發(fā)布時間：2018-05-27 23:34

  本文選題：胃癌 + 單核苷酸多態(tài)性��； 參考：《吉林大學(xué)》2017年碩士論文

【摘要】：胃癌是人類常見的惡性腫瘤,2012年全球約有95.2萬新發(fā)胃癌病例,72.3萬胃癌死亡病例,分別占惡性腫瘤發(fā)病率的第五位和死因第三位。盡管在發(fā)達(dá)國家的胃癌發(fā)病率和死亡率均呈現(xiàn)下降趨勢,但在我國仍然居高不下。2012年我國胃癌新發(fā)病例數(shù)為42.4萬,死亡病例數(shù)為29.8萬,均占全球的40%以上。目前隨著胃癌診斷技術(shù)的提高和術(shù)后放化療方案的進(jìn)展,胃癌患者術(shù)后生存率有所提高,但術(shù)后5年生存率僅為27.4%。研究發(fā)現(xiàn)即使處于相同的病理分期并接受相同的手術(shù)及術(shù)后治療的胃癌患者,其術(shù)后生存時間也存在差異,提示胃癌患者的預(yù)后可能與個體的遺傳背景有關(guān)。原癌基因蛋白酪氨酸磷酸酶非受體型11(PTPN11)編碼蛋白酪氨酸磷酸酶2(SHP2),在多種腫瘤組織中高表達(dá),與多種腫瘤的發(fā)生、發(fā)展和預(yù)后密切相關(guān)。目前已有研究表明PTPN11基因多態(tài)性(SNPs)與多種腫瘤的發(fā)生有關(guān),對于腫瘤預(yù)后的評估關(guān)注較少。本研究在中國胃癌高發(fā)地區(qū)的東北地區(qū)開展PTPN11基因變異與胃癌預(yù)后的研究,揭示PTPN11基因多態(tài)性作為腫瘤標(biāo)志物用于評估胃癌患者術(shù)后長期生存的可能性。目的:本研究選擇中國東北地區(qū)接受胃癌切除術(shù)的患者作為研究對象,探討中國北方漢族人群PTPN11基因單核苷酸多態(tài)性與胃癌患者術(shù)后長期生存的關(guān)系,以及PTPN11基因多態(tài)性對SHP2蛋白表達(dá)的影響,為胃癌患者實(shí)施個性化精準(zhǔn)化治療提科學(xué)的理論依據(jù)。方法:本研究選取2008年6月至2010年11月就診于吉林大學(xué)第一醫(yī)院,接受胃腫瘤切除術(shù)并經(jīng)病理學(xué)確診為胃癌的388例患者為研究對象。應(yīng)用Taq Man基因分型技術(shù)檢測PTPN11上5個SNPs位點(diǎn)(rs2301756、rs12423190、rs12229892、rs4767860和rs7958372)的基因型分布,應(yīng)用免疫組織化學(xué)技術(shù)檢測93例胃癌組織中的SHP2蛋白表達(dá)水平。Kaplan-Meier法繪制生存曲線,log-rank檢驗(yàn)比較不同基因型患者間術(shù)后生存時間的差異,應(yīng)用單因素和多因素Cox回歸模型計算風(fēng)險比(HR)及95%可信區(qū)間(95%CI)。結(jié)果:(1)本研究最終納入363例胃癌患者進(jìn)行生存分析,中位隨訪時間為60.7個月;單因素Cox回歸分析結(jié)果顯示,與PTPN11基因rs2301756 CC基因型比較,攜帶CT基因型的胃癌患者術(shù)后生存時間更短,死亡風(fēng)險更高(HR=1.78,95%CI:1.26-2.52,P=0.001),尚未發(fā)現(xiàn)其余4個位點(diǎn)的基因多態(tài)性與胃癌患者預(yù)后存在關(guān)聯(lián)。腫瘤直徑≥5cm(P0.001)、T3/T4、N2/N3、TNM分期為II/III期(P0.05),存在脈管浸潤或神經(jīng)浸潤(P0.001)的胃癌患者預(yù)后較差。(2)多因素Cox回歸分析調(diào)整混雜因素結(jié)果提示,雖然攜帶rs2301756位點(diǎn)CT基因型的胃癌患者比攜帶CC基因型胃癌患者術(shù)后死亡風(fēng)險者增加了40%(HR=1.40,95%CI:0.98-2.00),顯示了增加的趨勢,但尚未達(dá)到具有統(tǒng)計學(xué)意義的關(guān)系(P=0.064)。腫瘤TNM高分期(II/III)是影響胃癌患者預(yù)后的獨(dú)立危險因素。(3)免疫組織化學(xué)結(jié)果顯示,胃癌組織中5個SNPs的不同基因型間的SHP2蛋白表達(dá)的水平均無統(tǒng)計學(xué)差異(P0.05)。結(jié)論:PTPN11 rs2301756基因多態(tài)性可能作為胃癌患者術(shù)后長期生存預(yù)測的生物標(biāo)記物,但仍需在大樣本人群中進(jìn)行長期隨訪來驗(yàn)證。
[Abstract]:Gastric cancer is a common human malignant tumor. In 2012, there were about 95.2 million new cases of gastric cancer and 723 thousand cases of cancer death, which accounted for fifth of the incidence of malignant tumors and third of the causes of death, respectively. Although the incidence and mortality of gastric cancer in developed countries were declining, the new incidence of gastric cancer in China was still high in China for.2012 years. The number of cases was 424 thousand and the number of deaths was 298 thousand, accounting for more than 40% of the world. With the improvement of the diagnosis of gastric cancer and the progress of postoperative radiotherapy and chemotherapy, the survival rate of patients with gastric cancer was improved, but the survival rate of 5 years after the operation was only 27.4%. study found that the same pathological staging and the same operation and postoperative treatment were found. The survival time of the patients with gastric cancer is also different, suggesting that the prognosis of the patients with gastric cancer may be related to the genetic background of the individual. The proto oncogene protein tyrosine phosphatase 11 (PTPN11) encoded protein tyrosine phosphatase 2 (SHP2) is highly expressed in a variety of tumor tissues, closely related to the occurrence, development