肝癌组织IFITM3蛋白表达水平及其与肝细胞癌患者手术切除术后肝内肿瘤复发的相关性分析
|
摘要
目的探讨肝细胞癌(HCC)组织干扰素诱导跨膜蛋白3(IFITM3)表达水平及其临床意义。方法在我院接受根治性手术切除治疗的43例HCC患者,术中取癌组织和癌旁肝组织,分别采用Western blot法和免疫组化法检测组织IFITM3蛋白表达情况,比较肝内肿瘤复发与未复发患者癌组织IFITM3表达的差异。结果经Western blot法检测肝癌组织IFITM3表达水平为(1.2386±0.1901),显著高于癌旁组织的(0.9496±0.0995,t=8.832,P=0.000);免疫组化法检测显示肝癌组织IFITM3蛋白阳性率为72.1%(31/43),明显高于癌旁组织的14.0%(6/43,x~2=29.647,P=0.000);中分化肝癌组织IFITM3蛋白阳性率为90.9%(10/11),低分化肝癌组织为95.2%(20/21),均明显高于高分化组的9.1%(1/11)(x~2=14.727, P=0.000;x~2=23.748,P=0.000);术后复发组癌组织IFITM3蛋白阳性率为81.0%(17/21),未复发组为22.7%(5/22),两者比较差异具有统计学意义(x~2=14.578,P=0.000)。结论 HCC组织IFITM3蛋白呈高表达,且肝癌分化越差,IFITM3表达也越强,并可能与术后肿瘤复发有关。
Objective To investigate the expression of interferon-induced transmembrane protein (IFITM3) in hepatocellular carcinoma (HCC) and its correlation with intrahepatic tumor recurence after hepatectomy.Methods A total of 43 patients with HCC were recruited in our hospital,and all of them received hepatectomy.The specimens of cancer and its adjacent liver tissues were taken,and the expression of IFITM3 was detected by Western blot and by immunohistochemistry. All the patients were followed-up for 1 years. Results The expression of IFITM3 protein in HCC tissues was (1.2386±0.1901),significantly stronger than (0.9496±0.0995) in the adjacent tissues (t=8.832,P=0.000);the results of immunohistochemical staining showed that the brownish yellow granular IFITM3 protein located in the cytoplasm of liver cancer tissues and adjacent tissues,and the positive rate of IFITM3 protein in hepatocellular carcinoma was 72.1% (31/43),significantly higher than 14.0% (6/43) in adjacent tissues (x~2=29.647,P =0.000);the positive rate of IFITM protein in low and medium differentiated HCC tissues were 95.2% (20/21) and 90.9% (10/11),significantly higher than 9.1% (1/11) in high differentiated group (x~2=14.727,P=0.000;x~2=23.748,P=0.000);the positive rate of IFITM3 protein in patients with recurrent intrahepatic tumor was 81.0% (17/21),much higher than 22.7% (5/22) in without tumor recurrence (x~2=14.578,P=0.000).Conclusion IFITM3 protein is highly expressed in HCC tissues,and the worse the differentiation of HCC,the stronger the degree of expression,which might closely be related to the recurrence of HCC after hepatectomy.
Objective To investigate the expression of interferon-induced transmembrane protein (IFITM3) in hepatocellular carcinoma (HCC) and its correlation with intrahepatic tumor recurence after hepatectomy.Methods A total of 43 patients with HCC were recruited in our hospital,and all of them received hepatectomy.The specimens of cancer and its adjacent liver tissues were taken,and the expression of IFITM3 was detected by Western blot and by immunohistochemistry. All the patients were followed-up for 1 years. Results The expression of IFITM3 protein in HCC tissues was (1.2386±0.1901),significantly stronger than (0.9496±0.0995) in the adjacent tissues (t=8.832,P=0.000);the results of immunohistochemical staining showed that the brownish yellow granular IFITM3 protein located in the cytoplasm of liver cancer tissues and adjacent tissues,and the positive rate of IFITM3 protein in hepatocellular carcinoma was 72.1% (31/43),significantly higher than 14.0% (6/43) in adjacent tissues (x~2=29.647,P =0.000);the positive rate of IFITM protein in low and medium differentiated HCC tissues were 95.2% (20/21) and 90.9% (10/11),significantly higher than 9.1% (1/11) in high differentiated group (x~2=14.727,P=0.000;x~2=23.748,P=0.000);the positive rate of IFITM3 protein in patients with recurrent intrahepatic tumor was 81.0% (17/21),much higher than 22.7% (5/22) in without tumor recurrence (x~2=14.578,P=0.000).Conclusion IFITM3 protein is highly expressed in HCC tissues,and the worse the differentiation of HCC,the stronger the degree of expression,which might closely be related to the recurrence of HCC after hepatectomy.
