搜索结果：pancreatic

For decades, we have viewed pancreatic fibrosis as a passive scar-the end-stage wreckage of chronic inflammation or a late accomplice of growing tumors. A recent study by He Ren and colleagues sheds critical light on the origins of the phenomenon tracing it to an unexpected cellular culprit: a rare subset of pancreatic epithelial cells that express FOXP3-a transcription factor predominantly associated with regulatory T cells. These epithelial FOXP3 (E-FOXP3) positive cells do not need oncogenic Kras or overt inflammation to ignite fibrosis. On their own, they orchestrate a glycosylation-dependent IL-6 switch that turns quiescent pancreatic stellate cells into a self-amplifying fibrotic machine. In discovering a proto-fibrogenic "trigger cell" that acts silently, long before any symptom or radiological sign, the work redefines the cellular hierarchy of pancreatic fibrocarcinogenesis. Further, the paper identifies a post-translational "sugar code" as a therapeutic foothold, and opens a long-sought preemptive window for intercepting pancreatic cancer at its most curable stage-before the desmoplastic fortress is ever built.

A 45-year-old man with a history of alcohol-induced chronic pancreatitis presented with acute abdominal pain and low-grade fever. Initial imaging with contrast-enhanced CT showed a widened portal vein containing fluid that appeared different from a typical solid clot. Further specialised magnetic resonance imaging (MRCP) confirmed a fistula connecting the pancreatic duct directly to the portal vein. On that MRCP imaging, there's evidence of intravascular fluid collection within the portal vein showing homogeneous T2-hyperintense signal characteristics with the adjacent pancreatic fluid, suggesting direct extension. An axial T2-weighted MRI confirmed the existence of the fistula. A review of a previous MRCP performed six months prior showed a pancreatic head pseudocyst already extending into the portal vein, suggesting that the fistula developed gradually over several months. The diagnosis was confirmed by sampling the fluid within the vein, which showed significant levels of pancreatic enzymes.

To investigate whether preoperative computed tomography (CT)-based tumor-portal/superior mesenteric vein (PV/SMV) contact angle and contact length predict pathological venous invasion and refine prognostic stratification in anatomically resectable pancreatic ductal adenocarcinoma (R-PDAC). We retrospectively reviewed 108 patients who underwent upfront pancreaticoduodenectomy without neoadjuvant chemotherapy for pancreatic head PDAC, including 101 anatomically resectable cases and 7 borderline resectable cases with PV involvement (BR-PV). Tumor-PV/SMV contact angle and contact length were measured on multidetector CT. Their associations with pathological PV/SMV invasion, PV/SMV resection, and overall survival (OS) were analyzed. Both contact angle and contact length predicted pathological venous invasion, with optimal cutoff values of 90&#xb0; for angle (AUC&#x2009;=&#x2009;0.86) and 15&#xa0;mm for length (AUC&#x2009;=&#x2009;0.84), and both were significantly associated with pathological venous invasion and PV/SMV resection (all p&#x2009;<&#x2009;0.001). In the subgroup with R-PDAC, however, only contact length provided meaningful prognostic stratification. Patients with contact length&#x2009;&#x2265;&#x2009;15&#xa0;mm had significantly worse OS than those with contact length&#x2009;<&#x2009;15&#xa0;mm (p&#x2009;=&#x2009;0.0032) or no contact (p&#x2009;<&#x2009;0.001), and their survival was comparable to that of BR-PV patients (p&#x2009;=&#x2009;0.8548). In multivariable analysis, contact length&#x2009;&#x2265;&#x2009;15&#xa0;mm remained an independent adverse prognostic factor (HR 2.79, 95% CI 1.64-4.73, p&#x2009;<&#x2009;0.001). Preoperative CT-based assessment of tumor-PV/SMV contact length may serve as a practical marker for identifying a high-risk subgroup within R-PDAC and may help refine selection of patients for neoadjuvant treatment.

