Pancreatic cancer is a highly malignant tumor with a very poor prognosis. The five-year
survival rate is only 10%, and its incidence is significantly increasing worldwide. Early
diagnosis and treatment can improve the survival of pancreatic cancer patients. However, the
early diagnosis of pancreatic cancer is extremely difficult, and more than 50% of patients
have distant metastasis at the time of diagnosis. Therefore, the development of sensitive and
efficient serum biomarkers for pancreatic cancer has important clinical significance.
Pancreatic cancer has a special microenvironment. Pancreatic cancer cells are only 10 to 30
percent, while inflammatory cells are more than 50 percent. The interaction between
inflammatory cells and tumor cells promotes the development of pancreatic cancer. CD58 is an
important immune adhesion molecule, which exists in the membrane (mCD58) and soluble (sCD58)
states. For the first time, the investigators found that macrophages can promote CD58
expression separation in pancreatic cancer cells through TGFβ1, that is, the expression of
mCD58 decreased and the release of more sCD58. SCD58 competitively binds CD2 on T/NK cells,
thereby inducing immune suppression and promoting the development of pancreatic cancer.
Therefore, the investigators propose a scientific hypothesis that serum sCD58 and TGFβ1 can
be used as markers of tumor burden and tumor immunosuppression status in pancreatic cancer.
They have important value in the diagnosis, immunotyping, and prognosis of pancreatic cancer.
To test this scientific hypothesis, the investigators obtained peripheral blood serum from
132 healthy controls, 131 patients undergoing pancreatic cancer surgery, 80 patients with
low-grade malignant pancreatic tumors, 58 patients with benign pancreatic tumors, and 16
patients with chronic pancreatitis as a training cohort. The expression levels of sCD58 and
TGFβ1 in serum were detected by Elisa. The results showed that the expression levels of sCD58
and TGFβ1 in peripheral blood were significantly higher in pancreatic cancer, but there was
no significant difference in sCD58 and TGFβ1 between other pancreatic diseases and healthy
people. The expression levels of sCD58 and TGFβ1 were positively correlated with the clinical
stage of pancreatic cancer. The level of sCD58 is negatively correlated with the prognosis of
pancreatic cancer patients. The three-factor diagnostic model of sCD58, TGFβ1 and CA199 can
improve the diagnostic efficiency of pancreatic cancer, especially when CA199 is disabled,
sCD58 and TGFβ1 still have high diagnostic efficiency. However, this previous study still had
the following shortcomings :(1) patients with advanced pancreatic cancer were not included;
(2) The relationship between serum sCD58 and TGFβ1 and the efficacy of chemotherapy was not
clarified. (3) The effects of immune diseases and infection on serum sCD58 and TGFβ1 were not
considered; (4) The included sample size is small. Based on the previous study, this study
plans to expand the sample size by 2 times as the validation cohort. The clinical value of
serum sCD58 and TGFβ1 as biomarkers for diagnosis, immunotyping and prognosis prediction of
pancreatic cancer was fully clarified by using pre-mature detection methods and modeling
methods to improve the above four deficiencies. To develop a kit combining sCD58, TGFβ1 and
CA199, improve the early diagnosis and treatment rate of pancreatic cancer, guide accurate
immune typing and optimize individualized treatment, and finally prolong the survival time of
patients.