引文
[1]毛一雷,徐海峰.原发性肝细胞癌的早期诊断.中华内科杂志,2014,53(7):508-510.
[2]谭凯,杜锡林,杨涛,等.手术切除、肝动脉化疗栓塞、微波固化联合门静脉化疗对肝细胞癌术后复发的疗效分析.中华肝胆外科杂志,2014,20(4):253-257.
[3]李果,吴黎雳,宦宏波,等.肝细胞癌肝外转移对患者生存预后的影响.中华解剖与临床杂志,2014,19(4):307-309.
[4]Hu J,Wang S,Zhao Y,et al.Mechanism and biological significance of the overexpression of IFITM3 in gastric cancer.Oncol Rep,2014,32(6):2648-2656.
[5]Jia Y,Zhang M,Jiang W,et al.Overexpression of IFITM3 predicts the high risk of lymphatic metastatic recurrence in pN0esophageal squamous cell carcinoma after Ivor-Lewis esophagectomy.Peerj,2015;3:e1355.
[6]Nakajima A,Ibi D,Nagai T,et al.Induction of interferon-induced transmembrane protein 3 gene expression by lipopolysaccharide in astrocytes.Eur J Pharmacol,2014,745:166-175.
[7]Mcmichael TM,Zhang L,Chemudupati M,et al.The palmitoyltransferase ZDHHC20 enhances interferon-induced transmembrane protein 3(IFITM3)palmitoylation and antiviral activity.JBiol Chem,2017,292(52):21517-21526.
[8]贾户亮,钦伦秀.肝细胞癌术后复发的预测与预防策略.中华肝脏病杂志,2016,24(5):330-334.
[9]王浩,周岩冰,牛兆建,等.早期胃癌预后及复发转移因素分析.中华普通外科杂志,2015,30(8):639-642.
[10]丛文铭.肝癌复发转移的分子机制与病理学评估策略.中华肝脏病杂志,2016,24(5):324-326.
[11]Mills TC,Rautanen A,Elliott KS,et al.IFITM3 and susceptibility to respiratory viral infections in the community.J Infet Dis,2014,209:1028-1031.
[12]Yu M,Qi W,Huang Z,et al.Expression profile and histological distribution of IFITM1 and IFITM3 during H9N2 avian influenza virus infection in BALB/c mice.Med Microbiol Immunol,2015,204(4):505-514.
[13]Bailey CC,Kondur HR,Huang I,et al.Interferon-induced transmembrane protein 3 is a type II transmembrane protein.J Biol Chem,2013,288(45):32184-32193.
[14]Xu J,Qian P,Wu Q,et al.Swine interferon-induced transmembrane protein,s IFITM3,inhibits foot-and-mouth disease virus infection in vitro and in vivo.Antiviral Res,2014,109(9):22-29.
[15]Narayana SK,Helbig KJ,Mccartney EM,et al.The interferon-induced transmembrane proteins,IFITM1,IFITM2,and I-FITM3 inhibit hepatitis C virus entry.J Biol Chem,2015,290(43):25946-25959.
[16]Eltanani MK,Jin D,Campbell FC,et al.Interferon-induced transmembrane 3 binds osteopontin in vitro:expressed in vivo I-FITM3 reduced OPN expression.Oncogene,2010,29(5):752-62.
[17]万佳,张硕,李阿茜,等.干扰素诱导的跨膜蛋白IFITM1/2/3对SFTS病毒感染的影响.中华实验和临床病毒学杂志,2016,30(3):279-282.
[18]Li D,Peng Z,Tang H,et al.KLF4-mediated negative regulation of IFITM3 expression plays a critical role in colon cancer pathogenesis.Clin Cancer Res,2011,17(11):3558-3568.
