Clinical Significance Of The Expression Of PD-1 In Colorectal Cancer

Objective In recent years,a number of studies have found that programmed death-1(PD-1) high level expressed in several malignant solid tumors, such as malignant melanoma and non-small cell lung cancer. To some extent, blocking the PD-1/PD-L pathway can inhibit the further development of these tumors. We conducted this preliminary experiment in order to study the clinical significance of the expression of PD-1 in colorectal cancer, we detected the expression of PD-1 in clinlic samples(peripheral blood, tumor and adjacent normal tissue of colorectal cancerpatients and peripheral blood of healthy volunteers) and in tumor-bearing models, andmade a preliminary analysisof the relationship between PD-1 expression and the parameters of colorectal cancer evolution. Set up a certain theoretical basis for the further exploration on the application value of PD-1 in the early diagnosis, immune target therapy and prognosis evaluation of colorectal cancer.Methods Soluble programmed death-1(s PD-1) levels were detected by enzyme-linked immunosorbent assay in serum samples of 88 colorectal cancer patients who received surgical treatment in the department of general surgery,the First Affiliated Hospital of Soochow University during January 2015 to September 2015 and 16 healthy volunteers in the same period. The expression of PD-l on CD3+ T cells in peripheral blood samples that collected from 88 colorectal cancer patients and 74 healthy volunteers were measured using flow cytometry(FCM). Moreover, the expression of PD-l on CD3+ T cells in tumor and adjacent normal tissue of 6 colorectal cancer patients were also detected by FCM.Balb/c mice tumor-bearing models were constructed by subcutaneous implantation of CT26 tumor cell line, the changes of positive expression rate of PD-1 on CD3+T cells in the spleen and transplanted tumor tissues werealso detected by FCM. The relationship between PD-1 expression and the parameters of colorectal cancer evolution were all analyzed.Results1.The average expression level of s PD-1 in serum of colorectal cancer patients [(131.14±91.91) pg/ml] was higher than that in healthy volunteers [(83.07±65.47) pg/ml], and the difference was statistically significant(P<0.05). At the same time, s PD-1 expression level was closely related to the degree of tumor differentiation, lymph node metastasis and clinical pathological stage of colorectal cancer patients, the level significantly increased in colorectal cancer patients with lower degree of differentiation, lymph node metastasis or higher Dukes stage.2. PD-1 positive expression on the surface of CD3+T cell was significantly increased in colorectal cancer patients [(29.25±9.37) %] compared to healthy volunteers [(19.35±7.37) %], the differencewas of obvious statistic significant(P<0.01). PD-1 positive expression rate was also significantly increased in colorectal cancer patients with lower degree of differentiation, lymph node metastasis or higher Dukes stage.3.PD-1 positive expression rate on CD3+T cells in colorectal cancer tissue [(52.38± 12.28) %] was significantly higher than that in adjacent normal tissue [(24.72±4.78) %], and the difference was significant(P<0.01).4.In the colon cancer tumor-bearing mice model, along with the growth of transplanted tumor, PD-1 positive expression rate on the CD3+T cell of tumor-bearing mice spleen and transplanted tumor showed a gradually rising tendency. Average positive expression rate of PD-1 on the CD3+T cell of tumor-bearing mice spleen raised from(52.83±6.17)% to(77.30±6.84)%, and average positive expression rate of transplanted tumor raised from(60.43±2.77)% to(90.47±4.31)%.Conclusions PD-1 expression level and positive expression rate of PD-1 on CD3+T cell were all highly expressed in the peripheral blood of colorectal cancer patients and all positively correlated with the severity of colorectal cancer.Positive expression rate of PD-1 on CD3+T cell in colorectal cancer tissue was significantly higher than that in adjacent normal tissue.In colon cancer tumor-bearing mice model,with the increase of transplanted tumor volume, positive expression rate of PD-1 on CD3+T cellin spleens and transplanted tumor tissues showed gradual upward trend.Above all, PD-1 is expected to play an important role in the early diagnosis, targeted therapy and prognosis in colorectal cancer.