Pancreatic cancer is currently one of the most lethal diseases. In recent years, increasing evidence has shown that reprogrammed metabolism may play a critical role in the carcinogenesis, progression, treatment and prognosis of pancreatic cancer. Affected by internal or external factors, pancreatic cancer cells adopt extensively distinct metabolic processes to meet their demand for growth. Rewired glucose, amino acid and lipid metabolism and metabolic crosstalk within the tumor microenvironment contribute to unlimited pancreatic tumor progression. In addition, the metabolic reprogramming involved in pancreatic cancer resistance is also closely related to chemotherapy, radiotherapy and immunotherapy, and results in a poor prognosis. Reflective of the key role of metabolism, the number of preclinical and clinical trials about metabolism-targeted therapies for pancreatic cancer is increasing. The poor prognosis of pancreatic cancer patients might be largely improved after employing therapies that regulate metabolism. Thus, investigations of metabolism not only benefit the understanding of carcinogenesis and cancer progression but also provide new insights for treatments against pancreatic cancer.

Pancreatitis is a significant global health concern with rising incidence, complex management, and substantial mortality. This study aimed to assess global and regional trends in pancreatitis from 1990 to 2021 and project future trends to 2050 using data from the Global Burden of Disease (GBD) Study 2021. We analyzed GBD 2021 data to evaluate age-standardized incidence (ASIR), mortality (ASMR), and disability-adjusted life years (DALYs) rates of pancreatitis. Regional trends, gender disparities, and correlations with the Socio-demographic Index (SDI) were examined. Key risk factors, including alcohol consumption, smoking, and metabolic disorders such as hyperlipidemia, were extracted and evaluated. A Bayesian age-period-cohort model (BAPC) was used for future projections. From 1990 to 2021, global pancreatitis cases increased from 1.73 million to 2.75 million, representing a rise of 59%. Despite this, ASIR decreased slightly from 37.62 to 32.81 per 100,000, a 12.8% reduction. Deaths rose from 68,490 to 122,416, an increase of 78.7%, while ASMR decreased from 1.69 to 1.45 per 100,000, a reduction of 14.2%. DALYs increased from 2.58 million to 4.10 million (59%). Significant regional variations were found, with Eastern Europe showing the highest ASIR, ASMR, and DALY rates. Projections indicate continued declines in ASIR, ASMR, and DALYs through 2050. While global age-standardized rates of pancreatitis have declined, significant regional and socioeconomic disparities persist. Targeted prevention efforts, particularly in high-burden areas like Eastern Europe, and addressing modifiable risk factors such as alcohol use are crucial for reducing the future burden of pancreatitis.

The incidence and mortality rates of pancreatic cancer are rising globally. This study examines global and regional trends in pancreatic cancer incidence, Disability Adjusted Life Years (DALYs), and mortality from 1990 to 2021, utilizing data from the most recent Global Burden of Disease (GBD) 2021 database. Data were sourced from the GBD database over the period from 1990 to 2021. Age-standardized rates for incidence, DALYs, and mortality were calculated per 100,000 population. We also calculated the proportion of DALYs and mortality attributable to risk factors. The Bayesian age-period-cohort model was applied to project future trends until 2050. Between 1990 and 2021, the global incidence of pancreatic cancer increased significantly, with the number of cases rising from approximately 207,905 to 508,533 and the age-standardized incidence rate (ASIR) increasing from 5.47 to 5.96 per 100,000 population. The global burden of pancreatic cancer, measured in DALYs, rose from 5.21 million to 11.32 million. Mortality rates showed a similar upward trend, with the number of deaths increasing from around 211,613 to 505,752, and the age-standardized mortality rate (ASMR) rising from 5.655 to 5.948 per 100,000 population. Notable increases in ASIR and ASMR were observed in low-middle and low sociodemographic index regions with males experienced higher rates compared to females. Age-standardized DALYs rate (ASDR) and ASMR worldwide were attributable to tobacco smoking, high BMI, and high fasting plasma glucose. Furthermore, our projection model estimates that the ASIR and ASMR of pancreatic cancer will significantly decline, while the ASDR is anticipated to maintain a steady downward trend by 2050. This study offers a comprehensive analysis of pancreatic cancer trends, providing crucial insights for public health planning and policy-making. Addressing identified risk factors and targeting high-risk populations are essential for effective strategies to reduce the global burden of pancreatic cancer.

