Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive solid malignancies with poor survival rates. Only 20% of the patients are eligible for R0-surgical resection, presenting with early relapses, mainly in the liver. PDAC patients with hepatic metastases have a worse outcome compared to patients with metastases at other sites. Early detection of hepatic spread bears the potential to improve patient outcomes. Thus, this study sought for serum-based perioperative biomarkers allowing discrimination of early (EHMS ≤ 12 months) and late hepatic metastatic spread (LHMS > 12 months). Serum samples from 83 resectable PDAC patients were divided into EHMS and LHMS and analyzed for levels of inflammatory mediators by LEGENDplex^TM, which was validated and extended by Olink^® analysis. CA19-9 serum levels served as control. Results were correlated with clinicopathological data. While serum CA19-9 levels were comparable, Olink^® analysis confirmed distinct differences between both groups. It revealed significantly elevated levels of factors involved in chemotaxis and migration of immune cells, immune activity, and cell growth in serum of LHMS-patients. Overall, Olink^® analysis identified a comprehensive biomarker panel in serum of PDAC patients that could provide the basis for predicting LHMS. However, further studies with larger cohorts are required for its clinical translation.

Objective: Borderline personality disorder (BPD) is characterized by intense mood swings, impulsivity, self-injurious behavior, poor anger control, fear of abandonment, and unstable interpersonal relationships. BPD is also associated with a heightened risk of cardiovascular disease, whereby the underlying mechanisms are insufficiently understood. Accordingly, the present study set out to examine whether individuals with BPD would show abnormal myocardial deformation and to explore the role of potential risk factors, including maladaptive stress responsivity, childhood trauma, and current stress exposure. Methods: Fifty female patients diagnosed with BPD and 50 controls matched for sex and age underwent echocardiography to determine the global longitudinal strain (GLS) of the left ventricle. In addition, childhood trauma, chronic stress, and “allostatic load” were determined, as well as borderline symptom severity and common risk factors for cardiovascular disease. Results: Aside from a significantly greater GLS in BPD patients, a multivariable regression analysis revealed that allostatic load (β = 0.225, p = .048) was significantly associated with GLS, with childhood trauma (β = 0.279, p = .062) approaching significance. Conversely, smoking (p = .867), chronic stress (p = .193), and borderline symptom severity (p = .342) were not associated with GLS, even though bivariate correlations were significant. Conclusions: Somatically healthy women with BPD display subtle signs of increased GLS, which is associated with allostatic load as an indicator of the “wear-and-tear” of the body. The association between childhood trauma with GLS was of similar strength but did not reach the threshold for statistical significance. This finding may support the need for primary prevention of somatic consequences of maladaptive stress responsivity in psychiatric patients.

Background: Colorectal cancer (CRC) is frequently associated with metastasis, resulting in high mortality rates. Platelets are known to play a crucial role in the metastatic cascade influencing tumor microenvironment remodeling, promoting cell transformation, facilitating metastatic niche formation, and shielding circulating tumor cells from immune surveillance. However, platelet proteomic alterations during tumor cell-induced platelet aggregation (TCIPA) remain largely unexplored. This study aims to characterize the proteomic profile of TCIPA in CRC using an in vitro model that recapitulates key aspects of CRC metastasis. Methods: TCIPA was assessed via light transmission aggregometry using an in vitro model incorporating paired primary and metastatic cell cultures. Stable Isotope Labeling with Amino Acids in Cell culture (SILAC) allowed for the discrimination of healthy platelet and tumor cell proteomes prior to and following TCIPA. Data-independent acquisition mass spectrometry was employed to analyze intra- and extracellular tumor and platelet proteomes. Comparative proteomic profiling was performed using a range of bioinformatic analyses, including clustering, differential expression, and Gene Set Enrichment Analyses (GSEA). Results: Comparison of the baseline proteome profiles of the CRC cell lines SW480 and SW620 identified 263 significant differentially expressed proteins (FDR ≤ 0.05, log ₂ FC ≥ 1). The GSEA demonstrated enrichment of the ‘epithelial-mesenchymal transition’ (FDR: 5.617 × 10 ⁻⁵ ) gene set in SW480 cells. While SW480 exhibited rapid TCIPA, SW620 did not consistently interact with healthy platelets. Following TCIPA, 34 tumor proteins showed differential expression compared to their naïve status (without platelet-exposure). Notably, 17 of these proteins were significantly associated with CRC progression, particularly in the promotion of EMT, metastasis, tumor cell survival, proliferation, and metabolic reprogramming. Conclusions: This study successfully characterized the proteomic profiles of platelets, platelet secretomes, and colorectal tumor cells following TCIPA-induced activation. The findings highlight the significant role of several tumor proteins and their metabolic effects in colorectal cancer progression, particularly with regard to metastasis.