本文選題：PTPN12 + 食管鱗狀細(xì)胞癌　； 參考：《河北醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的:對(duì)于中國人群中非受體型蛋白酪氨酸磷酸酶12(Protein Tyrosine Phosphatase,Non-Receptor Type 12,PTPN12)與食管癌的相關(guān)報(bào)道非常少。本實(shí)驗(yàn)探討PTPN12蛋白在食管鱗狀細(xì)胞癌組織、癌旁組織及正常食管粘膜組織中的表達(dá)情況,并分析其表達(dá)水平與食管鱗狀細(xì)胞癌各項(xiàng)臨床病理因素的關(guān)系,同時(shí)結(jié)合臨床隨訪資料研究PTPN12的表達(dá)水平對(duì)患者術(shù)后生存與復(fù)發(fā)的影響。方法:1 PTPN12在不同食管癌組織、癌旁組織及正常組織中的表達(dá)。收集2004年7月-2016年10月間于河北醫(yī)科大學(xué)第四醫(yī)院行食管鱗狀細(xì)胞癌根治術(shù)的患者200例以及41例癌旁組織和41例正常食管粘膜組織,應(yīng)用組織芯片技術(shù)和免疫組織化學(xué)的方法檢測其PTPN12蛋白的表達(dá)情況。2 PTPN12表達(dá)與臨床病理特征的關(guān)系。整理200例食管癌患者的發(fā)病年齡、性別、TNM分期、有無淋巴結(jié)轉(zhuǎn)移等臨床病理資料,分析PTPN12蛋白的表達(dá)與食管鱗狀細(xì)胞癌臨床病理特征的關(guān)系;3 PTPN12表達(dá)與患者預(yù)后的關(guān)系。分析PTPN12蛋白的表達(dá)對(duì)食管鱗狀細(xì)胞癌術(shù)后患者生存、復(fù)發(fā)的影響。4統(tǒng)計(jì)方法對(duì)41例癌組織、癌旁組織及正常組織中PTPN12蛋白的表達(dá)量比較運(yùn)用X2檢驗(yàn),PTPN12蛋白的表達(dá)與食管鱗狀細(xì)胞癌臨床病理特征的關(guān)系運(yùn)用X2檢驗(yàn),采用Kaplan-Meier分析和Cox回歸多因素分析來分析PTPN12蛋白的表達(dá)對(duì)食管鱗狀細(xì)胞癌術(shù)后患者生存及復(fù)發(fā)的影響。結(jié)果:1免疫組化結(jié)果顯示:PTPN12蛋白表達(dá)量在癌組織中顯著低于正常食管粘膜組織(P=0.001);在癌組織與癌旁組織中的表達(dá)無明顯差異(P=0.054);在癌旁組織中與正常食管粘膜組織中無明顯差異(P=0.091)。2 PTPN12蛋白在腫瘤組織中的表達(dá)與腫瘤的TNM分期(P=0.018)、侵犯深度(P=0.027)、淋巴結(jié)轉(zhuǎn)移情況(P=0.034)、腫瘤大小(P=0.035)、飲酒史(P=0.020)具有一定的相關(guān)性,與年齡、性別、吸煙史、家族史無顯著相關(guān)性。3 Kaplan-Meier分析即單因素分析顯示,癌組織中PTPN12低表達(dá)、有淋巴結(jié)轉(zhuǎn)移、腫瘤分化程度差、TNM分期晚、腫瘤侵犯深、術(shù)后未行輔助化療是影響ESCC病人術(shù)后總體生存的高危因素。食管鱗癌組織中PTPN12蛋白高表達(dá)組1年、3年、5年生存率及總生存率均顯著高于低表達(dá)組(P=0.0060.05);PTPN12蛋白低表達(dá)、有淋巴結(jié)轉(zhuǎn)移、腫瘤分化差、TNM分期晚、腫瘤侵犯深、術(shù)后未行輔助化療是影響ESCC術(shù)后病人復(fù)發(fā)的危險(xiǎn)因素。PTPN12蛋白高表達(dá)組1年、3年、5年的復(fù)發(fā)率及總復(fù)發(fā)率顯著低于低表達(dá)組(P=0.0030.05)。4多因素分析顯示患者食管鱗癌組織中PTPN12低表達(dá)(HR=1.478,95%CI可信區(qū)間:0.975-2.241,P=0.048)、有淋巴結(jié)轉(zhuǎn)移(HR=0.483,95%CI可信區(qū)間:0.274-0.852,P=0.012)、腫瘤分化程度差(HR=0.568,95%CI可信區(qū)間:0.349-0.924,P=0.023)、術(shù)后未行輔助化療(HR=2.077,95%CI可信區(qū)間:1.420-3.037,P=0.000)是影響ESCC患者術(shù)后生存的高危因素;食管鱗癌組織中PTPN12低表達(dá)(HR=1.691,95%CI可信區(qū)間:1.018-2.808,P=0.043)、有淋巴結(jié)轉(zhuǎn)移(HR=0.315395%CI可信區(qū)間:0.159-0.615,P=0.001)、術(shù)后未行輔助化療(HR=1.578,95%CI可信區(qū)間:1.009-2.469,P=0.046)是影響食管鱗癌患者術(shù)后復(fù)發(fā)的危險(xiǎn)因素。結(jié)論:1 PTPN12蛋白在食管鱗狀細(xì)胞癌中表達(dá)明顯低于正常食管粘膜組織,其在癌旁組織及正常食管粘膜組織中的表達(dá)無明顯差異。此結(jié)果提示PTPN12在食管鱗癌中處于低表達(dá)狀態(tài),換一角度表明PTPN12可能為食管鱗癌中的抑癌基因。2 PTPN12蛋白在食管鱗狀細(xì)胞癌組織中的表達(dá)水平與腫瘤的淋巴結(jié)轉(zhuǎn)移、侵犯深度、TNM分期、腫瘤大小、飲酒史具有相關(guān)性。這些結(jié)果提示PTPN12蛋白可能參與食管鱗狀細(xì)胞癌的發(fā)生、侵襲和轉(zhuǎn)移。3 PTPN12蛋白的低表達(dá)是影響患者術(shù)后生存、復(fù)發(fā)的獨(dú)立危險(xiǎn)因素,高表達(dá)組其生存率高于低表達(dá)組,復(fù)發(fā)率低于低表達(dá)組。此結(jié)果提示,PTPN12蛋白在食管鱗狀細(xì)胞癌中高表達(dá)可能在抑制食管鱗癌的轉(zhuǎn)移、復(fù)發(fā)中發(fā)揮重要作用。因此,PTPN12有可能作為預(yù)測食管鱗狀細(xì)胞癌患者預(yù)后的一個(gè)指標(biāo),也為食管鱗狀細(xì)胞癌的分子靶向治療提供一些新的思路。4 術(shù)后未行完整化療及淋巴結(jié)轉(zhuǎn)移是影響食管鱗癌患者術(shù)后生存及復(fù)發(fā)的獨(dú)立危險(xiǎn)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.

【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R735.1

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本文編號(hào)：1798202