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The Relationship Between GLUT-1,HIF-1α And PI3K/Akt Expression And Prognosis Of Patients With Laryngeal Carcinoma Received Postoperative Radiotherapy

Posted on:2016-10-12Degree:MasterType:Thesis
Country:ChinaCandidate:G F ZhengFull Text:PDF
GTID:2334330482457538Subject:Otorhinolaryngology
Abstract/Summary:
Background:Laryngeal carcinoma is a common malignant tumor in the head and neck, and the prognosis factors are many, and the factors affecting the prognosis are not clear. Tolerance and high energy requirement of malignant tumor are essential to tumorigenesis, invasion and metastasis. The occurrence and development of tumor are closely related to the hypoxia microenvironment. The hypoxia inducible factor-1 (HIF-1) is a marker of tumor hypoxia, which plays an important role in malignant tumor. Abnormal glucose metabolism is another important feature of tumor tissues. Glucose transporter protein-1 (GLUT-1) is the most important protein. GLUT-1 is regulated by the hypoxia inducible factor. It is closely related to the cellular growth and proliferation of tumor cells. The phosphatidylinositol 3-kinase (P13K)/protein kinase B (Akt) pathway is an important signal molecule. Hypoxia can induce the activation of PI3K/Akt pathway, which can lead to a series of biological changes of tumor, and PI3K/Akt plays an important role in the regulation of GLUT-1 expression. This study was based on the previous studies, the expression of HIF-1α, GLUT-1, PI3K and p-Akt were detected by immunohistochemistry. To analyse retrospectively the correlation the clinical pathological features of 54 cases with laryngeal carcinoma received postoperative radiotherapy. The correlation between HIF-la, GLUT-1, PI3K and p-Akt expression clinical pathological features and prognosis was significant.Materials and Methods:The subjects were 54 patients with laryngeal carcinoma received postoperative radiotherapy in the First Affiliated Hospital of Zhejiang University from August 2013 to January 2009. The expression levels of HIF-la, GLUT-1, PI3K and p-Akt were detected by immunohistochemistry methods. The clinical and pathological features of laryngeal carcinoma were retrospectively analyzed. Data analysis using SPSS20.0 statistical software for processing. The relationship between HIF-1α, GLUT-1, PI3K, and p-Akt expression and clinical pathological data analysis using Chi-square test, correlation analysis using Pearson test, Overall survival count using the Kaplan-meier method, univariate analysis using the Log-rank method, multivariate analysis using Cox proportional hazards method, P<0.05 was statistically significant.Results:The average age of 54 patients with laryngeal cancinoma was 61.3 years (37 to 77 years). Thirty-one, twenty-two, and one patients had tumors located in the supraglottis, glottis and subglottis, respectively. Of the fifty-four patients, fifty-one had squamous cell carcinoma and three had small cell carcinoma. The TNM categories:T1N0M02 cases,T1bN0M01 case,T1N1MO 4 case,T2N0M016 cases, T2N1M06 cases, T2N2M0 1 case, T3N0M05 cases, T3N1M04 cases, T3N2M04 cases, T3N2aM01 cases, T4N0M06 cases, T4N1M02 cases, T4N2M01 case,T3N3M01 case, clinical stage phase Ⅰ 3 cases, II 16 cases, III 19 cases and Ⅳ 16 cases. In two cases,1 case had esophageal carcinoma and 1 case had prostate cancer. All patients were followed to September 24,2015, up from 6 months to 90 months, with an average of 38 months. In 54 cases:9 cases dead,3 cases lost,5 cases with local recurrence,30 cases with cervical lymphnode metastasis,3 cases with distant metastasis.2-year and 3-year survival rate were 95.0% and 76.0%. Univariate analysis showed that survival was significantly associated with T stage, clinical stage, and distant metastasis. Multivariate analysis showed that survival was not significantly associated with age, smoking, drinking, tumor primary site, T stage, clinical stage, lymphnode metasis, distant metasis and recurrence. In our series,64.8%(35/54),87.0%(47/54),37.0%(20/54) and 77.8%(42/54) were positive expression for HIF-la, GLUT-1, PI3K and p-Akt protein, respectively. Multivariate analysis showed that HIF-la, GLUT-1, PI3K, and p-Akt expression were not correlation with survival. Pearson analysis showed correlations between GLUT-1 and HIF-1α(r=0.312, P=0.022), p-Akt (r=0.457, P=0.001), and there was no correlation between HIF-la and PI3K, p-Akt (r=0.054, P=0.697 and r=0.189, P=0.171), GLUT-1 and PI3K (r=0.182, P=0.188).Conclusions:1. Univariate analysis showed that survival was significantly associated with T stage, clinical stage, distant metastasis and PI3K. Multivariate analysis showed that survival was not significantly associated with age, smoking, drinking, tumor primary site, T stage, clinical stage, lymphnode metasis, distant metasis, recurrence, HIF-la, GLUT-I, PI3K and p-Akt positive expression.2. There were correlation between increased PI3K and lymphnode metasis of laryngeal carcinoma.3. The expression of GLUT-1 was correlated between HIF-la and p-Akt expression.
Keywords/Search Tags:laryngeal carcinoma, immunohistochemistry, glucose transporter-1 hypoxia inducible factor-1α, PI3K/Akt pathway, prognosis, radiotherapy
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