[19]Zhao B,Wang H,Zong G,et al.The role of IFITM3 in the growth and migration of human glioma cells.BMC Neurol,2013,13(1):210.
[20]Zhang D,Wang H,He H,et al.Interferon induced transmembrane protein 3 regulates the growth and invasion of human lung adenocarcinoma.Thoracic Cancer,2017,8(4):337-343.
[2]谭凯,杜锡林,杨涛,等.手术切除、肝动脉化疗栓塞、微波固化联合门静脉化疗对肝细胞癌术后复发的疗效分析.中华肝胆外科杂志,2014,20(4):253-257.
[3]李果,吴黎雳,宦宏波,等.肝细胞癌肝外转移对患者生存预后的影响.中华解剖与临床杂志,2014,19(4):307-309.
[4]Hu J,Wang S,Zhao Y,et al.Mechanism and biological significance of the overexpression of IFITM3 in gastric cancer.Oncol Rep,2014,32(6):2648-2656.
[5]Jia Y,Zhang M,Jiang W,et al.Overexpression of IFITM3 predicts the high risk of lymphatic metastatic recurrence in pN0esophageal squamous cell carcinoma after Ivor-Lewis esophagectomy.Peerj,2015;3:e1355.
[6]Nakajima A,Ibi D,Nagai T,et al.Induction of interferon-induced transmembrane protein 3 gene expression by lipopolysaccharide in astrocytes.Eur J Pharmacol,2014,745:166-175.
[7]Mcmichael TM,Zhang L,Chemudupati M,et al.The palmitoyltransferase ZDHHC20 enhances interferon-induced transmembrane protein 3(IFITM3)palmitoylation and antiviral activity.JBiol Chem,2017,292(52):21517-21526.
[8]贾户亮,钦伦秀.肝细胞癌术后复发的预测与预防策略.中华肝脏病杂志,2016,24(5):330-334.
[9]王浩,周岩冰,牛兆建,等.早期胃癌预后及复发转移因素分析.中华普通外科杂志,2015,30(8):639-642.
[10]丛文铭.肝癌复发转移的分子机制与病理学评估策略.中华肝脏病杂志,2016,24(5):324-326.
[11]Mills TC,Rautanen A,Elliott KS,et al.IFITM3 and susceptibility to respiratory viral infections in the community.J Infet Dis,2014,209:1028-1031.
[12]Yu M,Qi W,Huang Z,et al.Expression profile and histological distribution of IFITM1 and IFITM3 during H9N2 avian influenza virus infection in BALB/c mice.Med Microbiol Immunol,2015,204(4):505-514.
[13]Bailey CC,Kondur HR,Huang I,et al.Interferon-induced transmembrane protein 3 is a type II transmembrane protein.J Biol Chem,2013,288(45):32184-32193.
[14]Xu J,Qian P,Wu Q,et al.Swine interferon-induced transmembrane protein,s IFITM3,inhibits foot-and-mouth disease virus infection in vitro and in vivo.Antiviral Res,2014,109(9):22-29.
[15]Narayana SK,Helbig KJ,Mccartney EM,et al.The interferon-induced transmembrane proteins,IFITM1,IFITM2,and I-FITM3 inhibit hepatitis C virus entry.J Biol Chem,2015,290(43):25946-25959.
[16]Eltanani MK,Jin D,Campbell FC,et al.Interferon-induced transmembrane 3 binds osteopontin in vitro:expressed in vivo I-FITM3 reduced OPN expression.Oncogene,2010,29(5):752-62.
[17]万佳,张硕,李阿茜,等.干扰素诱导的跨膜蛋白IFITM1/2/3对SFTS病毒感染的影响.中华实验和临床病毒学杂志,2016,30(3):279-282.
[18]Li D,Peng Z,Tang H,et al.KLF4-mediated negative regulation of IFITM3 expression plays a critical role in colon cancer pathogenesis.Clin Cancer Res,2011,17(11):3558-3568.
[19]Zhao B,Wang H,Zong G,et al.The role of IFITM3 in the growth and migration of human glioma cells.BMC Neurol,2013,13(1):210.
[20]Zhang D,Wang H,He H,et al.Interferon induced transmembrane protein 3 regulates the growth and invasion of human lung adenocarcinoma.Thoracic Cancer,2017,8(4):337-343.