Expression of Human Leukocyte Antigen-G and Its Prognosis Value for Liver Transplant Patients with Hepatocellular Carcinoma_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

ZENG Xiancheng ^1,2 , CHEN Guanzhong ¹ , CHEN Wei ³ , ZHANG Tong ¹ , LI Hua ¹ , ZHANG Qi ¹ , CHEN Guihua. ¹

1. Transplantation Research Institute of Sun Yat-sen University, Liver Transplantation Center， TheThird Affiliated Hospital， Sun Yat-sen University， Guangzhou 510630， Guangdong Province， China;;
2. Department of General Surgery， Zengcheng People’s Hospital （Boji-Affiliated Hospital, Sun Yat-Sen University）， Zengcheng 511300,Guangdong Province， China;;

Corresponding author：

Keywords：

Hepatocellular carcinoma; Liver transplantation; Prognosis; Human leukocyte antigen-G; Immunohistochemistry

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Objective 　To investigate the expression of human leukocyte antigen-G （HLA-G） in hepatocellular carcinoma （HCC） tissues， and to evaluate the prognosis of patients after liver transplantation.
Methods 　The clinical data of 83 patients with HCC who underwent liver transplantation from January 2004 to May 2008 in the Liver Transplantation Center of the Third Affiliated Hospital of Sun Yat-sen University were analyzed retrospectively. The expression of HLA-G in HCC tissues was detected by using immunohistochemical analysis. The Kaplan-Meier method was used to evaluate the cumulative survival rate and tumor-free survival rate. Log-rank test and Cox regression model were used to analyze the single and muti-factor for tumor-free survival rate, respectively.
Results 　Among the 83 patients，there were tumor recurrence in 35 patients （42.2%）. The 1-year，3-year, and 5-year of cumulative survival rate was 97.2%，89.8%, and 43.1%, respectively. The 1-year，3-year， and 5-year of tumor-free survival rate was 93.6%，68.9%, and 38.7%, respectively. The positive rate （68.7%） of HLA-G expression in HCC tissues was significantly higher than that in paracancerous tissues （15.7%）, P＜0.01. A significant association was found between expression of HLA-G and tumor size， vascular invasion, and pathology differentiation （P＜0.05）. Single factor analysis showed that the expression of HLA-G （P＜0.01）， tumor size （P＜0.05）， vascular invasion （P＜0.01）， and pathology differentiation （P＜0.01） effected on tumor-free survival rates of HCC patients after liver transplantation. The tumor-free survival rate in positive expression of HLA-G group was significantly lower than that in negative expression of HLA-G group （P＜0.01）. Cox regression model analysis showed that the expression of HLA-G （P＜0.05）， vascular invasion （P＜0.01）， and pathology differentiation （P＜0.05） were independent risk factors that affected the tumor-free survival rate of HCC patients after liver transplantation.
Conclusions 　There is expression of HLA-G in HCC tissues. The independent risk factors that affecting the tumor-free survival rate of HCC patients after liver transplantation include the expression of HLA-G， vascular invasion, and pathological differentiation. Taking interferential measures for patients with positive expression of HLA-G and strict selection of indication of liver transplantation for HCC can reduce the recurrence rate of tumor.

Citation： ZENG Xiancheng,CHEN Guanzhong,CHEN Wei,ZHANG Tong,LI Hua,ZHANG Qi,CHEN Guihua.. Expression of Human Leukocyte Antigen-G and Its Prognosis Value for Liver Transplant Patients with Hepatocellular Carcinoma. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2012, 19(7): 712-717. doi: Copy

