It is known that pancreatic ductal adenocarcinoma is one of the high malignant degree of cancer. At present, several biomarkers for pancreatic cancer have been proposed for earlier diagnosis, there is no effective diagnostic method to find early pancreatic in clinical application cancer, surgical resection offers the chance to cure PDAC. But Most of PDAC patients have lost the opportunity of operation when pancreatic cancer was found. To found biomarkers for early diagnosis of pancreatic cancer propose future research directions[23–25].
Surgery is one of the most important therapy for pancreatic ductal adenocarcinoma. However, due to the limitation of diagnostic techniques, it is usually difficult to detect pancreatic cancer early, which leads to poor prognosis[24]. Some scholars had shown that some markers may be related to the prognosis of PDAC patients, for examples, differentiation grade and TNM stage[1,8]. These prognostic factors were difficult to judge preoperatively, so the study of preoperative serum markers had become a research hot spot[12,26]. As an independent prognostic indicator, CA19-9 had attracted more and more attention[26]. Level D-dimer was found to be associated with prognosis of digestive tumors[12,13]. But CA19-9 level may be affected by jaundice[18]and inflammatory[19], many pancreatic cancer patients complicated with jaundice.
In our study, patients with preoperative CA19-9 ≥ 176.66 U/ml had a high degree of malignancy and a short overall survival period, but the mechanism of CA19-9 and tumor progression was still unclear. CA19-9 was positively correlated with lymph node metastasis (P = 0.010), TNM stage (P < 0.001), survival ratio (P < 0.001). D-dimer degraded by plasmin during fibrinolysis was a degradation product of the cross-linked fibrinpolymer. Previous studies had showed that plasma level of D-dimer can predict poor prognosis in several types of malignant tumors, including ovarian[27], breast[28] and colorectal[29]. The D-dimer was positively correlated with differentiation grade (P = 0.014), tumor size (P = 0.045), TNM stage (P = 0.006) and survival ratio (P < 0.001). Apart from being a diagnostic marker for activation of coagulation and fibrinolysis, D-dimer also played an important role in cancer progression, invasion, and prognosis[29]. Recent research showed that activation of the coagulation system was associated with tumorigenesis development, dissemination and transfer[31,32]. Fibrinolytic enzymes in fibrinolytic systems played an important role in tumor invasion and penetration into the blood circulation. Studies had also shown that tumors were encapsulated in the network structure, as the disease developed and the rate of metastasis accelerated, the release of D-dimer increased after the destruction of the network structure, and thrombotic diseases were prone to occur[12,33,34].
A20 was significantly correlated with differentiation grade (P < 0.001), BMI (P < 0.001), TNM stage (P = 0.024) and survival ratio (P < 0.001). As a cytoplasmic zinc-finger protein, A20 was reported to be expressed in a variety of human cells, such as T lymphocytes and B lymphocytes[35,36], which had been reported to regulate dynamic immune responses by negatively mediating the activity of the transcription factor NF-κβ and the proinflammatory gene expression[14,37,38]. NF-κβ signaling pathways involved in regulating tumor proliferation and apoptosis. A20 participates in endothelial cell stress response and inflammatory response[15,21], which may be associated with D-dimer and CA19-9. Their mechanism is still unclear, which is also our next research direction.
A20 in PDAC was low expression, which found to be linked with TMN stage (P < 0.05). Other researchers suggested that expression of A20 was reduced in pancreatic cancer tissues, but not deeply associated with TNM stages[17]. The overall survival time of patients with CA19-9 < 176.66 U/ml (P < 0.001), D-dimer < 1.18 mg/L (P < 0.001) and high expression of A20 group (P < 0.001) was longer by Kaplan-Meier curves. The COX multivariate analyses showed that TNM stage (P = 0.007), differentiation grade (P < 0.001), CA19-9 (P = 0.005), D-dimer (P = 0.005) and A20 (P < 0.001) were independent prognostic markers for patients suffering from pancreatic ductal adenocarcinoma, which may be useful in evaluating the prognosis and progress of PDAC patients.
TNM stage and differentiation grade were not easy to be evaluated by imaging examination before operation, however, the levels of preoperative CA199 and D-dimer was easier to be detected, which may be helpful to evaluate the prognosis of pancreatic ductal adenocarcinoma patients. For patients with high levels of CA19-9 and D-dimer before operation, early intervention can be considered. We can not only use the CA19-9 and D-dimer level to judge the prognosis, but also A20, TNM stage and differentiation grade should also be considered comprehensively after the surgery.
We should make sufficient evaluation and preparation for the patients with PDAC before operation, and make the best individualized treatment plan for the patients. Follow-up should be carried out after operation to find early recurrence or metastasis to prolong survival time of patients. Therefore, by evaluation of relevant indexes before and after surgery, the optimal comprehensive treatment plan for PDAC patients was formulated, which may improve the prognosis of patients, which required a lot of further clinical and basic research.