Association between the expression of somatostatin receptors and pathological features, prognosis in hepatocellular carcinoma
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摘要: 目的研究生长抑素受体(SSTR)在肝细胞癌组织中表达水平及其与肝细胞癌临床病理特征及预后的关系。方法所有肝细胞癌标本取自2012年7月-2014年12月就诊于解放军第三医院及大连医科大学附属二院肝胆科行切除术后经病理组织学检查证实为HCC的患者(n=80,试验组),另选取同期疑似肝部疾病且行肝穿刺确诊的非肝细胞癌患者(n=80,对照组)。采用RT-PCR检测SSTR-2、SSTR-3 mRNA水平,采用免疫组化检测SSTR-2、SSTR-3蛋白表达的水平。计量资料组间比较采用t检验,计数资料组间比较采用χ2检验,Kaplan-Meier法分析患者生存情况,Cox分析肝细胞癌患者预后的影响因素。结果对照组SSTR-2、SSTR-3 mRNA及蛋白均显著高于试验组(t值分别为6.456、8.128,χ2值分别为7.992、9.157,P值均<0.05)。单因素分析显示,SSTR-2和SSTR-3 mRNA与肿瘤结节(t=6.533、5.041,P值均<0.05)、分化程度(t=4.672、4.013,P值均<0.05)、浸润深度(t=6.735、7.019,P值均<...Abstract: Objective To investigate the expression of somatostatin receptors (SSTRs) in hepatocellular carcinoma (HCC) tissue and its association with clinicopathological features and prognosis of HCC.Methods HCC samples were collected from 80 patients who visited Third Hospital of PLA and Department of Hepatobiliary Surgery in The Second Affiliated Hospital of Dalian Medical University and who underwent hepatectomy from July 2012 to December 2014 and were diagnosed with HCC based on postoperative pathology (trial group) .Another 80 patients who were suspected of liver disease and were not diagnosed with HCC by liver biopsy were enrolled as control group.RT-PCR and immunohistochemistry were used to measure the mRNA and protein expression of SSTR-2 and SSTR-3.The t-test was used for comparison of continuous data between groups, the chi-square test was used for comparison of categorical data between groups, the Kaplan-Meier method was used to analyze patients' survival, and the Cox regression analysis was used to investigate the influencing factors for the prognosis of HCC patients.Results The control group had significantly higher mRNA and protein expression of SSTR-2 and SSTR-3 than the trial group (t = 6.456 and 8.128, χ2= 7.992 and 9.157, all P < 0.05) .The univariate analysis showed that the mRNA expression of SSTR-2 and SSTR-3 was significantly correlated with tumor nodule (t = 6.533 and 5.041, both P < 0.05) , degree of tumor differentiation (t = 4.672 and 4.013, both P < 0.05) , depth of infiltration (t = 6.735 and 7.019, both P < 0.05) , viral hepatitis (t = 4.929 and4.535, both P < 0.05) , alcoholic hepatitis (t = 4.032 and 4.362, both P < 0.05) , and diabetes (t = 4.372 and 6.293, both P < 0.05) , and the protein expression of SSTR-2 and SSTR-3 was significantly correlated with tumor nodule (χ2= 25.223 and 15.399, both P <0.05) , degree of tumor differentiation (χ2= 7.535 and 10.944, both P < 0.05) , and depth of infiltration (χ2= 22.520 and 9.968, both P< 0.05) .Compared with the group with positive expression of SSTR-2 and SSTR-3, the group with negative expression had significantly lower cumulative postoperative disease-free survival rate (P = 0.015 and 0.004) and postoperative overall survival rate (P = 0.009 and <0.001) .The Cox model analysis showed that protein expression of SSTR-2 and SSTR-3, the number of tumor nodules, liver cirrhosis, and vein infiltration in HCC tissue were independent risk factors for overall survival after HCC surgery (P < 0.05) .Conclusion HCC patients have lower expression of SSTR-2 and SSTR-3 than non-HCC patients, and such low expression is closely associated with invasion/metastasis and poor prognosis of HCC.SSTRs may be the markers for the prognosis of HCC.
