PTPN12在食管鳞状细胞癌中的表达及其临床意义的研究

发布时间：2018-04-24 20:43

本文选题：PTPN12 + 食管鳞状细胞癌　；参考：《河北医科大学》2017年硕士论文

【摘要】：目的:对于中国人群中非受体型蛋白酪氨酸磷酸酶12(Protein Tyrosine Phosphatase,Non-Receptor Type 12,PTPN12)与食管癌的相关报道非常少。本实验探讨PTPN12蛋白在食管鳞状细胞癌组织、癌旁组织及正常食管粘膜组织中的表达情况,并分析其表达水平与食管鳞状细胞癌各项临床病理因素的关系,同时结合临床随访资料研究PTPN12的表达水平对患者术后生存与复发的影响。方法:1 PTPN12在不同食管癌组织、癌旁组织及正常组织中的表达。收集2004年7月-2016年10月间于河北医科大学第四医院行食管鳞状细胞癌根治术的患者200例以及41例癌旁组织和41例正常食管粘膜组织,应用组织芯片技术和免疫组织化学的方法检测其PTPN12蛋白的表达情况。2 PTPN12表达与临床病理特征的关系。整理200例食管癌患者的发病年龄、性别、TNM分期、有无淋巴结转移等临床病理资料,分析PTPN12蛋白的表达与食管鳞状细胞癌临床病理特征的关系;3 PTPN12表达与患者预后的关系。分析PTPN12蛋白的表达对食管鳞状细胞癌术后患者生存、复发的影响。4统计方法对41例癌组织、癌旁组织及正常组织中PTPN12蛋白的表达量比较运用X2检验,PTPN12蛋白的表达与食管鳞状细胞癌临床病理特征的关系运用X2检验,采用Kaplan-Meier分析和Cox回归多因素分析来分析PTPN12蛋白的表达对食管鳞状细胞癌术后患者生存及复发的影响。结果:1免疫组化结果显示:PTPN12蛋白表达量在癌组织中显著低于正常食管粘膜组织(P=0.001);在癌组织与癌旁组织中的表达无明显差异(P=0.054);在癌旁组织中与正常食管粘膜组织中无明显差异(P=0.091)。2 PTPN12蛋白在肿瘤组织中的表达与肿瘤的TNM分期(P=0.018)、侵犯深度(P=0.027)、淋巴结转移情况(P=0.034)、肿瘤大小(P=0.035)、饮酒史(P=0.020)具有一定的相关性,与年龄、性别、吸烟史、家族史无显著相关性。3 Kaplan-Meier分析即单因素分析显示,癌组织中PTPN12低表达、有淋巴结转移、肿瘤分化程度差、TNM分期晚、肿瘤侵犯深、术后未行辅助化疗是影响ESCC病人术后总体生存的高危因素。食管鳞癌组织中PTPN12蛋白高表达组1年、3年、5年生存率及总生存率均显著高于低表达组(P=0.0060.05);PTPN12蛋白低表达、有淋巴结转移、肿瘤分化差、TNM分期晚、肿瘤侵犯深、术后未行辅助化疗是影响ESCC术后病人复发的危险因素。PTPN12蛋白高表达组1年、3年、5年的复发率及总复发率显著低于低表达组(P=0.0030.05)。4多因素分析显示患者食管鳞癌组织中PTPN12低表达(HR=1.478,95%CI可信区间:0.975-2.241,P=0.048)、有淋巴结转移(HR=0.483,95%CI可信区间:0.274-0.852,P=0.012)、肿瘤分化程度差(HR=0.568,95%CI可信区间:0.349-0.924,P=0.023)、术后未行辅助化疗(HR=2.077,95%CI可信区间:1.420-3.037,P=0.000)是影响ESCC患者术后生存的高危因素;食管鳞癌组织中PTPN12低表达(HR=1.691,95%CI可信区间:1.018-2.808,P=0.043)、有淋巴结转移(HR=0.315395%CI可信区间:0.159-0.615,P=0.001)、术后未行辅助化疗(HR=1.578,95%CI可信区间:1.009-2.469,P=0.046)是影响食管鳞癌患者术后复发的危险因素。结论:1 PTPN12蛋白在食管鳞状细胞癌中表达明显低于正常食管粘膜组织,其在癌旁组织及正常食管粘膜组织中的表达无明显差异。此结果提示PTPN12在食管鳞癌中处于低表达状态,换一角度表明PTPN12可能为食管鳞癌中的抑癌基因。2 PTPN12蛋白在食管鳞状细胞癌组织中的表达水平与肿瘤的淋巴结转移、侵犯深度、TNM分期、肿瘤大小、饮酒史具有相关性。这些结果提示PTPN12蛋白可能参与食管鳞状细胞癌的发生、侵袭和转移。3 PTPN12蛋白的低表达是影响患者术后生存、复发的独立危险因素,高表达组其生存率高于低表达组,复发率低于低表达组。此结果提示,PTPN12蛋白在食管鳞状细胞癌中高表达可能在抑制食管鳞癌的转移、复发中发挥重要作用。因此,PTPN12有可能作为预测食管鳞状细胞癌患者预后的一个指标,也为食管鳞状细胞癌的分子靶向治疗提供一些新的思路。4 术后未行完整化疗及淋巴结转移是影响食管鳞癌患者术后生存及复发的独立危险因素。
[Abstract]:Objective: the reports of non receptor type protein tyrosine phosphatase 12 (Protein Tyrosine Phosphatase, Non-Receptor Type 12, PTPN12) with esophageal cancer are very few in Chinese population. The expression of PTPN12 protein in squamous cell carcinoma of the esophagus, para cancerous tissue and normal canalical mucosa was investigated and the expression of water was analyzed. The relationship between the clinicopathological factors of squamous cell carcinoma of the esophagus and the effect of the expression level of PTPN12 on postoperative survival and recurrence of the patients. Methods: 1 PTPN12 expression in different esophageal cancer tissues, para cancer tissues and normal tissues. Collected in July 2004, -2016, October, at Hebei Medical University, Fourth 200 patients with esophageal squamous cell carcinoma radical resection, 41 cases of para cancerous tissue and 41 normal esophageal mucosa tissues, the expression of PTPN12 protein was detected by tissue chip technique and immunohistochemistry. The relationship between the expression of.2 PTPN12 and the clinicopathological features of the esophageal squamous cell carcinoma was detected. The onset age, sex, and TNM of the patients with esophageal cancer were sorted. The relationship between the expression of PTPN12 protein and the clinicopathological features of squamous cell carcinoma of the esophagus, the relationship between the expression of PTPN12 protein and the clinicopathological features of esophageal squamous cell carcinoma, the relationship between the expression of PTPN12 and the prognosis of the patients. Analysis of the effect of the expression of PTPN12 protein on the survival and recurrence of postoperative patients with squamous cell carcinoma of the esophagus by.4 statistics method for 41 cases of cancer tissue and para cancerous tissue The expression of PTPN12 protein in normal tissues was compared with X2 test. The relationship between the expression of PTPN12 protein and the clinicopathological features of esophageal squamous cell carcinoma was examined by X2 test. The effects of the expression of PTPN12 protein on the survival and recurrence of postoperative patients with squamous cell carcinoma of the esophagus were analyzed by Kaplan-Meier analysis and multivariate analysis of Cox regression. 