and prognosis of a variety of tumors. Research has shown that PTPN11 gene polymorphism (SNPs) is related to the occurrence of a variety of tumors and is less concerned about the prognosis of cancer. This study carried out the study of PTPN11 gene variation and prognosis of gastric cancer in the northeast region of the high incidence area of China's gastric cancer, and revealed that the polymorphism of PTPN11 gene was used as a tumor marker to evaluate the patients with gastric cancer. Objective: To investigate the possibility of long-term survival. Objective: To investigate the relationship between the single nucleotide polymorphism of PTPN11 gene and the long-term survival of the patients with gastric cancer, and the effect of the PTPN11 gene polymorphisms on the expression of SHP2 protein in the northeastern Chinese Han population, and the effect of the polymorphisms of the gene on the expression of SHP2 protein in the Chinese northeastern Han population. In this study, 388 Cases of gastric cancer were diagnosed as gastric cancer from June 2008 to November 2010, and 5 SNPs loci on PTPN11 (rs2301756, rs1242) were detected by Taq Man genotyping technique. The genotypic distribution of 3190, rs12229892, rs4767860 and rs7958372) was used to detect the survival curve of the SHP2 protein expression level in 93 cases of gastric cancer by immunohistochemistry. The difference of postoperative survival time between patients with different genotypes was compared by log-rank test, and the risk of single factor and multiple factor Cox regression model was used to calculate the risk. Results: (HR) and 95% confidence interval (95%CI). Results: (1) the survival analysis of 363 cases of gastric cancer was finally included in this study. The median follow-up time was 60.7 months. The results of single factor Cox regression analysis showed that compared with the PTPN11 gene rs2301756 CC genotype, the survival time of the patients carrying the CT genotype was shorter and the death risk was higher (HR=1.78,95). %CI:1.26-2.52, P=0.001), the gene polymorphism of the remaining 4 loci was not found to be associated with the prognosis of gastric cancer patients. The tumor diameter was more than 5cm (P0.001), T3/T4, N2/N3, TNM stage was II/III phase (P0.05), and the prognosis of gastric cancer patients with vascular infiltration or nerve infiltration (P0.001) was poor. (2) multifactor Cox regression analysis adjusted the results of confounding factors, Although the cancer patients carrying the rs2301756 locus CT genotype increased by 40% (HR=1.40,95%CI:0.98-2.00) than those with the risk of postoperative death in the patients with CC genotypic gastric cancer, the increased trend was shown, but there was no statistically significant relationship (P=0.064). The tumor TNM high stage (II/III) was an independent risk factor for the prognosis of gastric cancer patients. (3) the immunohistochemical results showed that there was no significant difference in the level of SHP2 protein expression between different genotypes of SNPs in gastric carcinoma (P0.05). Conclusion: the PTPN11 rs2301756 gene polymorphism may be used as a biomarker for long-term survival prediction of gastric cancer patients, but it still needs long-term follow-up in large sample population to verify.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R735.2

