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Expression Of PI3K And LRIG1 Genes In Esophageal Squamous Cell Carcinoma As Used To Observe Of Chemoradiotherapy

Posted on:2015-12-12Degree:MasterType:Thesis
Country:ChinaCandidate:H LiuFull Text:PDF
GTID:2284330461498707Subject:Oncology
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Introduction Eesophagus cancer refers to the swallow esophagogastric junction between the esophagus epithelium of primary malignancies. The incidence of esophageal cancer in the world ranked eighth among all cancers, but the cause of death in cancer cases in the first six common reasons, suggesting that not only is the common malignant esophageal cancer, but also on a very human-caused big health hazard. China is a high incidence of esophageal cancer, esophageal cancer deaths accounted for 21.8% of cancer deaths,ranked second in the country. Because early diagnosis is difficult, resulting in the majority of patients already advanced at the time of clinical treatment, the prognosis is poor. Constant depth of esophageal cancer incidence and prognosis will help to improve the diagnosis and treatment of esophageal cancer.Phosphatidylinositol-3-kinase signaling pathway is closely related to the development of many human tumors. According PI3 K structures, substrates, activation mechanisms, distribution and function can be divided into three categories: I, II, III sub-types. According to the different types coupled receptor type I PI3 K is further divided into: IA type and IIB type, the former coupled tyrosine kinase growth factor receptor, which binds to G-protein-coupled receptors. II type contains a p110 catalytic sub-unit-like. III type exist in yeast, which is composed of phosphoinositide 3-kinase vacuolar protein classification 34. PI3 K is an enzyme, a variety of growth factors can activate PI3 K, at the plasma membrane of activated PI3 K their substrate phosphorylation of phosphatidylinositol(3,4) –trisphosphate(PIP2) to convert for the second messenger phosphatidylinositol 3,4,5-trisphosphate(PIP3). Studies have shown that PI3 K signaling pathway plays an important role in promoting cell proliferation, inhibition of apoptosis, promote tumor angiogenesis and tumor cell migration and invasion.Ieucine-rich repeats and immunoglobulin-like domains-1 essence is a trans-membrane glycoprotein. LRIGs is a newly discovered class of genes, researchers have found that the family includes three members are: LRIGl, LRIG2, LRIG3. Nilsson etc which LRIG1 is found in the human genome and Drosophila Kekkon-1 gene homologous to a class of genes, the gene is located on human chromosome 3pl4.3 sites, biological behavior may be negative regulation of growth factors, in addition to maintain the stability of epithelial stem cells. LRIG1 gene encodes a leucine-rich repeats and immunoglobulin-like polypeptides, including the results of three parts: 1,an extracellular matrix: mainly containing 15 leucine-rich repeating units(LRR) and three immunization immunoglobulin-like domain(Ig) by a group of signal peptide;2, a transmembrane segment;3 intracellular tail of the receptor tyrosine kinase can inhibit the negative feedback. LRIG1 wide range of human existence and the various organizations and the organizations of different content. Hedman has been found that LRIG1 product in the brain, heart, kidney, skeletal muscle, stomach and testis high content; which is the highest expression of the brain, the lowest for the spleen, a difference of 240 times. Nilsson and Hedman use RT-PCR and Western blot technique method to analyze the expression LRIGlm RNA and protein sources in a variety of epithelial tumor cells, who found that LRIG1 expression levels in tumor tissue is missing or significantly reduced in 2002. Through this study, further research and confirmed that LRIG1 may be a tumor suppressor gene.Purpose Detection of PI3 K and LRIG1 express in esophageal squamous cell carcinoma and normal esophageal, analysis of chemotherapy for non-surgical treatment efficacy in patients with esophageal squamous cell carcinoma and prognostic factors, and provide the results of a single center in order to improve the survival rates of esophageal squamous cell carcinoma.Methods 56 cases of esophageal carcinoma were marked in North of Anhui Province from Coal Group General Hospital Department of Radiation Oncology patients completed chemotherapy or radiotherapy in May 2008-May 2010.Using immunohistochemical methods to detect 56 cases and 20 cases of esophageal tissue expression in normal esophageal tissues LRIG1 and PI3 K gene, combined with analysis of the relationship between the clinical and pathological features of 56 cases of tumor tissue expression of PI3 K and LRIG1 and clinical characteristics of patients. Chemoradiotherapy group 31 cases, radiotherapy group 25 cases, receive concurrent chemoradiotherapy in patients who chemotherapy drugs for FP(fluorouracil 1000 mg / m2 / d1 ~ d5 + cisplatin 40 mg / m2 / d1 ~ d3) or TP(paclitaxel 135 ~ 175 mg / m2 / d1 + cisplatin 40 mg / m2 / d1 ~ d3) scheme is repeated three to four weeks. Enrolled 56 cases of esophageal squamous cell carcinoma underwent radiotherapy, con-formal radiotherapy plan for a long time to wait for conventional radiotherapy, con-formal radiotherapy after 11 cases. 