Expression of IL-26 predicts prognosis of patients with hepatocellular carcinoma after surgical resection
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摘要
Background: There is no data regarding prognostic impact of interleukin(IL)-26 on outcomes of patients with hepatocellular carcinoma(HCC). The present study aimed to evaluate the prognostic impact of IL-26 on HCC patients undergoing liver resection. Methods: From 2003 to 2008, 122 patients with HCC who received surgical curative resection were enrolled. Patients were stratified into IL-26-upper and-lower groups according to the median expression level from immunohistochemical staining of resected specimens. Prognostic impact of IL-26 was estimated using Kaplan–Meier curves. Univariate and multivariate analyses were performed to evaluate timedependent prognostic impact and independency of IL-26. Demographic and clinical factors that were associated with IL-26 were comprehensively identified. Results: Prognosis of the patients with high level of IL-26 revealed to be significantly unfavorable in both cumulative recurrence-free survival( P < 0.001) and overall survival( P = 0.002). Upper expression of IL-26(HR: 1.643; 95% CI: 1.021 to 2.644; P = 0.041) and microvascular invasion(HR: 3.303; 95% CI: 1.255 to 8.696; P = 0.016) were identified as significant independent prognostic factors for overall survival in the multivariable analysis. Conclusions: IL-26 is a novel prognostic factor for HCC after resection. Evaluation of IL-26 expression may be potentially valuable in clinical therapy when planning individualized follow-up schedule and evaluating candidates for prophylactic adjuvant treatment to prevent recurrence.
Background: There is no data regarding prognostic impact of interleukin(IL)-26 on outcomes of patients with hepatocellular carcinoma(HCC). The present study aimed to evaluate the prognostic impact of IL-26 on HCC patients undergoing liver resection. Methods: From 2003 to 2008, 122 patients with HCC who received surgical curative resection were enrolled. Patients were stratified into IL-26-upper and-lower groups according to the median expression level from immunohistochemical staining of resected specimens. Prognostic impact of IL-26 was estimated using Kaplan–Meier curves. Univariate and multivariate analyses were performed to evaluate timedependent prognostic impact and independency of IL-26. Demographic and clinical factors that were associated with IL-26 were comprehensively identified. Results: Prognosis of the patients with high level of IL-26 revealed to be significantly unfavorable in both cumulative recurrence-free survival( P < 0.001) and overall survival( P = 0.002). Upper expression of IL-26(HR: 1.643; 95% CI: 1.021 to 2.644; P = 0.041) and microvascular invasion(HR: 3.303; 95% CI: 1.255 to 8.696; P = 0.016) were identified as significant independent prognostic factors for overall survival in the multivariable analysis. Conclusions: IL-26 is a novel prognostic factor for HCC after resection. Evaluation of IL-26 expression may be potentially valuable in clinical therapy when planning individualized follow-up schedule and evaluating candidates for prophylactic adjuvant treatment to prevent recurrence.
Background: There is no data regarding prognostic impact of interleukin(IL)-26 on outcomes of patients with hepatocellular carcinoma(HCC). The present study aimed to evaluate the prognostic impact of IL-26 on HCC patients undergoing liver resection. Methods: From 2003 to 2008, 122 patients with HCC who received surgical curative resection were enrolled. Patients were stratified into IL-26-upper and-lower groups according to the median expression level from immunohistochemical staining of resected specimens. Prognostic impact of IL-26 was estimated using Kaplan–Meier curves. Univariate and multivariate analyses were performed to evaluate timedependent prognostic impact and independency of IL-26. Demographic and clinical factors that were associated with IL-26 were comprehensively identified. Results: Prognosis of the patients with high level of IL-26 revealed to be significantly unfavorable in both cumulative recurrence-free survival( P < 0.001) and overall survival( P = 0.002). Upper expression of IL-26(HR: 1.643; 95% CI: 1.021 to 2.644; P = 0.041) and microvascular invasion(HR: 3.303; 95% CI: 1.255 to 8.696; P = 0.016) were identified as significant independent prognostic factors for overall survival in the multivariable analysis. Conclusions: IL-26 is a novel prognostic factor for HCC after resection. Evaluation of IL-26 expression may be potentially valuable in clinical therapy when planning individualized follow-up schedule and evaluating candidates for prophylactic adjuvant treatment to prevent recurrence.
引文
[1] Forner A, Reig M, Bruix J. Hepatocellular carcinoma. Lancet2018;391:1301-1314.
[2] Fujiwara N, Friedman SL, Goossens N, Hoshida Y. Risk factors and prevention of hepatocellular carcinoma in the era of precision medicine. J Hepatol2018;68:526-549.
[3] Ayuso C, Rimola J, Vilana R, Burrel M, Darnell A, Garcia-Criado A, et al. Diagnosis and staging of hepatocellular carcinoma(HCC):current guidelines. Eur J Radiol 2018;101:72-81.
[4] Llovet JM, Montal R, Sia D, Finn RS. Molecular therapies and precision medicine for hepatocellular carcinoma. Nat Rev Clin Oncol 2018;15:599-616.
