PTPRS在食管腺癌中的表达水平及临床意义
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摘要
目的探讨蛋白酪氨酸磷酸酶受体S(PTPRS)在食管腺癌组织中的表达及临床意义。方法应用组织芯片技术和免疫组织化学法检测71例食管腺癌患者的癌组织、癌旁组织及食管正常黏膜中PTPRS蛋白的表达情况,分析PTPRS蛋白与食管腺癌患者临床病理特征和预后的关系。结果 PTPRS蛋白在食管腺癌组织中表达量低于食管正常黏膜组织(P<0.05)。不同临床分期、浸润深度、淋巴结转移状态、分化程度、神经受侵及脉管瘤栓的食管腺癌患者的PTPRS蛋白表达水平比较,差异有统计学意义(P<0.05)。Kaplan-Meier生存分析显示,PTPRS低表达患者生存率低于高表达患者(P<0.05);多因素Cox回归分析显示,PTPRS为食管腺癌患者预后不良的独立危险因素[H^lR=2.265,(95%CI:1.050,4.887),P=0.037]。结论 PTPRS蛋白低表达与食管腺癌患者的复发和预后密切相关。PTPRS可能是潜在的抑癌基因,在食管癌的发生、发展中发挥重要的调控作用。
Objective To study the clinical significance and expression level of protein tyrosine phosphatase receptor S(PTPRS) in human esophageal adenocarcinoma tissues. Methods Clinicopathological and prognostic roles of PTPRS in 71 cases of esophageal adenocarcinoma were investigated. Paraffin embedded tissue with immunohistochemistry methods and tissue microarrays(TMAs) were adopted to exam PTPRS expression in esophageal adenocarcinoma, paired normal esophageal mucosa and adjacent tissues. Results PTPRS was significantly down-regulated in esophageal adenocarcinoma compared to normal tissues(P < 0.05). Statistical analysis revealed that PTPRS expression was significantly associated with TNM stage, invasion depth, local lymph node metastasis, tumor differentiation, nerves invaded and vascular invasion(P < 0.05). Furthermore,Kaplan-Meier survival analysis revealed that low expression of PTPRS significantly was correlated with shorter overall survival of esophageal adenocarcinoma patients(P < 0.05). Cox regression analysis confirmed PTPRS expression as an independent predictor of the overall survival of ESCC patients [Hl^R=2.265,(95% CI: 1.050, 4.887),P = 0.037]. Conclusions PTPRS may be a new potential tumor suppressor gene, plays an important role in tumor development and may serve as a reliable indicator for prognostic prediction in esophageal adenocarcinoma patients.
Objective To study the clinical significance and expression level of protein tyrosine phosphatase receptor S(PTPRS) in human esophageal adenocarcinoma tissues. Methods Clinicopathological and prognostic roles of PTPRS in 71 cases of esophageal adenocarcinoma were investigated. Paraffin embedded tissue with immunohistochemistry methods and tissue microarrays(TMAs) were adopted to exam PTPRS expression in esophageal adenocarcinoma, paired normal esophageal mucosa and adjacent tissues. Results PTPRS was significantly down-regulated in esophageal adenocarcinoma compared to normal tissues(P < 0.05). Statistical analysis revealed that PTPRS expression was significantly associated with TNM stage, invasion depth, local lymph node metastasis, tumor differentiation, nerves invaded and vascular invasion(P < 0.05). Furthermore,Kaplan-Meier survival analysis revealed that low expression of PTPRS significantly was correlated with shorter overall survival of esophageal adenocarcinoma patients(P < 0.05). Cox regression analysis confirmed PTPRS expression as an independent predictor of the overall survival of ESCC patients [Hl^R=2.265,(95% CI: 1.050, 4.887),P = 0.037]. Conclusions PTPRS may be a new potential tumor suppressor gene, plays an important role in tumor development and may serve as a reliable indicator for prognostic prediction in esophageal adenocarcinoma patients.
引文
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[5]STEWART K, UETANI N, HENDRIKS W, et al. Inactivation of LAR family phosphatase genes Ptprs and Ptprf causes craniofacial malformations resembling pierre-robin sequence[J]. Development,2013, 140(16):3413-3422.
[6]SOULIèRES D,HIRSCH F R,SHEPHERD F A, et al. PTPRF expression as a potential prognostic/predictive marker for treatment with erlotinib in non-small-cell lung cancer[J]. J Thorac Oncol,2015, 10(9):1364-1369.
[7]ACUN T, DEMIR K, OZTAS E, et al. PTPRD is homozygously deleted and epigenetically downregulated in human hepatocellular carcinomas[J]. OMICS, 2015, 19(4):220-229.
[8]WILJAN H, ANNIKA B, WILLIAM L, et al. Proteinaceous regulators and inhibitors of protein tyrosine phosphatases[J].Molecules, 2018, 23(2):1-22.
[9]KIM M, MORALES L D, JANG I S, et al. Protein tyrosine phosphatases as potential regulators of STAT3 signaling[J]. Int J Mol Sci, 2018, 19(9):1-19.
