The Expression And Significance Of PD-L1, SIRT1 In Colorectal Cancer

【Objective】To investigate the morphological expressions of PD-L1 protein and SIRT1 protein using immunohistochemistry(IHC) in colorectal cancer(CRC) clinical samples, and to explore the relationship between the expressions of these two proteins and clinicopathologial characteristics as well as prognosis value of colorectal cancer patients.【Methods】1. The first part: Specimens of 185 colorectal cancer patients were collected for the study, which were surgically resected and diagnosed by pathologists in Fuzhou general hospital of Nanjing military command from June 2008 to November 2009. 163 cases were collected complete clinical information and follow-up datas. IHCstaining was used for the detection of PD-L1 and SIRT1 morphological expressions; and furthermore, correlation analysis was done to study the relationship between them and clinical pathlogical parameters. 2. The second part: To investigate the clinical significances in prognosis of the expressions of PD-L1 protein and SIRT1 protein in 163 CRC. 163 CRC samples with full cilinical informations were divided into four independent groups by the expressions of PD-L1 protein(positive or negative/weak positive) and SIRT1 protein(positive or negative/weak positive), and further research was using to analyze the relationship between the expression of two kinds of protein and prognosis.【Results】1. Eighty nine of 163 colorectal cancer specimens(54.6.%) were found PD-L1 protein positive expression using IHC. In statistical analysis, we found there were no significant positive correlation was found between the PD-L1 positive expression and age, gender, tumour location, tumour diameter, histologic type, cutting edge, vascular invasion, T stage, tumour grade, N stage, M stage, TNM stage and Dukes’ stage(p>0.05). 2. One hundred and eleven of 163 colorectal cancer specimens(68.1%) were found SIRT1 protein positive expression using IHC. In statistical analysis, we found there were no significant positive correlation was found between the SIRT1 positive expression and age, gender, tumour location, tumour diameter, histologic type, cutting edge, vascular invasion, T stage, tumour grade, N stage, M stage, TNM stage and Dukes’ stage(p>0.05).3. There is positive correlations between PD-L1 and SIRT1 expressions among colorectal cancer specimens(r = 0.169, p < 0.05).These results suggest that there may be a notable correlation between the expressions of PD-L1 and SIRT1. 4. The five-year survival rate is 59.5%(97/163) in all available 163 patients, the average overall survival time(OS) was 49.4 months and the median survival time was 39.0 months(0.5-77 months). The patients with PD-L1 positive expression showed significantly worse 5-year survival rate and OS than those with negative expression(47.2% vs. 74.3%, 43.3 months vs. 55.7 months, p<0.05). 5. In survival analysis, we found the CRC patients with SIRT1 positive expression showed significantly worse 5-year survival rate and OS than those with negative expression(49.5% vs. 78.8%, 45.3 months vs. 58.0 months, p<0.05). 6. In rank-sum test analysis, we found that the prognosis of four independent groups(PD-L1+SIRT1+group, PD-L1+SIRT1-group, PD-L1-SIRT1+group, PD-L1-SIRT1-group) had a significant difference(p<0.001). The patients in PD-L1 positive expression group(PD-L1+SIRT1+group) presented significantly worse five-year survival rate and OS than three other groups(PD-L1+SIRT1-group PD-L1-SIRT1+group, PD-L1-SIRT1-group). In addition, the prognosis of patients in PD-L1+SIRT1+group were worse than the PD-L1+SIRT1-group(40.3% vs. 72.7% for 5-year survival rate; 41.6 months vs. 52.5 months for OS; p=0.017). Moreover, the prognosis of patients between PD-L1-SIRT1+group and PD-L1-SIRT1-group showed no significant difference(65.9% vs. 83.3% for 5-year survival rate; 51.2 months vs. 61.9 months for OS; p=0.122).【Conclusions】The expressions of PD-L1 and SIRT1 protein in colorectal cancer samples had no significant correlations with the pathological parameters. However, the relationship between the expressions PD-L1 and SIRT1 was significant positively correlation. In colorectal cancer, either the positive expression of PD-L1 protein or SIRT1 protein suggests the 5-year survival rate of patients were pool. Moreover, when the two proteins are both positive at the same time, the patients have the worst prognosis.