[5] Menahem B, Lubrano J, Duvoux C, Mulliri A, Alves A, Costentin C, et al. Liver transplantation versus liver resection for hepatocellular carcinoma in intention to treat:an attempt to perform an ideal meta-analysis. Liver Transpl2017;23:836-844.
[6] Rich NE, Parikh ND, Singal AG. Hepatocellular carcinoma and liver transplantation:changing patterns and practices. Curr Treat Options Gastroenterol2017;15:296-304.
[7] Rudnick SR, Russo MW. Liver transplantation beyond or downstaging within the Milan criteria for hepatocellular carcinoma. Expert Rev Gastroenterol Hepatol 2018;12:265-275.
[8] Hu L, Xue F, Li Y, Shao M, Sun Y, Wei G. A long-term follow-up and comprehensive observation of risk and prognosis factors of recurrence and survival after resection of hepatocellular carcinoma. Cell Biochem Biophys2014;69:421-431.
[9] Hsu CY, Liu PH, Ho SY, Hsia CY, Kudaravalli P, Lee YH, et al. Using nomogram of the Barcelona clinic liver cancer system for treatment selection in patients with stage C hepatocellular carcinoma. BMC Cancer 2018; 18:289.
[10] Chen ZH, Hong YF, Chen X, Chen J, Lin Q, Lin J, et al. Comparison of five staging systems in predicting the survival rate of patients with hepatocellular carcinoma undergoing trans-arterial chemoembolization therapy. Oncol Lett2018;15:855-862.
[11] Sha M, Jeong S, Chen XS, Tong Y, Cao J, Sun HY, et al. Expression of VEGFR-3 in intrahepatic cholangiocarcinoma correlates with unfavorable prognosis through lymphangiogenesis. Int J Biol Sci 2018;14:1333-1342.
[12] Fan ST. Hepatocellular carcinoma-resection or transplant. Nat Rev Gastroenterol Hepatol. 2012 Dec;9(12):732-737.
[13] Gingold JA, Zhu D, Lee DF, Kaseb A, Chen J. Genomic profiling and metabolic homeostasis in primary liver cancers. Trends Mol Med 2018;24:395-411.
[14] Fu J, Wang H. Precision diagnosis and treatment of liver cancer in China. Cancer Lett 2018:412:283-288.
[15] Mehta AS, Lau DT, Wang M, Islam A, Nasir B, Javaid A, et al. Application of the Doylestown algorithm for the early detection of hepatocellular carcinoma.PLoS One 2018;13:e0203149.
[16] Bao H, Su H. Long noncoding RNAs act as novel biomarkers for hepatocellular carcinoma:progress and prospects. Biomed Res Int 2017;2017:6049480.
[17] Selcuk H. Prognostic factors and staging systems in hepatocellular carcinoma.Exp Clin Transp 2017;15:45-49.
[18] Fujii M, Nishida A, Imaeda H, Ohno M, Nishino K, Sakai S, et al. Expression of Interleukin-26 is upregulated in inflammatory bowel disease. World J Gastroenterol 2017;23:5519-5529.
[19] Tengvall S, Che KF, Linden A. Interleukin-26:an emerging player in host defense and inflammation. J Innate Immun 2016;8:15-22.
[20] Jeong S, Zheng B, Wang H, Xia Q, Chen L. Nervous system and primary liver cancer. Biochim Biophys Acta Rev Cancer 2018;1869:286-292.
[21] Ringelhan M, Pfister D, O'Connor T, Pikarsky E, Heikenwalder M. The immunology of hepatocellular carcinoma. Nat Immunol 2018;19:222-232.
[22] Miot C, Beaumont E, Duluc D, Le Guillou-Guillemette H, Preisser L, Garo E,et al. IL-26 is overexpressed in chronically HCV-infected patients and enhances TRAIL-mediated cytotoxicity and interferon production by human NK cells. Gut2015;64:1466-1475.
[23] Huang JL, Fu YP, Jing CY, Yi Y, Sun J, Gan W, et al. A novel and validated prognostic nomogram based on liver fibrosis and tumor burden for patients with hepatocellular carcinoma after curative resection. J Surg Oncol2018:117:625-633.
[24] Kim Y, Park HC, Yoon SM, Kim TH, Lee J, Choi J, et al. Prognostic group stratification and nomogram for predicting overall survival in patients who received radiotherapy for abdominal lymph node metastasis from hepatocellular carcinoma:a multi-institutional retrospective study(KROG 15-02). Oncotarget2017;8:94450-94461.
[25] Zhang W, Tan Y, Shen S, Jiang L, Yan L, Yang J, et al. Prognostic nomogram for hepatocellular carcinoma in adolescent and young adult patients after hepatectomy. Oncotarget 2017;8:106393-106404.
[2] Fujiwara N, Friedman SL, Goossens N, Hoshida Y. Risk factors and prevention of hepatocellular carcinoma in the era of precision medicine. J Hepatol2018;68:526-549.