Background: The prognosis of pancreatic cancer patients remains relatively poor. Although some patients would receive surgical resection, distant metastasis frequently occurs within one year. Epithelial-mesenchymal transition (EMT), as a pathological mechanism in cancer progression, contributed to the local and distant metastasis of pancreatic cancer. Methods: Tissue microarray analysis and immunohistochemistry assays were used to compare the expression of EGR1 in pancreatic cancer and normal pancreatic tissues. Transwell chambers were used to evaluated the migration and invasion ability of cancer cells. Immunofluorescence was utilized to assess the expression of E-cadherin. ChIP-qPCR assay was applied to verify the combination of EGR1 and SNAI2 promoter sequences. Dual-luciferase reporter assay was used to detect the gene promoter activation. Co-IP assay was conducted to verify the interaction of EGR1 and p300/CBP. Results: EGR1 was highly expressed in pancreatic cancer rather than normal pancreatic tissues and correlated with poor prognosis and cancer metastasis. EGR1 was proved to enhance the migration and invasion ability of pancreatic cells. Besides, EGR1 was positively correlated with EMT process in pancreatic cancer, via a SNAI2-dependent pathway. P300/CBP was found to play an auxiliary role in the transcriptional activation of the SNAI2 gene by EGR1. Finally, in vivo experiments also proved that EGR1 promoted liver metastasis of pancreatic cancer. Conclusion: Our findings implied the EMT-promoting effect of EGR1 in pancreatic cancer and revealed the intrinsic mechanism. Blocking the expression of EGR1 may be a new anticancer strategy for pancreatic cancer. Graphical

Pancreatic cancer remains one of the most lethal diseases with a relatively low 5-year survival rate, and gemcitabine-based chemoresistance occurs constantly. Mitochondria, as the power factory in cancer cells, are involved in the process of chemoresistance. The dynamic balance of mitochondria is under the control of mitophagy. Stomatin-like protein 2 (STOML2) is located in the mitochondrial inner membrane and is highly expressed in cancer cells. In this study, using a tissue microarray (TMA), we found that high STOML2 expression was correlated with higher survival of patients with pancreatic cancer. Meanwhile, the proliferation and chemoresistance of pancreatic cancer cells could be retarded by STOML2. In addition, we found that STOML2 was positively related to mitochondrial mass and negatively related to mitophagy in pancreatic cancer cells. STOML2 stabilized PARL and further prevented gemcitabine-induced PINK1-dependent mitophagy. We also generated subcutaneous xenografts to verify the enhancement of gemcitabine therapy induced by STOML2. These findings suggested that STOML2 regulated the mitophagy process through the PARL/PINK1 pathway, thereby reducing the chemoresistance of pancreatic cancer. STOML2-overexpression targeted therapy might be helpful for gemcitabine sensitization in the future.

Background: Thyroid Hurthle cell carcinoma (HCC) is a rare disease with high risk of invasion and metastasis and poor prognosis. The clinical characteristics, prognosis and treatment of HCC are still controversial, and clinical data are still limited to some case reports. Therefore, understanding the characteristics and survival factors of HCC is clinically necessary. Methods: This study collected data from HCC patients diagnosed pathologically from 2004 to 2015, including basic population characteristics, tumor characteristics, and epidemiological and survival data. The data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database to conduct a population cohort study. Results: A total of 2101 HCC patients with an average age of 55.42 ± 15.27 years were enrolled in this study. Of them, 1740 (82.82%) patients had local disease, 245 (11.66%) had regional disease, and 89 (4.24%) had distant disease. Total thyroidectomy was performed in 1669 (79.44%) patients, partial thyroidectomy was performed in 382 (18.18%) patients, and radioactive iodine (RAI) was used in 1155 (54.97%) patients. The 5-year and 10-year cancer-specific survival rate was 95.4 and 92.6%, respectively. The distant disease group had significantly more male patients, multifocal tumors, and extensive tumors compared to the local disease group. Multivariate survival analysis showed that age (P < 0.05), SEER stage (P < 0.001), and T-stage (P = 0.001) had significant effects on survival. There was no significant difference in survival between total and partial thyroidectomy (P = 0.078), or between RAI and non-RAI (P = 0.733). Conclusion: Male gender, multifocal tumors, and extended tumors are associated with increased risk of late stage HCC. Age over 45 years, distant SEER stage, and late T-stage are independent risk factors for mortality in HCC.