Cancer Biology & Medicine最新文献

Objective: The key molecular events signifying the Helicobacter pylori-induced gastric carcinogenesis process are largely unknown.

Methods: Bulk tissue-proteomics profiling were leveraged across multi-stage gastric lesions from Linqu (n = 166) and Beijing sets (n = 99) and single-cell transcriptomic profiling (n = 18) to decipher key molecular signatures of H. pylori-related gastric lesion progression and gastric cancer (GC) development. The association of key proteins association with gastric lesion progression and GC development were prospectively studied building on follow-up of the Linqu set and UK Biobank (n = 48,529).

Results: Concordant proteomics signatures associated with H. pylori infection and gastric carcinogenesis (ρ = 0.784, correlation P = 1.80 × 10^-36) were identified. RNA expression of genes encoding 13 up- and 15 down-regulated key proteins displayed trending alterations in the transition from normal gastric epithelium to intestinal metaplasia, then to malignant cells. A 15-tissue protein panel integrating these signatures demonstrated potential for targeting individuals at high risk for progressing to gastric neoplasia (OR = 7.22, 95% CI: 1.31-39.72 for the high-score group). A 4-circulating protein panel may be used as non-invasive markers predicting the risk of GC development (hazard ratio = 3.73, 95% confidence interval: 1.63-8.54, high-risk vs. low-risk populations, area under the curve = 0.75).

Conclusions: Concordant proteomics signatures associated with H. pylori infection and gastric carcinogenesis were unveiled with potential as biomarkers for targeted prevention strategies.

Prostate cancer is a significant global health issue with inflammation emerging as a critical driver of progression. The prostate tumor microenvironment (TME) is comprised of tumor cells, mesenchymal stem cells, immune cells, cancer-associated fibroblasts, adipocytes, and the extracellular matrix. All of these TME components interact via soluble factors, such as growth factors, cytokines, and chemokines. These interactions remodel the TME and drive inflammation and tumor progression. Prolonged inflammation leads to dysregulated activation and infiltration of immune cells in the TME. This process maintains an immunosuppressive environment and facilitates epithelial-to-mesenchymal transition, migration, and invasion. Chronic inflammation causes inflammatory mediators to enter the circulation over time, as evidenced by systemic biomarkers, such as the systemic immune-inflammation index, which links inflammation to disease severity. Interactions between the prostate gland and adipose tissues further exacerbate systemic inflammation. Inflammation in the prostate gland confers resistance to therapy, primes distant metastatic niches, and promotes metastatic spread, resulting in poor clinical outcomes. Therapeutic strategies, such as anti-inflammatory agents and immunotherapies, hold promise in mitigating disease burden. This review explored the immune landscape of systemic inflammation in prostate cancer, discussed the role of the immune landscape in resistance to therapy and metastasis, and offered insights into potential interventions for targeting inflammation to limit prostate cancer burden.

Objective: This study aimed to assess the global, regional, and national burden of early-onset gastric cancer (EOGC) and the attributable risk factors from 1990-2021 with projections extending to 2040.

Methods: The EOGC burden was quantified using incidence, prevalence, mortality, and disability-adjusted life years (DALYs) with calculation of age-standardized rates. The risk factor contributions were analyzed and disparities were evaluated using the slope index of inequality. Future trends for 2021-2040 were estimated using a Bayesian age-period-cohort model.

Results: There were approximately 125,000 new cases of EOGC globally in 2021 with an estimated 336,000 individuals living with EOGC and 78,000 associated deaths, contributing to 3.86 million DALYs. The highest EOGC incidence rates existed among individuals 45-49 years of age. The global age-standardized incidence, prevalence, mortality, and DALY rates demonstrated an overall decline between 1990 and 2021. Smoking and high-salt dietary intake were the leading risk factors for DALYs with regional and gender-based variations. Smoking accounted for > 10% of DALYs in Central Europe and East Asia, while high-salt dietary intake accounted for approximately 8% of DALYs. Despite the overall decline in the EOGC burden, disparities across geographic regions widened. Projections indicated a continued gradual reduction in EOGC burden through 2040.

Conclusions: Although the global burden of EOGC has decreased, significant disparities persist across geographic regions, age groups, and genders. Public health interventions should combine smoking prevention strategies (e.g., youth education and tobacco taxation) with cessation programs with dietary salt reduction initiatives.

Objective: This study aimed to analyze the temporal trends in cancer mortality in China from 2013-2021 and project the future trends through 2030.

Methods: This study was based on the China Causes of Death Surveillance Dataset, which covers 2.37 billion person-years. Age-standardized mortality rates (ASMRs) were calculated using Segi's world standard population and the trends were evaluated via Joinpoint regression. Bayesian age-period-cohort models were used for mortality projections. Contributions of demographic changes (population size and age structure) and risk factors to the mortality burden were quantified using the decomposition analysis.

Results: The combined ASMRs for all cancers decreased annually by 2.3%, driven by significant declines in esophageal (4.8%), stomach (4.5%), and liver cancers (2.7%). In contrast, the pancreatic and prostate cancer ASMRs increased by 2.0% and 3.4% annually, respectively. Urban areas demonstrated a more rapid decline in the combined ASMRs for all cancers [average annual percent change (AAPC) = -3.0% in urban areas vs. -2.0% in rural areas], highlighting persistent disparities. Population aging contributed 20%-50% to death increases between 2013 and 2021. The combined ASMRs for all cancers, like the findings of temporal trend analyses, will continue to decrease and the regional (urban and rural) difference is projected to simulate that of the temporal trend through 2030. In fact, cancer deaths are projected to reach 2.4 million by 2030.

Conclusions: The cancer burden in China is facing the dual challenges of population aging and urban-rural disparities. It is necessary to prioritize rural screening, control risk factors, such as smoking and diet, and integrate more efficacious cancer prevention and control programmes into the policy to reduce mortality in the future.

The tumor immune microenvironment (TIME) represents a complex battlefield where metabolic competition and immune evasion mechanisms converge to drive cancer progression. Amino acids, with their multifaceted biological roles, have emerged as pivotal regulators of tumor cell proliferation and immune cell functionality. The sensing mechanisms by which amino acids within the tumor microenvironment influence cellular growth, survival, and immune function are systematically explored in this review; the latest advances in understanding amino acid metabolism in tumor biology are also reviewed. In addition, the multifaceted roles of key amino acids in shaping the TIME with particular emphasis on tumor immunity and malignant growth were investigated. Finally, emerging therapeutic strategies targeting amino acid metabolism to reprogram the TIME are discussed, highlighting promising approaches, such as CAR-T cell therapy and engineered bacterial interventions. Through this comprehensive analysis, critical insights into future research directions and potential clinical translation of amino acid-targeted interventions are provided.