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Key words:
- receptors, somatostatin /
- carcinoma, hepatocellular /
- prognosis /
- risk factors
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[1]JI R, DOU KF, XU H.Prevention and mangement of recurrence metastasis of hepatocellular carcinoma after liver transplantation[J].J Clin Hepatol, 2014, 30 (1) :7-10. (in Chinese) 季茹, 窦科峰, 许辉.肝细胞癌患者肝移植术后肿瘤复发转移的防治[J].临床肝胆病杂志, 2014, 30 (1) :7-10. [2]JIAO ZY, YU ZY.Surgical treatment of primary liver cancer:progress and prospects[J/CD].Chin J Hepatic Surg:Electronic Edition, 2016, 5 (5) :281-284. (in Chinese) 焦作义, 俞泽元.原发性肝癌外科治疗进展[J/CD].中华肝脏外科手术学电子杂志, 2016, 5 (5) :281-284. [3]AYUB A, ASHFAQ UA, HAQUE A.HBV induced HCC:major risk factors from genetic to molecular level[J].Biomed Res Int, 2013, 2013:810461. [4]SUN B, KARIN M.Obesity, inflammation, and liver cancer[J].J Hepatol, 2012, 56 (3) :704-713. [5]RIDNOUR LA, CHENG RY, SWITZER CH, et al.Molecular pathways:toll-like receptors in the tumor microenvironment——poor prognosis or new therapeutic opportunity[J].Clin Cancer Res, 2013, 19 (6) :1340-1346. [6]MIZUTANI G, NAKANISHI Y, WATANABE N, et al.Expression of somatostatin receptor (SSTR) subtypes (SSTR-1, 2A, 3, 4and 5) in neuroendocrine tumors using real-time RT-PCR Method and immunohistochemistry[J].Acta Histochem Cytochem, 2012, 45 (3) :167-176. [7]WANG L, TANG K, ZHANG Q, et al.Somatostatin receptorbased molecular imaging and therapy for neuroendocrine tumors[J].Biomed Res Int, 2013, 2013 (6) :102819. [8]PENG Y, DENG L, DING Y, et al.Comparative study of somatostatin-human serum albumin fusion proteins and natural somatostatin on receptor binding, internalization and activation[J].PLo S One, 2014, 9 (2) :e89932. [9]SUNL C, COY DH.Somatostatin receptor-targeted anti-cancer therapy[J].Curr Drug Deliv, 2011, 8 (1) :2-10. [10]HU CY, YI CQ.Effect of Human SSTR 3 gene on growth of gastric cancer cells[J].Chin J Clin Gastroenterol, 2005, 17 (6) :282-285. (in Chinese) 呼闯营, 易粹琼.生长抑素受体SSTR 3基因对胃癌细胞生长的影响[J].临床消化病杂志, 2005, 17 (6) :282-285. [11]LEQUOY M, DESBOIS-MOUTHON C, WENDUM D, et al.Somatostatin receptors in resected hepatocellular carcinoma:status and correlation with markers of poor prognosis[J].Histopathology, 2017, 70 (3) :492-498. [12]ABDEL-RAHMAN O, LAMARCA A, VALLE JW, et al.Somatostatin receptor expression in hepatocellular carcinoma:prognostic and therapeutic considerations[J].Endocr Relat Cancer, 2014, 21 (6) :r485-r493. [13]ZHAO WC, ZHANG HB, YANG N, et al.Preoperative predictors of short-term survival after hepatectomy for multinodular hepatocellular carcinoma[J].World J Gastroenterol, 2012, 18 (25) :3272-3281. [14]TWAIJ A, PUCHER PH, SODERGREN MH, et al.Laparoscopic vs open approach to resection of hepatocellular carcinoma in patients with known cirrhosis:systematic review and meta-analysis[J].World J Gastroenterol, 2014, 20 (25) :8274-8281. [15]ZHAO ZY, XI QY, ZHANG YL.Physiological function and kinetic characteristics of somatostatin receptors[J].Chin J Biochem Mol Biol, 2010, 26 (6) :517-522. (in Chinese) 赵增阳, 习欠云, 张永亮.生长抑素受体的生理功能及动力学特征[J].中国生物化学与分子生物学报, 2010, 26 (6) :517-522. [16]LIU Y, JIANG L, MU L.Somatostatin receptor subtypes 2 and 5 are associated with better survival in operable hepatitis B-related hepatocellular carcinoma following octreotide long-acting release treatment[J].Oncol Lett, 2013, 6 (3) :821-828.
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