6m V-X line using linear accelerator 1.8~2.0Gy/times, 1 time/day, 5 times/week. Conventional radiotherapy dose DT34~38Gy; con-formal radiotherapy dose DT20~66Gy, the median dose 64 Gy. Comparing the expression of PI3 K and LRIG1 positive expression group and PI3 K and LRIG1 negative short-term and long-term efficacy, and to explore the expression of PI3 K and LRIG1 with esophageal squamous cell carcinoma chemotherapy sensitivity relationship. Using the SPSS 20.0 statistical software, Kaplan-Meier test method used in uni-variate analysis, comparing survival curves between the two groups of hypothesis testing using the log-rank method, Cox proportional hazards regression model was applied to multivariate analysis. P <0.05 was statistically significant.Results The positive expression rate of PI3 K protein in esophageal squamous cell carcinoma were 78.6%(44/56), the positive rate was 15.0% in normal esophageal tissues(3/20), the difference was statistically significant(P <0.05). The positiveexpression rate of LRIG1 protein in esophageal squamous cell carcinoma were 58.9%(33/56), the positive expression rate of normal esophageal tissue of 95.0%(19 of 20), the difference was statistically significant in(P <0.05).PI3 K positive rate in TNM stage(III, IV period), lymph node metastasis and distant metastasis-positive expression rate in TNM stage(I,IIperiod), without lymph node metastasis and distant metastasis-negative group(P values were <0.05); LRIG1 protein in gender, age, tumor location, cell differentiation, TNM stage, lymph node metastasis, distant metastasis, treatment methods, and the positive rate did not show statistically significant.Radiotherapy group had 5 cases of complete remission, partial remission in 10 patients, disease progression in patients with stable or have eight cases,the treatment rate was 65.2%; chemotherapy group had 11 cases of complete remission, partial remission there are 18 cases, stable or progressive disease in 4 patients, the treatment rate was 87.8%(χ2 = 4.134, P = 0.042), there was significant difference between the two groups.3-year survival of radiotherapy plus chemotherapy group was 48.5%, three-year survival rate with radiotherapy alone group was 43.5%, the overall survival rate between the two groups of patients, results showed no significant difference between the two groups(P = 0.677).Conclusion PI3 K protein expression in esophageal squamous carcinoma tissues was higher than normal group,the difference was statistically significant(P<0.05), suggesting that over-expression may be associated with the occurrence of esophageal cancer. Meanwhile, the correlation analysis showed that PI3 K protein expression and TNM stage, lymph node metastasis and distant metastasis, suggesting the formation of PI3 K with esophageal cancer. Expression in esophageal cancer LRIG1 protein was significantly lower than in normal tissues, the positive expression LRIG1 protein, the difference between the two groups was statistically significant(P <0.05). The results also show that LRIG1 protein in gender, age, tumor location, cell differentiation, TNM stage, lymph node metastasis, distant metastasis, and other aspects of treatment, thepositive rate did not show statistical significant. The results of studies have shown that the expression of PI3 K and LRIG1 in esophageal squamous cell carcinoma showed a negative correlation were statistically significant(P <0.05). PI3 K efficiency recent positive group(72.7%) lower than the PI3K-negative group(100.0%), in relation to the dominant negative short-term effect, three-year productivity shows no different prognosis(P = 0.147). LRIG1 efficiency recent positive group(87.9%) than LRIG1 negative group(65.2%), the positive short-term effect in terms of the dominant group,3-year productivity shows no different prognosis(P = 0.706).
Keywords/Search Tags:Esophageal neoplasm, PI3K, LRIG1, Radiotherapy, Chemotherapy
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