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The Expression Of Kiss-1 MRNA And Notch1 MRNA In Gastric Cancer Tissue And Its Clinical Significance

Posted on:2016-08-09Degree:MasterType:Thesis
Country:ChinaCandidate:Z Y DuanFull Text:PDF
GTID:2284330461969031Subject:Internal Medicine
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Objective: Gastric cancer is one of the common malignant tumor in human digestive system, and its incidence is rising all over the world. The latest data of GLOBALCAN in 2012 revealed that there were 951 thousand new cases of gastric cancer all over world, the incidence of which ranked fifth in malignant tumors around the world, with the death rates for the third and the incidence of men and women all over the word for 2-3:1. In 2014 April, New figures in 2013 of Chinese tumor registry center showed that, the incidence of gastric cancer ranked third in malignant tumor, and the mortality rate also ranked third in China, the situation of prevention and control is very serious. At present, the occurrence of gastric cancer has been confirmed to be a complex process involved with multi-gene and multi-factor, however the pathogenesis are not yet fully been known. Gastric cancer metastasis is an important cause of poor prognosis, if we can control the metastasis of gastric cancer,the survival time and prognosis of patients will be improved.Kiss-1 gene was firstly found in melanoma cell line, located in chromosome lq32-q41, with four exons encoding a hydrophilic proteins with 145 amino acids. Studies confirmed that, Kiss-1 gene acted as metastasis suppressor gene in many kinds of malignant tumor, and its down-regulation of expression is closely related to the prognosis. Notch genes were firstly discovered in fruit flies, and were cloned in 1980 for the first time, in mammals, 4 kinds of Notch receptors(Notchl-4) were found, in which Notchl has close relationship with a variety of tumor, and it plays an important role in occurrence, development and metastasis of tumors. At present, the role of the two genes in gastric cancer has not yet been elucidated.This study detected the expression of Kiss-1 m RNA and Notch1 m RNA by Rt-q PCR in tissue of gastric cancer and tissue surrounding the gastric tumor, explored the role of the two genes in the occurrence and development of gastric cancer and the relationship with the clinical, pathological and prognosis, providing new ideas for gastric cancer diagnosis and treatment.Methods:1 Tissue blocks including the tumor and the distant normal tissues were obtained from 34 patients(22males and 12 females, aged from49 to 83, with a mean age of(66.06±9.18) with gastric cancer who u-nderwent surgical resection in the First Hospital of Hebei Medical University in the period of October 2013-October 2014. No patient had r-eceived radiotherapy, chemotherapy or immunotherapy treatment before the surgical resection. The patients’ pathologic features(such as sex, age, tumor location, and Dukes’ stage, histological type,lymph nodes status, invasion depth, tumor differentiation, and distant metastasis etc.) were obtained on their informed consent.Group situation: there were 34 cases in gastric cancer group(from the surgical removal gastric cancer tissue), 34 cases in normal control group(from the normal gastricmucosa tissue more than 5 cm edge of tumor), All samples were confirmed by postoperative pathology.2 Trizol Method was employed to extract total RNA of the gastric cancer tissue and the normal tissue. Reverse transcription was conducted according to the retroviruses kit instructions of American Gene Copoeia Company. RT-q PCR technique was used to detect the expressions of Kiss-1 m RNA and Notch1 m RNA in gastric cancer tissues and normal mucosa tissues adjacent based on the instructions of the primers made by Gene Copoeia Company. The reaction conditions were as follows: 95 ℃degeneration for 10 minutes, and then the process of 95℃×10s, 60℃×30s and 72℃×10s were circulated 40 times to take the average after 3 repetitions. This study used 2-ΔCT method,in whichΔCT stood for the CT difference of target genes and CTGAPDH.3 Statistical treatment: The experiment data were analyzed by using SPSS 16.0 and presented by medians(quartile range). The paired samples and independent samples between groups were tested by Wilcoxon and Mann-Whitney U respectively,and the difference(P<0.05)was statistically significant.Results:1 The expression of Kiss- 1 m RNA in gastric cancer group decreased significantly compared with normal control group, the difference between the two groups have statistical significance(P<0.05).2 The expression of Kiss-1 m RNA in the gastric cancer group with lymph node metastasis, distant metastasis, and TNM stage III-IV is significantly lower than the expression in the no lymph node metastasis group, no distant metastasis group and I- II group, the difference between the two groups have statistical significance(P<0.05).3 The expression of Notch1 m RNA in gastric cancer group increased significantly compared with normal control group, the difference between the two groups have statistical significance(P<0.05).4 The expression of Notch 1 m RNA in the gastric cancer group with lymph node metastasis and TNM stage III-IV is significantly higher than the expression in the no lymph node metastasis group and I-II group, the difference between the two groups have statistical significance(P < 0.05).5 The expression of Notch1 m RNA in Poorly differentiated gastric cancer group is significantly higher than the expression in high differentiated gastric cancer group(P< 0.05).6 The expression of Kiss-1 m RNA and Notch1 m RNA have no obvious correlation with sex, age, pathological type of patients, the difference between the two groups have no statistical significance(P> 0.05).Conclusions:1 Significantly down regulated the expression of Kiss-1 m RNA in gastric cancer tissues compared with normal tissues adjacent to carcinoma, suggesting that it may play in the pathogenesis of gastric cancer tumor suppressor role.2 Expression of gastric cancer Kiss-1 m RNA is closely related with gastric cancer staging, lymph node metastasis, suggests that it may affect the prognosis of gastric cancer by suppression of metastasis to the gastric cancer.3 The expression of Notch1 m RNA in gastric cancer tissue than in adjacent normal tissue was significantly up-regulated,suggesting that it may play in the pathogenesis of gastric cancer in the cancer promoting effects.4 The expression of Notch1 m RNA is closely related with gastric cancer staging, lymph node metastasis and differentiation degree, high expression further suggest that Notch1 m RNA promoted the progression of gastric cancer, has the potential to become a novel tumor marker in the early diagnosis of gastric cancer for early diagnosis of gastric cancer.
Keywords/Search Tags:Gastric cancer, Kiss-1 mRNA, Notch1 mRNA, Metastasis
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