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Expression And Clinical Significance Of PTK7 In Gastric Adenocarcinoma

Posted on:2016-05-26Degree:MasterType:Thesis
Country:ChinaCandidate:Z S XieFull Text:PDF
GTID:2284330461950779Subject:Surgery
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Background and ObjectiveGastric cancer(GC) is one of the most common cancers in humans,90% of them are gastric adenocarcinoma(GAC).While,GC is characterized by invasion and metastasis, which are major causes contributing to the lethality of this disease. According to the World Health Organization, GC is the fifth most common malignancy worldwide, and with an extremely poor prognosis, is the second leading cause of cancer death worldwide for time of the diagnosis are late.Because most of them are mistaken for chronic gastritis.It is the fact that GC is very common in Asian countries,especially in Japan,which in southeast Asia,have a higher morbidity and mortality of GC.The incidence of GC is very high in Our country,the east of China,the morbidity and mortality of GC is higher than the northwest, the incidence of GC in China is about 22.7/100 thousand. patient survival and outcomes remains poor inspite of Operation and chemotherapy regimens have quite a specification in GC.Most probably the poor outcome had a lot relation with patients diagnosis in advanced stages.GC is due to the occurrence and development of a variety of internal and external factors work together, but we know very little about the molecular biology behavior, in view of the GC molecular mechanism of the occurrence and development of the meaning of the research is very important.The protein tyrosine kinase 7(PTK7),is one of recepter protein tyrosine kinase(RTK) lack of catalytic activity, was first discovered as a gene overexpressed in colon cancer cell lines,so is called colon carcinoma kinase 4(CCK4), It is a new member of receptor protein tyrosine kinase family. The PTK7 gene organized into 20 exons,is a receptor tyrosine kinase like molecule containing an extracellular domain with seven immunoglobulin-like loops, a transmembrane domain.In recent study,PTK7 is a common receptor with multi-fuction of PTK7/Otk, The expression of PTK7 is up-regulation in various cancers of human,including acute myeloid leukemia,colon cancer,lung cancer,esophageal squamous cell carcinoma,and also have abnormal expression in hepatocellular carcinoma, head and neck squamous cell carcinomas, and ovarian epithelial carcinoma.The research has shown that PTK7 have inseparable relationship with the occurrence of tumors.So far, the expression of PTK7 in GAC reported in domestic is poor.In our study, immunohistochemical staining(Envision method) to detect the differences expression of PTK7 in GAC tissues with normal gastric mucosa tissues,and its clinical pathological characteristics. Kaplan-Meier survival function was used to analyze the prognosis. To compare 3-year survival rate, recurrence rate and 5-year survival rate of negative and positive expression of PTK7 in gastric adenocarcinoma patients. To explor the role of PTK7 played in the metastasis and invasion of GAC. Material and method 1 Specimen collection and research objectsThe study cohort consisted of 210 GAC tissue samples and 30 normal gastric mucosa tissues obtained from patients who underwent surgery from the years January 2011 to December 2011 in the First Affiliated Hospital of Zhengzhou University of Gastrointestinal Surgery,then followed by gastrectomy with D2/D3 lymphade-nectomy.and GAC patients were not conducted other treatments as chemotherapy and radiation therapy, integrative therapy before the surgery, and postoperative examination confirmed GAC or normal gastric mucosa.All of the GAC patients informed consents, and approved by the ethics committee and reported.Clean up the blood and resection specimens within 30 min, to avoid rot necrotic tissue, the tissue size is about 1.0 cm*1.0 cm * 1.0 cm, which is in the center of the cancer, normal gastric mucosa tissues taken from gastric stump or tumor edge out 8 cm outside the organization,Specimens fixed by the formalin of 10% after collection, normal gastric mucosa tissues and GAC organize routine paraffin embedding and slice,then stored in the refrigerator.censored criteria:Once received preoperative interventional surgery, radiation and chemotherapy, and other treatment, or has a history of digestive system malignant tumor,all patients in this study were followed up for 36 months or more, a complete clinical data and medical records get from the first affiliated hospital of Zhengzhou university. 2 research methods2.1 Immunohistochemical staining(Envision method) and RT-PCR was used to detect the expression of PTK7 in GAC tissues and normal gastric mucosa tissues2.2 Analysis the expression of PTK7 in GAC with clinical pathological characteristics,such as gender,age,location,size of the tumor,Lauren classification, differentiation,invasion depth and distant metastasis2.3 Analysis the differences expression of PTK7 in GAC tissues with normal gastric mucosa tissues2.4 analyze the 3 years survival rates, recurrence rates and 1 years survival rates of negative and positive expression of PTK7 in gastric adenocarcinoma patients. 3 Statistical processingSPSS17.0 software was used for data analysis.The categorical variables were compared by chi-square test. The Kaplan–Meier method(K-M) was used to calculate the survival distribution.In all of the statistical analyses, P<0.05 was considered significant. Results1.In GAC tissues,the positive expression of PTK7 was 87.14%(183/210),the positive expression was 22.86%(27/183),In normal gastric mucosa tissues,the positive expression of PTK7 was 66.67%(20/30),the positive expression was 33.33%(10/30),the differences was considered significant(P=0.012)2.In GAC tissues,the expression of PTK7 has no differences in gender(χ2 =0.437,P=0.508),age(t=1.55,P=0.122),location(χ2 =0.255,P=0.880),size of the tumor(χ2 =0.004,P=0.947),but relate to Lauren classification(χ2 =6.640,P=0.011),differentiation(χ2 =6.468,P=0.039),invasion depth(χ2 =5.007,P=0.025)and distant metastasis(P=0.034).3.In GAC tissues, positive expression of PTK7 the 3 years survival rates was 39.89%(73/183),in negative expression of PTK7 was 62.96%(17/27),the differences was considered significant(χ2 =5.114,P=0.024).positive expression of PTK7 the 1 years survival rates was 16.39%(30/183),in negative expression of PTK7 was33.33%(9/27),the differences was considered significant(χ2 =4.465, P=0.035),the recurrence rates of them are 34.43%(63/183) and14.81%(9/27),the differences was considered significant(χ2 =4.165,P=0.041). Conclusions1.the expression of PTK7 in GAC is higher than normal gastric mucosa tissues,the high expression of PTK7 related to clinical pathological characteristics2.PTK7 may be a useful biomarker to predict a the prognosis for patients with gastric adenocarcinoma3.PTK7 might be a potential therapeutic target molecule or marker.
Keywords/Search Tags:gastric adenocarcinoma, protein tyrosine kinase 7, immunohistochemical reverse, transcriptase polymerase chain reaction, survival rates
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