Robot-assisted pancreatoduodenectomy (RPD) is increasingly performed for cancer in the pancreatic head. Randomised evidence confirming its oncological safety and efficacy is lacking. The DIPLOMA-2x2 trial aims to compare the oncological safety of RPD versus OPD in terms of radicality (microscopically radical resection [R0] resection). We hypothesise that RPD is non-inferior to OPD in terms of radicality and superior regarding time to functional recovery. The DIPLOMA-2x2 trial is an investigator-initiated, international, multicentre, patient- and assessor-blinded randomised non-inferiority trial. The trial was conducted as a roll-over of the DIPLOMA-2 trial and includes 20 high-volume tertiary referral hospitals in 7 countries. Minimum surgeon's experience is 60 RPD and 60 OPD, with a minimum annual centre volume of 30 RPD prior to trial initiation. Eligible patients are adults (&#x2265;18&#xa0;years) with suspected or proven upfront resectable pancreatic ductal adenocarcinoma (PDAC) and distal cholangiocarcinoma (DCC) without any vascular involvement. Participants are randomised in a 2:1 ratio to RPD or OPD, respectively, stratified by tumour indication (proven PDAC versus other) and preoperative pancreatic fistula risk (high versus low). In total, 413 patients will be included, of which 137 previously randomised in DIPLOMA-2 and 276 newly recruited in DIPLOMA-2x2. Patients are blinded up to postoperative day 5. Primary outcome is pathological R0-resection rate (pR0; >1&#xa0;mm tumour clearance at surgical resection margins and anatomical surfaces, 0&#xa0;mm clearance at anterior surface), tested for non-inferiority with a -7% margin. Pathological assessment is blinded, and a randomly selected 10% of specimen will undergo central review. The key secondary outcome, tested for superiority, is time to functional recovery. Other secondary outcomes include lymph node retrieval, initiation/completion of adjuvant therapy, time to start of adjuvant therapy, disease-free and overall survival, quality of life, and cost-effectiveness. Safety outcomes include major complications (Clavien-Dindo grade&#x2009;&#x2265;&#x2009;III), serious adverse events, and 90-day mortality. Primary analyses will be based on the modified intention-to-treat principle, including all patients who underwent resection. Postoperative follow-up is up to 90&#xa0;days for short-term outcomes and up to 60&#xa0;months for survival. The DIPLOMA-2x2 trial evaluates whether RPD is oncologically safe compared to OPD in patients with upfront resectable PDAC and DCC in experienced high-volume centres. ISRCTN27483786. Registered: January 11, 2021 (updated: February 6, 2025). First enrolment: January 3, 2021. Expected completion of enrolment: May 2026.

The biological heterogeneity and oncological impact of R1 carcinoma in situ (R1cis) lesions in distal cholangiocarcinoma (DCC) remain unclear. This retrospective study evaluated the clinical significance of R1cis in patients with DCC undergoing pancreaticoduodenectomy (PD). We retrospectively analyzed 151 patients who underwent PD for DCC between 2005 and 2023, excluding those with in-hospital mortality or distant metastasis. Based on the final pathological diagnosis, patients were classified into three groups: final R0, final R1cis, and final R1inv (invasive carcinoma). Fourteen patients (9%) had final R1cis and seven (5%) had final R1inv. The final R1cis group showed significantly worse overall survival (OS) than the final R0 group (median survival time: 34.3 vs. 114.7 months, p&#x202f;=&#x202f;0.002). Preoperative and intraoperative analysis identified elevated preoperative CA19-9 (p&#x202f;<&#x202f;0.001), preoperative modified Glasgow Prognostic Score (p&#x202f;=&#x202f;0.038), and initial R1inv (p&#x202f;<&#x202f;0.001) as independent predictors of poor OS. Postoperative analysis demonstrated that pancreatic invasion (p&#x202f;=&#x202f;0.037), pT3/T4 (p&#x202f;=&#x202f;0.023), final R1cis (p&#x202f;=&#x202f;0.007), and final R1inv (p&#x202f;=&#x202f;0.001) were independent prognostic factors. Recurrence occurred more frequently in the R1cis/R1inv group, with increased rates of both local and distant recurrence. Final R1cis is an independent prognostic factor for poor survival in DCC after PD, highlighting the importance of achieving final R0 resection.

