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Expression and Prognostic Significance of TS and BRCAl mRNA in Non-small Cell Lung Cancer

Author: YuDing
Tutor: YinLiu
School: Dalian Medical University
Course: Oncology
Keywords: Non-small cell lung cancer Disease-free survival Overall survival Chemotherapy TS BRCA1
CLC: R734.2
Type: Master's thesis
Year: 2011
Downloads: 18
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Abstract


Objective: To detect 160 cases of stage Ⅰ B ~ Ⅲ A non-small cell lung cancer patients (NSCLC) tissue thymidylate synthase (TS) and human breast cancer susceptibility gene 1 (BRCA1) investigate the expression of TS and BRCA1 expression Ⅰ B ~ Ⅲ A NSCLC patients after the clinical stage, pathological features, disease free survival (DFS) and overall survival (OS) correlation. Methods: (1) retrospectively analyzed the First Affiliated Hospital of Dalian Medical University from January 2004 to October 2007 surgery Ⅰ B ~ Ⅲ A NSCLC were 160 cases, 132 cases of adjuvant chemotherapy, no chemotherapy in 28 cases. Which, Ⅰ B of 74 cases, Ⅱ B of 22 cases, Ⅲ A period of 64 cases. Application of tissue microarray (tissue microar-ray TMA), hand-planted specimens were made of wax block microarrays, immunohistochemical assay samples and BRCA1 expression of TS, TS and BRCA1 expression analysis with sex, age, tumor histological type, degree of malignancy, clinical stage (TNM) and smoking-related indices, as well as the expression of TS and BRCA1 correlation; analysis affect the postoperative NSCLC patients DFS and OS independence of the prognostic factors. (2) application of χ2 test, Life Table, Cox multivariate regression analysis of the test results for statistical analysis. Results: (1) 160 cases Ⅰ B ~ Ⅲ A NSCLC, pathological tissues, TS expression was 51.9%, BRCA1 expression rate was 50.6%. No correlation between the expression of the two. (2) TS expression in NSCLC patients' sex, age, smoking index irrelevant. Different histological type, squamous cell carcinoma of the highest rates of TS expression, followed by adenocarcinoma, adenosquamous carcinoma minimum, the difference was statistically significant (P lt; 0.05); different degree of malignancy, poorly differentiated NSCLC, the highest rate of positive expression of TS, followed by moderately differentiated, well-differentiated minimum, the difference was statistically significant (P lt; 0.05); different clinical stages (TNM), with clinical stage, NSCLC, TS expression gradually increased, the difference was statistically significant (P lt ; 0.05). (3) BRCA1 expression in NSCLC patients' gender, age, histological type, degree of malignancy, clinical stage and smoking index unrelated (P gt; 0.05). (4) into the group of patients with NSCLC, median DFS was 28 months, the median OS was 46 months. TS-positive group than negative group median DFS extended (50vs22 months), median OS extended (60vs34 months), the difference was statistically significant (P lt; 0.05). BRCA1-positive group than negative group median DFS extended (34vs27 months), the difference was not statistically significant; median OS extended (55vs39 months), the difference was statistically significant (P lt; 0.05). (5) squamous cell carcinoma, adenocarcinoma, TS negative expression group than in the positive group DFS and OS extension, the difference was statistically significant (P lt; 0.05); in poorly differentiated NSCLC, TS-positive group than negative group DFS and OS extended , the difference was statistically significant (P lt; 0.05); Ⅱ B ~ Ⅲ A NSCLC patients, TS-positive group than negative group DFS and OS extension, the difference was statistically significant (P lt; 0.05); adenosquamous carcinoma compared with the number of cases less, do not compare; well differentiated and Ⅰ B NSCLC patients, TS expression on DFS and OS was no significant effect (P gt; 0.05). (6) squamous cell carcinoma, BRCA1-positive group than negative group DFS and OS extension, the difference was statistically significant (P lt; 0.05); well-differentiated NSCLC, BRCA1-positive group than negative group DFS and OS extension, the difference was statistically significance (P lt; 0.05); Ⅰ B NSCLC patients, BRCA1-positive group than negative group DFS and OS extension, the difference was statistically significant (P lt; 0.05). Adenosquamous carcinoma small number of cases, not be compared; adenocarcinoma, poorly differentiated and Ⅱ B ~ Ⅲ A NSCLC patients, BRCA1 expression on DFS and OS was no significant effect (P gt; 0.05). (7) into the group of 132 cases of adjuvant chemotherapy in NSCLC patients, TS-positive group than negative group prolonged DFS and OS (P lt; 0.05); disease progression after the application of pemetrexed chemotherapy extended TS patients with negative expression of the disease Progress survival time (P lt; 0.05). (8) BRCA1 expression on postoperative adjuvant chemotherapy in patients with DFS and OS, no statistically significant effect (P gt; 0.05); BRCA1 negative group applications NP, GP, TP scheme adjuvant chemotherapy, NP group DFS and OS GP and TP group compared with longer statistically significant (P lt; 0.05). (9) using Cox analysis showed: clinical staging, chemotherapy, TS expression is affected Ⅰ B ~ Ⅲ A stage NSCLC patients after DFS and OS independent prognostic factor. Conclusions: (1) TS was higher than in squamous carcinoma, the positive rate with tumor malignancy and clinical stage (TNM) increased gradually increased, BRCA1 positive expression rate and clinical, pathological features unrelated. (2) TS, BRCA1 expression on stage Ⅰ B ~ Ⅲ A NSCLC patients after DFS and OS influential, TS-positive and BRCA1-positive poor prognosis. (3) TS can be used as guidance NSCLC patients after chemotherapy treatment and predict drug efficacy indicators, TS-negative group after chemotherapy, the median DFS and median OS compared with positive group extended TS pemetrexed extend survival of patients with negative expression . (4) adjuvant chemotherapy in NSCLC patients, BRCA1 expression had no effect on its DFS and OS. (5) clinical staging, chemotherapy, TS expression is affected Ⅰ B ~ Ⅲ A stage NSCLC patients after DFS and OS independent prognostic factors.

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