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1. Le Bouteiller P. HLA-G in the human placenta：expression and potential functions [J]. Biochem Soc Trans， 2000， 28(2)：208-212.
2. Chang CC， Campoli M， Ferrone S. HLA classⅠantigen expression in malignant cells：why does it not always correlate with CTL-mediated lysis [J]. Curr Opin Immunol， 2004， 16(5)：644-650.
3. 曾宪成，张彤，李华，等． RNA 干扰白细胞抗原-G 增强自然杀伤细胞对肝癌的免疫监视 [J]．中华实验外科杂志， 2009，26(8)： 991-994．.
4. Pang RW， Joh JW， Johnson PJ， et al. Biology of hepatocelular carcima [J]. Ann Surg Oncol， 2008， 15(4)：962-971.
5. CLTR. 2009 Annual Scientific Report：liver transplantation for hepatocellular carcinoma [R]. CLTR，China. www. cltr. org.[6] Alsina AE. Liver transplantation for hepatocellular carcinoma[J]. Cancer Control， 2010， 17(2)：83-86.
6. 张荣生，王轩，张斌，等．肝癌肝移植术后复发的危险因素分析 [J]．中国普外基础与临床杂志， 2011， 18(1)： 29-32．.
7. Yao FY. Liver transplantation for hepatocellular carcinoma：beyond the Milan criteria [J]. Am J Transplant， 2008， 8(10)：1982-1989.
8. Guiteau JJ， Cotton RT， Washburn WK， et al. An early regional experience with expansion of Milan Criteria for liver transplant recipients [J]. Am J Transplant， 2010， 10(9)：2092-2098.
9. Cillo U， Vitale A， Bassanello M， et al. Liver transplantation for the treatment of moderately or well-differentiated hepatocellular carcinoma [J]. Ann Surg， 2004， 239(2)：150-159.
10. Cillo U， Vitale A， Grigoletto F， et al. Intention-to-treat analysis of liver transplantation in selected， aggressive treated HCC patients exceeding the Milan criteria [J]. Am J Transplant， 2007，7(4)：972-981.
11. Rouas-Freiss N， Moreau P， Ferrone S， et al. HLA-G proteins in cancer：do they provide tumor cells with an escape mechanism [J]. Cancer Res， 2005， 65(22)：10139-10144.
12. Chen HX， Lin A， Shen CJ， et al. Upregulation of human leukocyte antigen-G expression and its clinical significance in ductal breast cancer [J]. Hum Immunol， 2010， 71(9)：892-898.
13. Du L， Xiao X， Wang C， et al. Human leukocyte antigen-G is closely associated with tumor immune escape in gastric cancer by increasing local regulatory T cells [J]. Cancer Sci， 2011，102(7)：1272-1280.
14. Cao M， Yie SM， Liu J， et al. Plasma soluble HLA-G is a potential biomarker for diagnosis of colorectal， gastric， esophageal and lung cancer [J]. Tissue Antigens， 2011， 78(2)：120-128.
15. Hanak L， Slaby O， Lauerova L， et al. Expression pattern of HLA classⅠantigens in renal cell carcinoma and primary cell line cultures：methodological implications for immunotherapy [J].Med Sci Monit， 2009， 15(12)：CR638-CR643.
16. Urosevic M， Kurrer MO， Kamarashev J， et al. Human leukocyte antigen G up-regulation in lung cancer associates with highgrade histology， human leukocyte antigen classⅠ lossand interleukin-10 production [J]. Am J Pathol， 2001， 159(3)：817-824.
17. Gomez GG， Kruse CA. Cellular and functional characterization of immunoresistant human glioma cell clones selected with alloreactive cytotoxic T lymphocytes reveals their up-regulated synthesis of biologically active TGF-beta [J]. J Immunother，2007， 30(3)：261-273.
18. Amiot L， Le Friec G， Sebti Y， et al. HLA-G and lymphoproliferative disorders [J]. Semin Cancer Biol， 2003， 13(5)：379-385.
19. Rebmann V， Busemann A， Lindemann M， et al. Detection of HLA-G5 secreting cells [J]. Hum Immunol， 2003， 64(11)：1017-1024.
20. Yan W， Zhou Y， Meng XQ， et al. Expression of HLA-G in patients with hepatocellular carcinoma [J]. Hepatobiliary Pancreat Dis Int， 2011， 10(2)：158-163.
21. Schütt P， Schütt B， Switala M， et al. Prognostic relevance of soluble human leukocyte antigen-G and total human leukocyte antigen classⅠmolecules in lung cancer patients [J]. Hum Immunol，2010， 71(5)：489-495.
22. Mach P， Blecharz P， Basta P， et al. Differences in the soluble HLA-G blood serum concentration levels in patients with ovarian cancer and ovarian and deep endometriosis [J]. Am J Reprod Immunol， 2010， 63(5)：387-395.
23. R Guimarães MC， Soares CP， Donadi EA， et al. Low expression of human histoco-mpatibility soluble leukocyte antigen-G (HLA-G5) in invasive cervical cancer with and without metastasis，associated with papilloma virus (HPV) [J]. J Histochem Cytochem， 2010， 58(5)：405-411.
24. de Kruijf EM， Sajet A， van Nes JG， et al. HLA-E and HLA-G expression in classical HLA classⅠ-negative tumors is of prognotic value for clinical outcome of early breast cancer patients [J].J Immunol， 2010， 185(12)：7452-7459.
25. Jung YW， Kim YT， Kim SW， et al. Correlation of human leukocyte antigen-G (HLA-G) expression and disease progression in epithelial ovarian cancer [J]. Reproductive Sciences， 2009，16(11)：1103-1111.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Expression of Human Leukocyte Antigen-G and Its Prognosis Value for Liver Transplant Patients with Hepatocellular Carcinoma

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