1 the results of immunohistochemistry showed that the expression of PTPN12 protein was significantly lower than that in normal esophageal mucosa (P=0.001), and there was no significant difference between the cancer tissue and the para cancer tissue (P=0.054), and there was no significant difference between the para cancer tissue and the normal esophageal mucosa (P= 0.091) the expression of.2 PTPN12 protein in the tumor tissues and the T of the tumor. NM staging (P=0.018), invasion depth (P=0.027), lymph node metastasis (P=0.034), tumor size (P=0.035) and drinking history (P=0.020) have a certain correlation. There is no significant correlation with age, sex, smoking history and family history. The single factor analysis of.3 Kaplan-Meier analysis shows that the low expression of PTPN12 in the cancer tissue, lymph node metastasis, and tumor differentiation process The TNM staging was late, the tumor invasion was deep and the postoperative adjuvant chemotherapy was a high risk factor for the overall survival of ESCC patients. The high expression group of PTPN12 protein in the tissue of esophageal squamous cell carcinoma was 1 years and 3 years, the 5 year survival rate and total survival rate were significantly higher than those of the low expression group (P=0.0060.05), and the low expression of PTPN12 protein, lymph node metastasis, the poor differentiation of tumor, TNM Late stage, deep tumor invasion and non adjuvant chemotherapy after operation were the risk factors for the recurrence of ESCC after ESCC,.PTPN12 protein high expression group was 1 years, 3 years, 5 year recurrence rate and total recurrence rate were significantly lower than that of low expression group (P=0.0030.05).4 multifactor analysis showed the low expression of PTPN12 in the patients with esophageal squamous cell carcinoma (HR=1.478,95%CI confidence interval: 0.975-2 .241, P=0.048), there are lymph node metastases (HR=0.483,95%CI confidence interval: 0.274-0.852, P=0.012), poor differentiation of tumor (HR=0.568,95%CI confidence interval: 0.349-0.924, P=0.023). Postoperative adjuvant chemotherapy (HR=2.077,95%CI confidence interval: 1.420-3.037, P=0.000) is a high risk factor for postoperative survival of the patients; esophageal squamous cell carcinoma tissue Low expression (HR=1.691,95%CI confidence interval: 1.018-2.808, P=0.043), lymph node metastases (HR=0.315395%CI confidence interval: 0.159-0.615, P=0.001). Postoperative adjuvant chemotherapy (HR=1.578,95%CI confidence interval: 1.009-2.469, P=0.046) is a risk factor affecting postoperative recurrence of esophageal squamous cell carcinoma. Conclusion: 1 PTPN12 protein in squamous cell carcinoma of the esophagus The expression of PTPN12 is obviously lower than normal esophageal mucosa, and there is no significant difference in the expression of the para cancer tissue and normal esophageal mucosa. This results suggest that the expression of PTPN12 in the squamous cell carcinoma of the esophagus is low, and that PTPN12 may be the table of the tumor suppressor gene.2 PTPN12 protein in the squamous cell carcinoma of the esophagus. The levels are associated with lymph node metastasis, invasion depth, TNM staging, tumor size, and drinking history. These results suggest that PTPN12 protein may be involved in the occurrence of squamous cell carcinoma of the esophagus, and the low expression of the invasion and metastasis of.3 PTPN12 protein is an independent risk factor for the survival and recurrence of the patients. The high expression rate of the high expression group is higher than that of the high expression group. The results suggest that the high expression of PTPN12 protein in esophageal squamous cell carcinoma may play an important role in inhibiting the metastasis and recurrence of esophageal squamous cell carcinoma. Therefore, PTPN12 may be an indicator for predicting the prognosis of squamous cell carcinoma of the esophagus and the molecular targeting of esophageal squamous cell carcinoma. Treatment provides some new ideas..4 after surgery without complete chemotherapy and lymph node metastasis is an independent risk factor for postoperative survival and recurrence of esophageal squamous cell carcinoma.

【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R735.1

【参考文献】