Intrapancreatic fat deposition (IPFD) has garnered appreciable attention across diverse medical disciplines amid the rising global burden of pancreatitis, pancreatic cancer and type 2 diabetes mellitus. Despite growing interest in the field, there remains no conceptual framework for it. To address this gap, 25 experts from 6 continents were brought together to develop guidance. Drawing on multiple peer-reviewed systematic reviews and applying an iterative, anonymous Delphi process, a consensus document was developed and ratified in Melbourne, Australia. The final document contains 58 recommendations - 30 reached unanimous agreement and 28 attained 90-99% agreement. The consensus formally defines fatty pancreas disorder (FPD) as a distinct pathological state, characterized by excessive IPFD that poses a risk to health. Assessment of IPFD is best performed with MRI. Expert-established diagnostic criteria enable identification and classification of FPD. Recognition of type 1 FPD (in individuals without excess body fat mass) and type 2 FPD (in individuals with excess body fat mass) is instrumental in gaining novel insights and tailoring preventive strategies to the individual. The Melbourne consensus is foundational in operationalizing the dissemination of new knowledge in the field, fostering intercontinental collaborations and, ultimately, addressing the global burden of diseases of the pancreas.

Pancreatic ductal adenocarcinoma (PDAC) is largely refractory to immune checkpoint blockade, owing to its immunosuppressive tumour microenvironment. Neutrophil extracellular traps (NETs) accumulate in PDAC and correlate with disease progression, yet whether NETs reprogram cancer-associated fibroblast (CAF) heterogeneity and the upstream tumour-intrinsic signals that sustain pathological NETosis remain undefined. To delineate how NETs instruct CAF subtype specification and immunosuppression in PDAC, identify upstream NETosis drivers and evaluate combinatorial therapeutic strategies targeting this axis. Quantitative spatial analysis of human PDAC specimens, NETs-pancreatic stellate cell and patient-derived CAF cocultures, biotinylated DNA pull-down with liquid chromatography-tandem mass spectrometry, live-cell integrin-blocking assays, Cleavage Under Targets and Release Using Nuclease (CUT&RUN) sequencing, orthotopic and hepatic colonisation models, CD8+ T-cell functional assays and single-cell RNA sequencing of an eight-arm therapeutic study were employed. NETs-DNA directly engaged integrin &#x3b1;5&#x3b2;1 (ITGA5) on fibroblasts via its N-terminal domain, initiating a FAK (focal adhesion kinase)/SRC (Src family tyrosine kinase)-YAP (Yes-associated protein)-IL-6 (interleukin-6)-JAK (Janus kinase)/STAT3 (signal transducer and activator of transcription 3) autocrine cascade specifying inflammatory CAF (iCAF) differentiation. Tumour-derived neutrophil gelatinase-associated lipocalin (NGAL), induced by IL-17, drove extracellular signal-regulated kinase (ERK)-reactive oxygen species-mediated NETosis. NETs-reprogrammed iCAFs accelerated tumour growth, hepatic colonisation and CD8+ T-cell exhaustion, with exhausted T cells spatially enriched in iCAF-rich regions. A composite NETs/ITGA5 signature stratified overall survival in patients with PDAC. Single-cell transcriptomics demonstrated that triple therapy (anti-IL-17+AV3+anti-PD-1) shifted fibroblasts from iCAF towards myofibroblastic CAF dominance, restored CD8+ T-cell effector programmes and achieved the greatest tumour suppression and survival benefit. We define an IL-17/NGAL/NETs/ITGA5 axis linking neutrophil-derived extracellular DNA to iCAF specification and immunosuppression in PDAC. Cotargeting IL-17 and ITGA5 synergises with PD-1 blockade, providing a rationale for combinatorial immunotherapy.

