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Prognostic and Predictive Role of JWA and XRCC1 Expression in Gastric Cancer: a Retrospective Study of Three Large Cohorts

Author: DingJingJing
Tutor: ZhouJianWei
School: Nanjing Medical University
Course: Occupational and Environmental Health
Keywords: Gastric cancer Prognosis JWA XRCC1 Oxaliplatin
CLC: R735.2
Type: Master's thesis
Year: 2011
Downloads: 34
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Abstract

Background: The gastric cancer in China high incidence of, standardization surgery patient prognosis is quite different, yet personalized assessment of prognosis. Adjuvant chemotherapy can theoretically remove residual tumor cells, played the role of prevention of tumor recurrence and metastasis, but its role is less consistently great individual differences, remains controversial. The base excision repair molecular JWA and XRCC1 play an important role in the development and progression of cancer. Objective: To investigate the JWA and XRCC1 expression in gastric cancer tissues indicators of level of patient clinical and pathological features and postoperative survival and efficacy of chemotherapy, found to predict the prognosis of gastric cancer biomarkers and gastric cancer individualized treatment programs choose to provide scientific basis. Methods: May 1990 -1995 in December at the Cancer Hospital of Nantong City of patients with gastric resection (142 cases), as a pilot group. Select the hospital from November 2000 to April 2005 all patients with gastric cancer resection patients (640 cases), as a validation group 1. January 1999 to December 2006 in Yixing City People's Hospital for gastric resection in all patients (1016), as a validation group 2. In cases of complete clinical and pathological data for the study, all cases were confirmed by postoperative pathological examination confirmed by telephone, mail, household query on the follow-up of patients with gastric cancer by participating hospitals. Retrospectively reviewed the medical records of all cases clinical data after the approval of the information by the hospital to collect, double-blind entry, collated into a database. Three samples of all patients with gastric cancer pathology wax block to entrust a professional chip companies making tissue microarray, JWA and XRCC1 expression levels in the gastric cancer tissues detected by immunohistochemistry. Gastric cancer patients undergoing clinical, pathological factors of JWA and XRCC1 expression levels and prognosis the COX single and multivariate correlation analysis. Analysis of the data using SAS 9.1.3, to P lt; 0.05 for test of significance level. Access to and use of all the samples after review of the medical ethics committee of Nanjing Medical University agreed to jointly approved and Cancer Hospital of Nantong City, Yixing City People's Hospital. Results: the results in the test group showed cancer tissue JWA and XRCC1 protein level was significantly lower than the adjacent tissues, cancer tissues JWA and XRCC1 expression level with clinicopathological characteristics and prognosis, etc. significantly related, while the adjacent tissue JWA and XRCC1 has nothing to do with the clinicopathological features and prognosis. Therefore no longer in the validation group analysis of the results of the adjacent tissues. JWA and XRCC1 expression levels in gastric cancer tissues in three queues showed a high level of consistency, namely: the experimental group, r = 0.766, P lt; 0.001; validation group 1, r = 0.815, P lt; 0.001 ; validation group 2, r = 0.249, P lt; 0.001 (Spearman rank correlation test). JWA and XRCC1 expression levels of cancer tissue to reduce the depth of invasion, lymph node metastasis, TNM stage, degree of differentiation and poor prognosis are related. Adjacent tissues, however, the JWA and XRCC1 level with clinicopathological parameters and prognosis. Multi-factor Cox regression model showed that JWA and XRCC1 gastric independent prognostic factors (JWA: HR = 0.20, 95% CI = 0.12-0.34; XRCC1: HR = 0.28, 95% CI = 0.17-0.47). This conclusion has been verified in the other two queues. Validation group 2, 93 patients received 5 - fluorouracil, leucovorin, and oxaliplatin combination chemotherapy, the prognosis is better than surgery alone patients (log-rank test, P = 0.003). JWA low expression patients benefit from the chemotherapy (HR = 0.49; 95% CI = 0.31-0.76; log-rank test, P = 0.004), however, the high expression of JWA patients chemotherapy or prognosis there is no significant difference (HR = 0.54; 95% CI = 0.28-1.06; log-rank test, P = 0.282). Conclusion: the base excision repair the molecule JWA and XRCC1 In the expression level of gastric cancer tissues was significantly lower than the adjacent tissues, and may play an important role in tumorigenesis. JWA and XRCC1 protein levels in the cancer tissue and the depth of tumor invasion, lymph node metastasis, TNM staging, was the relationship between the degree of differentiation. Adjacent tissues showed no correlation with the above indicators. Useful molecular markers of prognosis in cancer tissues JWA and XRCC1 protein expression levels may predict patients with gastric cancer after surgery, patients select individual oxaliplatin treatment programs target.

Prognostic and Predictive Role of JWA and XRCC1 Expression in Gastric Cancer: a Retrospective Study of Three Large Cohorts

Abstract

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