In this study, we conducted a battery of laboratory tests on patients with PC to uncover disparities when compared to control subjects. Our investigations revealed distinct patterns, including a propensity toward anemia, heightened coagulation tendencies, compromised immune function, pro-inflammatory responses, and glucose metabolism dysfunction among PC patients. Employing Pearson's correlation analysis, we discerned robust associations among markers indicative of pro-coagulation, pro-inflammation, and pro-tumorigenic processes. Additionally, clustering analysis underscored the tight association between coagulate and inflammatory factors in PC. Collectively, these findings contribute to an enhanced comprehension of the intricate pathophysiological landscape characterizing PC and its associate complications.
One notable aspect of PC is its association with a hypercoagulate state, which can lead to thrombotic complications in up to 30% of cases [19]. This hypercoagulate state is predominantly attributed to elevated TF levels and heightened platelet activation. TF, expressed abundantly on malignant exocrine pancreatic cells and within the tumor microenvironment, precipitates coagulation cascades by binding with factor VII, leading to thrombin generation and subsequent platelet activation [20]. Activated platelets, in turn, facilitate thrombus formation through various mechanisms [21]. Consequently, lower extremity deep vein thrombosis, thrombophlebitis migrans, and pulmonary embolism frequently afflict PC patients, particularly during surgical, chemotherapy, or molecular targeted therapy interventions, elevating the risk to approximately 40–50% [22. 23]. Therefore, diligent monitoring of FIB and platelet function is imperative in averting thrombotic complications in PC. Within our study, we observed notable differences in the K and Angle indicators derived from r-TEG, both of which were significantly distinct from controls, signifying heightened FIB levels and an enhanced pro-coagulant state among PC patients. Additionally, we noted a considerable increase in MA, a pivotal indicator for assessing platelet function, which correlated strongly with PLT in PC patients, suggesting heightened platelet activation and proclivity toward clot formation. However, CCAs indicators (TT, APTT, INR) as well as PLT and PDW exhibited negligible changes and weaker correlations with thrombotic components. These combined findings underscore the utility of r-TEG combined with CCAs in identifying hypercoagulate or pro-thrombotic states in PC patients, aiding in the prevention of thrombotic complications.
Beyond pro-coagulant factors, malignant pancreatic cells incite the secretion of pro-inflammatory factors, thereby creating a pro-tumorigenic microenvironment. Particularly, IL-6, a potent inflammatory cytokine, can be induced by pancreatic tumors in fibroblasts through a paracrine positive feedback loop [18]. Previous studies have linked circulating IL-6 levels to tumor burden and prognosis in PC patients [24–26]. Our study consistently revealed a significant elevation in circulating IL-6 levels among PC patients. Intriguingly, we observed strong correlations between IL-6 and coagulation factors, further underscoring the synergistic influence of pro-coagulate and pro-inflammatory elements on the pro-tumorigenic processes. Notably, preclinical data and animal models have indicated the efficacy of IL-6 blockers in attenuating pancreatic tumor progression and related complications [26–28]. Thus, a combination of anti-inflammatory and anti-thrombotic therapies holds promise for PC treatment and complication prevention.
Additionally, we observed significantly elevated serum tumor markers, CA19-9 and CEA, in PC patients compared to controls, consistent with studies previously [29–32].Although they are well-performing tumor biomarkers, researchers have been exploring other potential markers for the early detection of PC. Some markers, including microRAN-21 and RAD51, have been found to be predictive of pancreatic cancer [33, 34]. In our study, we discovered that multiple machine learning models based on coagulation factors can be used for predicting PC. These findings suggest the potential utility of coagulation markers in predicting or evaluating disease progression and prognosis. However, further research is needed to explore whether targeting these factors could mitigate the progression of PC and protect patients from thrombotic events.
Despite these insights, our study has limitations, including the absence of a comparative analysis of indicators among PC patients at different TNM stages, the potential influence of underlying abnormalities in control subjects, and the lack of longitudinal patient follow-up. In conclusion, our study contributes to our understanding of hematological and coagulation abnormalities in PC, emphasizing the intricate interplay between pro-coagulant, pro-inflammatory, and pro-tumorigenic factors. These findings hold implications for PC prevention, diagnosis, and treatment, highlighting the importance of monitoring coagulation markers and inflammation in clinical practice. Further research is warranted to validate and expand upon these findings, potentially leading to improved management strategies for individuals affected by PC.