The association between Life's Essential 8 and all-cause, cancer and non-cancer mortality in US Cancer Survivors: A retrospective cohort study of NHANES.

OBJECTIVE: To investigate Life's Essential 8 (LE8), a measure of cardiovascular health (CVH), associations with mortality outcomes in cancer survivors. METHODS: A prospective cohort study included 1818 cancer survivors aged ≥20 years (weighted population: 13,204,583) from National Health and Nutrition Examination Survey (NHANES) 2005-2018. Linked to mortality data through 2019, LE8 data were gathered through self-reports and lab tests. An LE8 score of 80-100 is considered high CVH, 60-79 is moderate CVH, and 0-59 is low CVH. Multivariable Cox proportional hazards regression models were employed to evaluate the associations between LE8 and all-cause, cancer-specific and non-cancer mortality. Subsequently, subgroup analyses were conducted to assess the relationship between LE8 and mortality rates across various subgroups. RESULTS: At baseline, there were 1818 cancer survivors. In a 15-year follow-up, 2548 deaths occurred: 601 from cancer, 647 from heart disease, and 1300 from other causes. Multivariable models showed high CVH associated with lower hazard ratios for all-cause, cancer-specific and non-cancer mortality vs. low CVH. Cumulative mortality rates increased during follow-up, more so in the low CVH group. Subgroup analysis revealed significant LE8 interactions with age or Poverty Income Ratio (PIR) for all-cause mortality. Additionally, significant interactions between LE8 and PIR were identified for cancer-specific and non-cancer mortality risks (P for interaction <0.05). CONCLUSION: Among U.S. cancer survivors, higher CVH is independently linked to lower all-cause, cancer-specific, and non-cancer mortality risks. The new CVH definition shows promise as a primary prevention strategy to reduce mortality rates in U.S. cancer survivors.

Neutrophil extracellular traps regulating tumorimmunity in hepatocellular carcinoma.

As a component of the innate immune system, there is emerging evidence to suggest that neutrophils may play a critical role in the initiation and progression of hepatocellular carcinoma (HCC). Neutrophil extracellular traps (NETs) are web-like chromatin structures that protrude from the membranes during neutrophil activation. Recent research has shown that NETs, which are at the forefront of the renewed interest in neutrophil studies, are increasingly intertwined with HCC. By exploring the mechanisms of NETs in HCC, we aim to improve our understanding of the role of NETs and gain deeper insights into neutrophil biology. Therefore, this article provides a summary of key findings and discusses the emerging field of NETs in HCC.

A risk signature based on endoplasmic reticulum stress-associated genes predicts prognosis and immunity in pancreatic cancer.

Introduction: The involvement of endoplasmic reticulum (ER) stress in cancer biology is increasingly recognized, yet its role in pancreatic cancer (PC) remains unclear. This study aims to elucidate the impact of ER stress on prognosis and biological characteristics in PC patients. Methods: A bioinformatic analysis was conducted using RNA-seq data and clinicopathological information from PC patients in the TCGA and ICGC databases. The ER stress-associated gene sets were extracted from MSigDB. ER stress-associated genes closely linked with overall survival (OS) of PC patients were identified via log-rank test and univariate Cox analysis, and further narrowed by LASSO method. A risk signature associated with ER stress was formulated using multivariate Cox regression and assessed through Kaplan-Meier curves, receiver operating characteristic (ROC) analyses, and Harrell's concordance index. External validation was performed with the ICGC cohort. The single-sample gene-set enrichment analysis (ssGSEA) algorithm appraised the immune cell infiltration landscape. Results: Worse OS in PC patients with high-risk signature score was observed. Multivariate analysis underscored our ER stress-associated signature as a valuable and independent predictor of prognosis. Importantly, these results based on TCGA were further validated in ICGC dataset. In addition, our risk signature was closely associated with homeostasis, protein secretion, and immune regulation in PC patients. In particular, PC microenvironment in the high-risk cluster exhibited a more immunosuppressive status. At last, we established a nomogram model by incorporating the risk signature and clinicopathological parameters, which behaves better in predicting prognosis of PC patients. Discussion: This comprehensive molecular analysis presents a new predictive model for the prognosis of PC patients, highlighting ER stress as a potential therapeutic target. Besides, the findings indicate that ER stress can have effect modulating PC immune responses.