[3] Ayuso C, Rimola J, Vilana R, Burrel M, Darnell A, Garcia-Criado A, et al. Diagnosis and staging of hepatocellular carcinoma(HCC):current guidelines. Eur J Radiol 2018;101:72-81.
[4] Llovet JM, Montal R, Sia D, Finn RS. Molecular therapies and precision medicine for hepatocellular carcinoma. Nat Rev Clin Oncol 2018;15:599-616.
[5] Menahem B, Lubrano J, Duvoux C, Mulliri A, Alves A, Costentin C, et al. Liver transplantation versus liver resection for hepatocellular carcinoma in intention to treat:an attempt to perform an ideal meta-analysis. Liver Transpl2017;23:836-844.
[6] Rich NE, Parikh ND, Singal AG. Hepatocellular carcinoma and liver transplantation:changing patterns and practices. Curr Treat Options Gastroenterol2017;15:296-304.
[7] Rudnick SR, Russo MW. Liver transplantation beyond or downstaging within the Milan criteria for hepatocellular carcinoma. Expert Rev Gastroenterol Hepatol 2018;12:265-275.
[8] Hu L, Xue F, Li Y, Shao M, Sun Y, Wei G. A long-term follow-up and comprehensive observation of risk and prognosis factors of recurrence and survival after resection of hepatocellular carcinoma. Cell Biochem Biophys2014;69:421-431.
[9] Hsu CY, Liu PH, Ho SY, Hsia CY, Kudaravalli P, Lee YH, et al. Using nomogram of the Barcelona clinic liver cancer system for treatment selection in patients with stage C hepatocellular carcinoma. BMC Cancer 2018; 18:289.
[10] Chen ZH, Hong YF, Chen X, Chen J, Lin Q, Lin J, et al. Comparison of five staging systems in predicting the survival rate of patients with hepatocellular carcinoma undergoing trans-arterial chemoembolization therapy. Oncol Lett2018;15:855-862.
[11] Sha M, Jeong S, Chen XS, Tong Y, Cao J, Sun HY, et al. Expression of VEGFR-3 in intrahepatic cholangiocarcinoma correlates with unfavorable prognosis through lymphangiogenesis. Int J Biol Sci 2018;14:1333-1342.
[12] Fan ST. Hepatocellular carcinoma-resection or transplant. Nat Rev Gastroenterol Hepatol. 2012 Dec;9(12):732-737.
[13] Gingold JA, Zhu D, Lee DF, Kaseb A, Chen J. Genomic profiling and metabolic homeostasis in primary liver cancers. Trends Mol Med 2018;24:395-411.
[14] Fu J, Wang H. Precision diagnosis and treatment of liver cancer in China. Cancer Lett 2018:412:283-288.
[15] Mehta AS, Lau DT, Wang M, Islam A, Nasir B, Javaid A, et al. Application of the Doylestown algorithm for the early detection of hepatocellular carcinoma.PLoS One 2018;13:e0203149.
[16] Bao H, Su H. Long noncoding RNAs act as novel biomarkers for hepatocellular carcinoma:progress and prospects. Biomed Res Int 2017;2017:6049480.
[17] Selcuk H. Prognostic factors and staging systems in hepatocellular carcinoma.Exp Clin Transp 2017;15:45-49.
[18] Fujii M, Nishida A, Imaeda H, Ohno M, Nishino K, Sakai S, et al. Expression of Interleukin-26 is upregulated in inflammatory bowel disease. World J Gastroenterol 2017;23:5519-5529.
[19] Tengvall S, Che KF, Linden A. Interleukin-26:an emerging player in host defense and inflammation. J Innate Immun 2016;8:15-22.
[20] Jeong S, Zheng B, Wang H, Xia Q, Chen L. Nervous system and primary liver cancer. Biochim Biophys Acta Rev Cancer 2018;1869:286-292.
[21] Ringelhan M, Pfister D, O'Connor T, Pikarsky E, Heikenwalder M. The immunology of hepatocellular carcinoma. Nat Immunol 2018;19:222-232.
[22] Miot C, Beaumont E, Duluc D, Le Guillou-Guillemette H, Preisser L, Garo E,et al. IL-26 is overexpressed in chronically HCV-infected patients and enhances TRAIL-mediated cytotoxicity and interferon production by human NK cells. Gut2015;64:1466-1475.
[23] Huang JL, Fu YP, Jing CY, Yi Y, Sun J, Gan W, et al. A novel and validated prognostic nomogram based on liver fibrosis and tumor burden for patients with hepatocellular carcinoma after curative resection. J Surg Oncol2018:117:625-633.
[24] Kim Y, Park HC, Yoon SM, Kim TH, Lee J, Choi J, et al. Prognostic group stratification and nomogram for predicting overall survival in patients who received radiotherapy for abdominal lymph node metastasis from hepatocellular carcinoma:a multi-institutional retrospective study(KROG 15-02). Oncotarget2017;8:94450-94461.
[25] Zhang W, Tan Y, Shen S, Jiang L, Yan L, Yang J, et al. Prognostic nomogram for hepatocellular carcinoma in adolescent and young adult patients after hepatectomy. Oncotarget 2017;8:106393-106404.
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