Pancreatic ductal adenocarcinoma (PDAC) remains a therapeutic challenge due to its dense stroma and lack of druggable targets. Through integrated bioinformatics analysis of in-house and public datasets, we systematically identified miR-21 as the most significantly upregulated oncomiR in PDAC, showing strong correlation with poor patient prognosis. RNA-targeted degradation has emerged as a promising strategy for cancer treatment, enabling precise disruption of oncogenic signaling by degrading disease-driving non-coding RNAs. Nevertheless, poor tissue penetration and insufficient tumor specificity limit its therapeutic potential in pancreatic cancer, owing to the dense fibrotic stroma and heterogeneous target expression. Herein, we developed a dual-targeting, bioresponsive Nb-RIBOTAC (Nb-Fc-Val-Cit-RIBOTAC), engineered by conjugating a cathepsin B-responsive linker to bridge an EGFR-targeting nanobody (Nb-Fc fusion) with a miR-21-specific RIBOTAC module. This rationally designed therapeutic achieved potent and selective miR-21 degradation in orthotopic PDAC models, with 60% target knockdown while completely sparing normal tissues, leading to significant tumor growth inhibition. Our study establishes a transformative paradigm bridging bioinformatic identification with precision RNA degradation technology, offering new therapeutic possibilities for PDAC treatment. The target selection strategy and modular design principles described herein may be broadly applicable to other challenging malignancies.

Serum Ca 19-9 is the most widely used biomarker in pancreatic ductal adenocarcinoma (PDAC). This study assessed the link between preoperative Ca 19-9, neoadjuvant chemotherapy (ChTNeo), and outcomes after pancreatic resection. We retrospectively analyzed 378 patients with PDAC who underwent resection. Patients were grouped by preoperative Ca 19-9: elevated (>37&#x2009;U/mL; N&#x2009;=&#x2009;320) or normal (&#x2264;37&#x2009;U/mL; N&#x2009;=&#x2009;58). ChTNeo was administered to 99 patients (30.9%) in the elevated group and 35 (60.3%) in the normal group. Local recurrence, distant metastases, and mortality were significantly more frequent in patients with elevated Ca 19-9, while progression-free and overall survival were shorter. Patients with normal Ca 19-9 had excellent outcomes regardless of ChTNeo. Patients with elevated preoperative Ca 19-9 and ChTNeo administration had significantly better outcomes than those undergoing upfront surgery. Normal preoperative Ca 19-9 identifies a group with a favorable prognosis after PDAC resection. Elevated preoperative Ca 19-9 is associated with worse oncological outcomes. Among these patients, ChTNeo was associated with better treatment outcomes than upfront surgery; however, because baseline Ca 19-9 levels before ChTNeo were unavailable, these findings should not be interpreted as evidence that elevated baseline Ca 19-9 predicts benefit from neoadjuvant chemotherapy.

Nanoliposomal irinotecan (nal-IRI) has become an established therapy for advanced pancreatic ductal adenocarcinoma (PDAC), both in the post-gemcitabine setting and, more recently, in the first-line NALIRIFOX regimen. Concerns remain regarding cross-resistance in patients previously exposed to conventional irinotecan. We performed a systematic review and meta-analysis to evaluate the impact of prior irinotecan exposure on outcomes with nal-IRI. We conducted a systematic literature search of PubMed, Embase, and the Cochrane Library through July 2025 following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Eligible studies included patients with advanced PDAC treated with nal-IRI-containing regimens and reported outcomes stratified by prior irinotecan exposure. Data extraction and risk of bias assessments were performed independently by two reviewers. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were pooled using random-effects models. Sensitivity and publication bias analyses were conducted. Thirteen retrospective studies comprising 2271 patients were included. One-third (33.1%) had received conventional irinotecan before nal-IRI. Prior irinotecan exposure was associated with inferior outcomes: pooled unadjusted and adjusted HRs for OS were 1.48 [95% confidence interval (CI) 1.24-1.76, P = 0.001] and 1.42 (95% CI 1.03-1.96, P = 0.030), respectively. For PFS, pooled unadjusted and adjusted HRs were 1.45 (95% CI 1.28-1.64, P < 0.001) and 1.72 (95% CI 1.16-2.54, P = 0.007), respectively. Patient-level subgroup analyses indicated that patients discontinuing prior irinotecan due to progression had significantly worse OS compared with those discontinuing for other reasons (HR 1.97, 95% CI 1.10-3.52). Most studies were high quality, and sensitivity analyses confirmed the robustness of the findings. Prior exposure to conventional irinotecan, particularly discontinuation for progression, reduced clinical benefit from subsequent nal-IRI therapy in advanced PDAC in observational cohorts. These findings support caution when considering nal-IRI soon after irinotecan progression and highlight the need for prospective sequencing studies.