[10]BUNIN A,SISIRAK V,GHOSH H S, et al. Protein tyrosine phosphatase PTPRS is an inhibitory receptor on human and murine plasmacytoid dendritic cells[J]. Immunity, 2015, 43(2):277-288.
[11]MORRIS L G, TAYLOR B S, BIVONA T G, et al. Genomic dissection of the epidermal growth factor receptor(EGFR)/PI3K pathway reveals frequent deletion of the EGFR phosphatase PTPRS in head and neck cancers[J]. Proc Natl Acad Sci USA,2011, 108(47):19024-19029.
[12]GAO Q, ZHAO Y J, WANG X Y, et al. Activating mutations in PTPN3 promote cholangiocarcinoma cell proliferation and migration and are associated with tumor recurrence in patients[J].Gastroenterology, 2014, 146(5):1397-1407.
[13]KUDRYAVTSEVA A V, LIPATOVA A V, ZARETSKY A R, et al. Important molecular genetic markers of colorectal cancer[J].Oncotarget, 2016, 7(33):53959-53983.
[14]WALIA V, PRICKETT T D, KIM J S, et al. Mutational and functional analysis of the tumor-suppressor PTPRD in human melanoma[J]. Hum Mutat, 2014, 35(11):1301-1310.
[15]DAVIS T B, YANG M, SCHELL M J, et al. PTPRS regulates colorectal cancer RAS pathway activity by inactivating erk and preventing its nuclear translocation[J]. Sci Rep, 2018, 8(1):92-96.
[2]WANG Z C, GAO Q, SHI J Y, et al. Protein tyrosine phosphatase receptor S acts as a metastatic suppressor in hepatocellular carcinoma by control of epithermal growth factor receptor-induced epithelial-mesenchymal transition[J]. Hepatology, 2015, 62(4):1201-1214.
[3]MORRIS L G, CHAN T A. Resistance to EGFR inhibitors:molecular determinants and the enigma of head and neck cancer[J].Oncotarget, 2011, 2(12):894-895.
[4]李浩淼,孙海波,郑燕,等. AJCC/UICC第八版食管及食管胃交界部癌TNM分期解读及中文版主要内容[J].中国胸心血管外科临床杂志, 2017, 24(2):87-92.
[5]STEWART K, UETANI N, HENDRIKS W, et al. Inactivation of LAR family phosphatase genes Ptprs and Ptprf causes craniofacial malformations resembling pierre-robin sequence[J]. Development,2013, 140(16):3413-3422.
[6]SOULIèRES D,HIRSCH F R,SHEPHERD F A, et al. PTPRF expression as a potential prognostic/predictive marker for treatment with erlotinib in non-small-cell lung cancer[J]. J Thorac Oncol,2015, 10(9):1364-1369.
[7]ACUN T, DEMIR K, OZTAS E, et al. PTPRD is homozygously deleted and epigenetically downregulated in human hepatocellular carcinomas[J]. OMICS, 2015, 19(4):220-229.
[8]WILJAN H, ANNIKA B, WILLIAM L, et al. Proteinaceous regulators and inhibitors of protein tyrosine phosphatases[J].Molecules, 2018, 23(2):1-22.
[9]KIM M, MORALES L D, JANG I S, et al. Protein tyrosine phosphatases as potential regulators of STAT3 signaling[J]. Int J Mol Sci, 2018, 19(9):1-19.
[10]BUNIN A,SISIRAK V,GHOSH H S, et al. Protein tyrosine phosphatase PTPRS is an inhibitory receptor on human and murine plasmacytoid dendritic cells[J]. Immunity, 2015, 43(2):277-288.
[11]MORRIS L G, TAYLOR B S, BIVONA T G, et al. Genomic dissection of the epidermal growth factor receptor(EGFR)/PI3K pathway reveals frequent deletion of the EGFR phosphatase PTPRS in head and neck cancers[J]. Proc Natl Acad Sci USA,2011, 108(47):19024-19029.
[12]GAO Q, ZHAO Y J, WANG X Y, et al. Activating mutations in PTPN3 promote cholangiocarcinoma cell proliferation and migration and are associated with tumor recurrence in patients[J].Gastroenterology, 2014, 146(5):1397-1407.
[13]KUDRYAVTSEVA A V, LIPATOVA A V, ZARETSKY A R, et al. Important molecular genetic markers of colorectal cancer[J].Oncotarget, 2016, 7(33):53959-53983.
[14]WALIA V, PRICKETT T D, KIM J S, et al. Mutational and functional analysis of the tumor-suppressor PTPRD in human melanoma[J]. Hum Mutat, 2014, 35(11):1301-1310.
[15]DAVIS T B, YANG M, SCHELL M J, et al. PTPRS regulates colorectal cancer RAS pathway activity by inactivating erk and preventing its nuclear translocation[J]. Sci Rep, 2018, 8(1):92-96.