axl or siRNA against Axl, respectively. Finally, the prognostic value of Axl was investigated in a prospective cohort of 246 consecutive HCC patients undergoing curative hepatoectomy.
Copyright: © 2016 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: This work was supported by grants from National Natural Science Foundation of China (grant number 81071867 to KW; grant number 30772141 to SF; grant number 30921006 to HYW); a grant from the State Key Project on Infectious Diseases of China (grant number 2012ZX10002 -011,016 to FS); and a grant of Shanghai Hospital Development Program (grant number SHDC12010121 to FS). Competing Interests: The authors have declared that no competing interests exist.
Results We found Axl was positive in 22% of examined tumor tissues and all four cell lines. Overexpressing Axl in SMMC-7721 cells accelerated cell growth, cell migration and inhibited cell apoptosis, while knock-down of Axl exerted opposite effect. Axl expression was closely associated with serum AFP, multiple tumors, absence of encapsulation, microvascular invasion, and advanced BCLC or TNM stage. Patients with positive Axl staining had a higher 5year recurrence rate (92% vs. 71%, P