The proportion of elderly patients with pancreatic ductal adenocarcinoma (PDAC) is increasing. This study aimed to investigate whether neoadjuvant treatment (NAT) and adjuvant therapy (AT) are effective in PDAC patients over 80&#xa0;years of age. Patients over 80&#xa0;years of age who underwent pancreatectomy for PDAC in 2012-2020 and were recorded in the Japan Society for Gastroenterological Surgery and Japan Pancreas Society databases were included. Propensity score matching (PSM) analysis was performed to determine whether NAT and AT contribute to survival. In patients treated from 2017 onward, resectability status was incorporated into the PSM model. Of the 3438 patients in the study population, the primary resectability-adjusted PSM analysis of NAT among patients treated from 2017 onward compared 274 matched pairs. The MST was 30.5 (95% CI, 26.2-NA) and 29.0 (95% CI, 22.3-38.0) months in the NAT and non-NAT groups, respectively, with no significant difference (p&#x2009;=&#x2009;0.205 [stratified log-rank]). In a complementary full-cohort PSM analysis, 393 matched pairs were compared; the MST was 32.9 and 30.2&#xa0;months, respectively, with no significant difference. In a PSM-matched comparison of 1213 patients who received AT versus 1213 patients who did not, MST was longer in the former (30.7 [95% CI, 27.3-33.2] versus 23.7 [95% CI, 21.8-26.1] months, p&#x2009;<&#x2009;0.001 [stratified log-rank]). NAT did not show a statistically significant survival benefit in PDAC patients aged 80&#xa0;years or older, however, this finding should be interpreted with caution. In contrast, AT was associated with improved survival.

Although curative resection yields favorable outcomes for non-functional pancreatic neuroendocrine tumors (pNETs), postoperative recurrence remains a major concern. Existing studies have largely relied on postoperative pathological factors, while imaging characteristics have seldom been comprehensively integrated into recurrence prediction models. This study aimed to develop and validate an integrated model combining imaging and clinicopathological features to improve recurrence risk stratification. This multicenter retrospective cohort study included patients from three tertiary centers in China who underwent curative resection for non-functional, G1/G2 pNETs. Recurrence-related factors were identified using Fine-Gray competing risk regression. A weighted imaging invasiveness index was derived from six routine preoperative CT features, and an integrated prediction model combining imaging and clinicopathological variables was developed and validated. The training and validation cohorts comprised 310 and 70 patients, respectively. Multivariable Fine-Gray model analysis identified four independent predictors of recurrence: tumor size (sHR&#xa0;=&#xa0;1.111, 95% CI: 1.013-1.218, p&#xa0;=&#xa0;0.026), tumor grade (G2 vs G1) (sHR&#xa0;=&#xa0;2.809, 95% CI: 1.171-6.743, p&#xa0;=&#xa0;0.021), perineural invasion (sHR&#xa0;=&#xa0;2.715, 95% CI: 1.005-7.333, p&#xa0;=&#xa0;0.049), and imaging invasiveness index (sHR&#xa0;=&#xa0;1.996, 95% CI: 1.008-3.951, p&#xa0;=&#xa0;0.047). Incorporating the imaging index improved predictive performance at 24 and 36&#xa0;months in both cohorts, and a four-variable risk score stratified patients into distinct risk groups. The integrated model combining the imaging invasiveness index with clinicopathological factors may improve recurrence prediction and support individualized risk stratification in patients with resected non-functional G1/G2 pNETs, although further validation in larger external cohorts is warranted.

