The disease burden of pancreatic cancer in East Asia is at a high level, but the epidemiological characteristics of pancreatic cancer in the region have not been systematically studied. Joinpoint analysis was used to identify average annual percentage change (AAPC) and annual percentage change (APC) in mortality. Age-period-cohort models were used to analyze age-period cohort effects across countries. Bayesian age-period-cohort (BAPC) analysis was used to project the burden of disease for 2020-2030. Pancreatic cancer mortality in males in Japan (2012-2019, APC = −0.97) and Korea (2012-2019, APC = −0.91) has shown a decreasing trend since 2012 (P < .05). However, China (2016-2019, APC = 3.21), Mongolia (2015-2.019, APC = 2.37), and North Korea (2012-2019, APC = 0.47) showed a significant increase in pancreatic cancer in both genders (P < .05). Risk factors for pancreatic cancer in East Asia remained largely stable between 2010 and 2019. Mortality of pancreatic cancer due to smoking began to decline in areas with high socio-demographic index (SDI), and mortality of pancreatic cancer due to high body mass index and high fasting plasma glucose increased with SDI. The age-standardized mortality for pancreatic cancer in Chinese males is expected to exceed that of Japan and South Korea by 2030, but the disease burden of pancreatic cancer in Japan and South Korea remains at extremely high levels. Economically developed countries are beginning to show a decreasing trend in the burden of pancreatic cancer disease, and developing countries are experiencing a rapid increase in the age-standardized death rate (ASDR) of pancreatic cancer.

Background: Progress in immunotherapy for pancreatic ductal adenocarcinoma (PDAC) has been slow, yet the relationship between microorganisms and metabolites is crucial to PDAC development. This study compares the biliary microbiota and metabolomic profiles of PDAC patients with those of benign pancreatic disease patients to investigate PDAC pathogenesis and its relationship with immunotherapy.Methods: A total of 27 patients were recruited, including 15 diagnosed with PDAC and 12 with benign pancreaticobiliary conditions, all of whom underwent surgical treatment. Intraoperative bile samples were collected and analyzed using 16S rRNA sequencing in conjunction with liquid chromatography-mass spectrometry (LC-MS). Multivariate statistical methods and correlation analyzes were employed to assess differences in microbial composition, structure, and function between malignant and benign pancreatic diseases. Additionally, a retrospective analysis was conducted on PDAC patients post-surgery regarding immunotherapy and its correlation with metabolic components.Results: PDAC patients exhibited a significantly higher abundance of bile microbiota compared to controls, with notable differences in microbiota structure between the two groups (P < 0.05). At the genus level, Muribaculum was markedly enriched in the bile of PDAC patients and was strongly correlated with phosphatidic acid (PA) (10:0/a-17:0). Both of these components, along with the tumor marker CA199, formulated a predictor of PDAC. Furthermore, PA (10:0/a-17:0) demonstrated a strong correlation with PDAC immunotherapy outcomes (Rho: 0.758; P=0.011).Conclusion: These findings suggest that the biliary microbiota and associated metabolites play a crucial role in the development of PDAC and may serve as potential predictive biomarkers and therapeutic targets for disease management.

Background: To evaluate temporal trends, associated risk factors, and cross-national inequalities in the distribution of pancreatic cancer from 1990 to 2021. Methods: Temporal trends were measured using the average annual percent change and annual percent change. A comparative risk assessment framework was employed to estimate the proportion of disability-adjusted life years (DALYs) attributable to specific risk factors for pancreatic cancer. In addition, the unequal distribution of the global burden of pancreatic cancer was quantified using the inequality slope index and the concentration index, as recommended by the World Health Organization. Results: From 1990 to 2021, the global incidence, prevalence, mortality and DALYs associated with pancreatic cancer have increased in absolute numbers. At the regional level, Central Asia recorded the highest values for all four indicators, while Western Sub-Saharan Africa experienced the most pronounced escalation in disease burden. Notably, the burden of pancreatic cancer was consistently higher in males than in females throughout the study period. Cross-national inequalities analysis reveals that disparities in pancreatic cancer burden are concentrated in countries with relatively higher socio-demographic index. To date, the high fasting plasma glucose remained the major risk factor that influenced the DALYs of pancreatic cancer, followed by smoking and high body mass index. Conclusion: The global burden of pancreatic cancer is rising, particularly among males and in high-income regions. This trend highlights the urgent need for targeted prevention strategies and improved management of modifiable risk factors, with a specific focus on these high-risk populations.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death, with limited treatment options and high recurrence rates. Prognostic biomarkers and predictors of immune checkpoint inhibitor (ICI) response are urgently needed. This study aimed to develop a macrophage-related gene signature to predict patient outcomes and ICI efficacy, with a focus on the functional role of PLAUR. Single-cell RNA sequencing of paired HCC and normal liver tissues was used to identify macrophage subtypes. A prognostic gene signature was constructed based on macrophage-related genes and validated using the TCGA-LIHC cohort. TIDE analysis was performed to assess ICI response prediction. PLAUR-related cell communication was evaluated using CellChat. Functional assays were conducted to assess the effect of PLAUR knockdown on macrophage polarization, tumor cell behavior, and PI3K/AKT/mTOR pathway activity. Tissue microarray immunofluorescence validated PLAUR expression in situ. An eight-gene macrophage-related signature showed strong prognostic and predictive value. High-risk patients had poorer survival and reduced ICI responsiveness. PLAUR was overexpressed in tumor-associated macrophages and correlated with enhanced cell communication in tumors. Knockdown of PLAUR inhibited M2 polarization, reduced tumor cell proliferation and migration, and suppressed PI3K/AKT/mTOR signaling. In vivo, PLAUR silencing significantly reduced tumor growth in a THP-1/SKHep1 co-injection model. We identified a novel macrophage-related gene signature with clinical utility in HCC. PLAUR promotes immunosuppressive polarization and tumor progression via the PI3K/AKT/mTOR pathway, representing a potential therapeutic target and biomarker for immunotherapy response.