Elevated Circulating Levels of N-Acetyl-Seryl-Aspartyl-Lysyl-Proline ( AcSDKP) Involved in Pancreatic Cancer Development
Background: Pancreatic cancer is the fourth leading cause of patient mortality with poor early prognosis. Lack of symptoms as early detection of this cancer has become the major problem for its clinical investigation. Thymosin β-4 (Tβ4) has been associated with angiogenesis and metastasis in pancreatic cancer. Recently, N-Acetyl-Seryl-Aspartyl-Lysyl-Proline (AcSDKP), a cleavage and active form of Tβ4, is suggested related to systemic alteration to patients and involve in the Pancreatic Ductal
... Pancreatic Ductal Adenocarcinoma (PDAC) progression. However, the way this systemic change affected PDAC development is still not fully elucidated. This case-control study was conducted to evaluate the level of AcSDKP in health and pancreatic cancer patients during the progression of pancreatic cancer development. Methods: We analyzed 105 patients, including 15 healthy subjects and 90 pancreatic cancer subjects. The levels of AcSDKP were analyzed by Enzyme-Linked Immunosorbent Assay (ELISA) kit. Proliferation rate analysis was conducted using MTS assay in AsPC, HPAC, and PANC-1 cell line pre-treated by prolyl oligopeptidase (POP) inhibitor and AcSDKP polypeptide. Results: Compared to healthy patients (0.73 ± 0.13), the levels of AcSDKP significantly increased in pancreatic cancer subjects (1.34 ± 0.14). AcSDKP induced pancreatic cell proliferation while inversely inhibited with POP inhibitor by in vitro analysis. Moreover, levels of AcSDKP were strongly positively correlated with pancreatic cancer status (r = 0.278, p = 0.026), betatrophin (r = 0.270, p = 0.025), ALP (r = 0.267, p = 0.034), ALT (r = 0.336, p = 0.007), and AST (r = 0.255, p = 0.042), while inversely correlated with cholesterol levels (r = - 0.250, p = 0.046). Furthermore, in univariate and multivariate binary logistic regression analysis, the levels of AcSDKP showed a strong association with pancreatic cancer [(p = 0.031, OR±95%CI = 3.342 (1.117-10.002)] and [(p = 0.024, OR±95%CI = 4.324 (1.030-18.148)]. Quintile analysis showed that the level of AcSDKP has a strong association with betatrophin [(p = 0.033, OR±95%CI = 5.623 (1.142-24.266)]. Conclusions: AcSDKP can contribute to the progression of pancreatic cancer incidence and may indirectly be associated with liver lipid metabolism hormone as well as tumor cell proliferation. AcSDKP might be a potential additional predictor for pancreatic cancer.