Advanced pancreatic ductal adenocarcinoma (PDAC) often progresses rapidly during chemotherapy despite initial assessments of stable disease or partial response by Response Evaluation Criteria in Solid Tumors (RECIST 1.1), underscoring the limitations of the current methods for predicting short-term progressive disease (PD). To address this, the study developed a spatiotemporal deep learning framework that integrates convolutional and long short-term memory (LSTM) neural networks to dynamically predict PD at the next follow-up visit using serial computed tomography (CT) scans and baseline clinical variables. The model was trained on a retrospective cohort of 243 patients (415 predicted events, defined as temporal sequences for the next follow-up PD prediction) and evaluated across internal, external, and prospective cohorts. The model achieved area under the curve (AUC) values of 0.77, 0.76, and 0.74, respectively. Performance remained robust across chemotherapy regimens (AG or Gemcitabine-based, FOLFIRINOX, and SOXIRI; AUC 0.68-0.79), PD subtypes (target lesion growth vs. new metastases; AUC 0.72&#xa0;vs. 0.77), and baseline disease stages (locally advanced vs. metastatic; AUC 0.85&#xa0;vs. 0.71). This framework enables the noninvasive, real-time prediction of imminent PD in advanced PDAC, facilitating timely treatment modification. Its validated generalizability and reliance on routine clinical data underscore its potential for seamless integration into chemotherapy management.

Dysregulated cellular protein metabolism is a key hallmark of pancreatic ductal adenocarcinoma (PDAC). However, much remains to be learned about how this process is regulated in cancerous cells. Here we investigated the role of two co-transcribed microRNA (miRNA) species, miR-15a/16, in regulating cellular protein translation, cell growth, metabolic processes, and clinical features in PDAC. Using cultured PDAC models, we show that overexpression of miR-15a/16 in cancerous cells slows proliferation and attenuates protein synthesis rates. Bioinformatics analysis reveals that these miRNAs target a broad suite of pathophysiological and metabolic pathways, including numerous genes in cancer- and protein-related processes. Finally, using publicly available patient data, we report that miR-15a/16 expression is lower in PDAC tumors and in patients with pancreatitis than in healthy controls, and that high expression of miR-15a/16 in tumors is associated with improved survival in patients. Our results indicate that miR-15a/16 act as regulators of protein metabolism in PDAC, with potential clinical implications for the management of this devastating disease.

Unresectable pancreatic cancer (PC) is characterized by a high prevalence of sarcopenia and cachexia, which negatively impact survival, treatment toxicity, and quality of life (QoL). Currently, evidence evaluating exercise programs in this vulnerable population is limited. This prospective, two-arm randomized controlled trial (RCT) will recruit patients with unresectable PC undergoing chemotherapy. Participants will be randomized (1:1) to an intervention group (hypertrophy-oriented resistance training twice weekly) or a control group (standard care). The primary outcome is the change in total lean body mass (assessed by DXA) at Week 12. Secondary outcomes include maximal strength, peak power, cardiorespiratory capacity, and patient-reported measures. The HY-PANC protocol presents a replicable resistance training intervention designed specifically for advanced PC. The protocol has been submitted for review and approval by the Clinical Research Ethics Committee of the University Hospital of Getafe and registered on ClinicalTrials.com (NCT07470268). &#xa9; 2026 The Author(s). Current Protocols published by Wiley Periodicals LLC.