【參考文獻(xiàn)】

相關(guān)期刊論文 前9條

1 Stefano Rausei;Laura Ruspi;Federica Galli;Vincenzo Pappalardo;Giuseppe Di Rocco;Francesco Martignoni;Francesco Frattini;Francesca Rovera;Luigi Boni;Gianlorenzo Dionigi;;seventh tumor-node-metastasis staging of gastric cancer: Five-year follow-up[J];World Journal of Gastroenterology;2016年34期

2 高欣欣;王新;;影響胃癌患者預(yù)后的獨(dú)立危險因素研究進(jìn)展[J];腫瘤預(yù)防與治療;2016年02期

3 Zhi-Fang Jia;Li-Zhong Wang;Xue-Yuan Cao;Chuan Wang;Dong-Hui Cao;Xing Wu;Li-Li You;Mei-Shan Jin;Yin-Ping Wang;Bao-Sen Zhou;Jing Jiang;;CD24 genetic variants contribute to overall survival in patients with gastric cancer[J];World Journal of Gastroenterology;2016年07期

4 陳萬青;鄭榮壽;張思維;曾紅梅;左婷婷;賈漫漫;夏昌發(fā);鄒小農(nóng);赫捷;;2012年中國惡性腫瘤發(fā)病和死亡分析[J];中國腫瘤;2016年01期

5 蘇津;包娜娜;李會來;陳占國;;人類單核苷酸多態(tài)性研究進(jìn)展[J];檢驗(yàn)醫(yī)學(xué)與臨床;2014年07期

6 Jing Jiang;Mei-Shan Jin;Fei Kong;Yin-Ping Wang;Zhi-Fang Jia;Dong-Hui Cao;Hong-Xi Ma;Jian Suo;Xue-Yuan Cao;;Increased expression of tyrosine phosphatase SHP-2 in Helicobacter pylori-infected gastric cancer[J];World Journal of Gastroenterology;2013年04期

7 梁秀蘭;胡宏波;賈安平;劉振鵬;;胃癌與PTPN11基因多態(tài)性及幽門螺桿菌感染的相關(guān)性研究[J];右江民族醫(yī)學(xué)院學(xué)報;2011年03期

8 張梅玲;王建;施偉;盧凱華;束永前;劉平;;腫瘤直徑對胃癌患者預(yù)后判斷價值的分析[J];南京醫(yī)科大學(xué)學(xué)報(自然科學(xué)版);2011年02期

9 胡宏波;梁秀蘭;何建明;;PTPN11第3內(nèi)含子基因多態(tài)性及H.pylori感染與廣西柳州地區(qū)胃癌易感性研究[J];熱帶醫(yī)學(xué)雜志;2009年11期

相關(guān)碩士學(xué)位論文 前1條

1 何偉;p-SHP-2促進(jìn)胃癌患者的腫瘤浸潤和淋巴結(jié)轉(zhuǎn)移[D];安徽醫(yī)科大學(xué);2016年

，

本文編號：1944275