| Objective:We aim to investigate the expression of SIRT3 in pancreatic cancer and its clinical association in pancreatic cancer patients.Methods:1. 79 samples were collected from PC patients who underwent surgical resection at Fuzhou General Hospital of Nanjing Military Command, Fuzhou, China, during May 2005 to April 2014. Formalin-fixed paraffin-embedded cancer and its non-cancer tissue counterpart were used. Before surgery, all the patients did not receive any kinds of therapeutic regimen, such as chemotherapy, radiotherapy or targeted therapy.2. Immunohistochemistry was performed to evaluate expression of SIRT33. All slides were independently evaluated by two pathologists who were blinded to the clinicopathologic and survival data. The brown cytoplasm coloration was considered as the positive signal. SIRT3 scores were divided into two groups: negative and positive. Non-immune rabbit serum diluted at the same concentration with monoclonal antibody to SIRT3 was served as negative control.4. Follow-up was performed for all the patients through telephone call and/or outpatient clinic.5. SPSS 18.0 software(SPSS Inc, Chicago, IL, USA) was used to perform all the analysis. We utilize Chi-square test to analysis the relationship between SIRT3 expression and the clinicopathological characteristics of patients. Mc Nemar's test was adopted to compare SIRT3 expression between cancer and adjacent non-cancer tissues. Besides that, we use Pearson's correlation analysis to further investigate the relationship between them. Kaplan-Meier method was applied to plot survival curve and the difference between these two curves was verified by log-rank test. Multivariate Cox regression(Proportional hazard model) analysis was conducted to determine independent prognostic factors. Two sides P value less than 0.05 was deemed as statistically significant.Results:1. SIRT3 negative expression rate in cancer tissues was 60.7%(48/79), while in adjacent non-cancer tissues this ratio low to 26.6%(29/79). SIRT3 negative expression was more common in cancer tissues than in adjacent non-cancer tissues(P<0.001, Mc Nemar's test).2. The expression of SIRT3 protein correlated with surgery marginal(p=0.028), T status(p<0.001) and tumor stage(p=0.013). No significant relationship with other clinicopathologic parameters was found.3. The average OS time for patients in SIRT3 positive expression group was 18.81±3.38 months, however it was only 8.06±0.80 months for patients in SIRT3 negative expression group. Patients in SIRT3 negative expression group had poorer OS(P=0.001) than patients in SIRT3 positive expression group, according to Kaplan-Meier survival analysis and log-rank test.3. According to univariate analysis, cell grade, tumor size, T status, N status, peri-neural invasion, tumor stage and SIRT3 expression were identified to be correlated with OS. In multivariate cox regression, SIRT3 negative expression was proved to be a significant independent prognostic factor for poor OS in PC patients(HR=1.83, 95% CI 1.00-3.33, P=0.049). Other independent prognostic factor was cell grade(p=0.016).4. Univariate analysis indicated SIRT3 expression as a significant predictor for overall survival in 12 subsets of PC patients, such as Males, Age<57, T1-2, N0, Age>57, Tumor size(?2cm), PNI present or absent, Tumor stage(I-II), Cell grade(well-moderate), R0 resection and Pancreatic head(P<0.05). Multivariate analysis defined that SIRT3 expression was independent prognostic indicator in 4 of the above 12 subgroups, including Males, PNI present, Cell grade(well-moderate), R0 resection and Pancreatic head(P<0.05)Conclusions:Down-regulated SIRT3 may contribute to tumor progression and gloomy prognosis in PC patients and may sever as a novel prognostic marker. |
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