Gastroduodenal artery (GDA) and pancreaticoduodenal artery (PDA) aneurysms are rare visceral artery aneurysms associated with a high risk of rupture and life-threatening hemorrhage irrespective of size. Prompt diagnosis and appropriate management are therefore critical. This study aimed to evaluate the clinical outcomes of endovascular treatment for GDA and PDA aneurysms. Retrospective study design. We retrospectively reviewed 15 consecutive patients who underwent endovascular treatment for GDA or PDA aneurysms at a single center between January 2014 and March 2025. Analyzed data included patient demographics, clinical presentation, aneurysm characteristics, technical success, post-procedural complications, and long-term outcomes. None of the patients had a history of pancreatitis, previous interventions, surgery, or trauma. Celiac artery (CA) stenosis was identified in 13 (86.6%) patients and superior mesenteric artery (SMA) stenosis in 1 (6.6%) patient; 1 (6.6%) patient had no stenosis of CA or SMA. Additionally, 10 (66.7%) patients were asymptomatic at diagnosis, whereas 5 (33.3%) patients presented with abdominal pain. Among the symptomatic patients, 2 patients were confirmed to have ruptured aneurysms. All patients underwent coil embolization; additional stent placement was performed in two patients-one in the CA and one in the SMA-to preserve arterial flow. The technical success rate was 100%, with no procedure-related complications. Over a mean follow-up of 27.5 months, no aneurysm recurrence or reperfusion was observed. Endovascular treatment for GDA and PDA aneurysms is effective and durable. Although CA or SMA stenosis is commonly observed, routine revascularization may not be necessary.

Pancreatic ductal adenocarcinoma remains a formidable clinical challenge, with a very poor survival rate. It is highly metastatic and quickly exhibits chemoresistance, both of which are mediated by interactions of the tumor cells with their microenvironment. Extracellular vesicles are key mediators by which tumor cells interact with their microenvironment. Here, we utilized a data-independent acquisition proteomics workflow to characterize the protein cargo of extracellular vesicles isolated from patient-derived primary cells and cell lines of varying aggressiveness. Mapping 1432 unique proteins with high reproducibility, we identified protein signatures that robustly discriminated between short-term and long-term survival phenotypes. While the data set was highly enriched for established exosomal markers, differential expression and PLS-DA modeling revealed that the most significant indicators of short survival (high aggressiveness) were ribosomal proteins. STRING analysis confirmed these as highly connected interactome hubs. These findings suggest that the differential loading of translational machinery into the extracellular space&#x2500;likely via microvesicles or coisolated nonvesicular particles&#x2500;contributes to poor prognosis, offering new insights into the systemic secretome of aggressive tumors.

Pancreatic ductal adenocarcinoma (PDAC) exhibits diverse phenotypes, including epithelial and mesenchymal characteristics, yet these features have not been effectively translated into clinical applications. Mucins are implicated in tumor progression and therapeutic resistance and are considered potential diagnostic and therapeutic targets. In this study, five epithelial and three mesenchymal PDAC cell lines were cultured under two-dimensional (2D) and three-dimensional (3D) conditions to investigate mucin expression. Proteomic analysis identified five mucins (MUC1, MUC4, MUC5B, MUC19, and MUC20) in 2D culture and eight (including MUC2, MUC5AC, and MUC13) in 3D culture. Candidate mucins were further validated by immunocytochemistry with H-score assessment. MUC1 was consistently expressed in all PDAC cell lines and showed marked upregulation in several lines under 3D culture. In mesenchymal PDAC cell lines, mucin expression was largely restricted to MUC1, whereas epithelial lines displayed broad 3D-induced reorganization. Notably, MUC5AC was absent in 2D culture but robustly induced in all epithelial PDAC cell lines under 3D conditions. Other mucins, including MUC2, MUC4, MUC5B, MUC13, MUC19, and MUC20, were variably upregulated, with epithelial lines demonstrating higher diversity and intensity of expression. These findings demonstrate that 3D culture effectively reveals the plasticity and heterogeneity of mucin expression in PDAC, highlighting its potential as a platform for biomarker discovery and the development of therapeutic strategies.