Explore the vast range of titles available.

The morbidity and mortality rates of head and neck squamous cell carcinoma (HNSCC) remain high worldwide. Therefore, there is an urgent need to identify a new prognostic biomarker to guide the personalized treatment of HNSCC patients. Increasing evidence suggests that circadian rhythm genes play an important role in the development and progression of cancer. We aimed to explore the value of circadian rhythm genes in predicting prognosis and guiding the treatment of HNSCC. We first obtained a list of circadian rhythm genes from previous research. The sequencing data were retrieved from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Finally, univariate Cox proportional hazard analysis, least absolute shrinkage and selection operator (LASSO) regression, and multivariate Cox proportional hazard analysis were performed to develop a prognostic signature (Circadian Rhythm-Related Gene Prognostic Index, CRRGPI) consisting of nine circadian rhythm genes. The signature exhibited good performance in predicting overall survival. Patients with low CRRGPI scores had lower metabolic activities and an active antitumour immunity ability. Additionally, a clinical cohort was used to further evaluate the ability of the CRRGPI to predict the efficacy of immune checkpoint inhibitors. In conclusion, the novel circadian rhythm-related gene signature can provide a precise prognostic evaluation with the potential capacity to guide individualized treatment regimens for HNSCC patients.

Background The etiological composition and disease burden of hepatocellular carcinoma (HCC) in Cambodia show significant dynamic changes, and targeted prevention and control strategies are urgently needed. Methods First, this study obtained data on HCC by age, sex, etiology, incidence, prevalence, deaths, disability-adjusted life years (DALYs), and attributable risk from the 2021 GBD study focused on Cambodia data from 1990 to 2021. Secondly, the study also examined the temporal trend of subtype-specific HCC disease burden in Cambodia from 1990 to 2021 using linear regression modeling to calculate estimated annual percentage change (EAPC) values. Finally, risk factors for HCC of different etiologies were also analyzed. Results Although the age-standardized rate (ASR) of HBV, HCV and NAFLD-related HCC showed a downward trend, the total number of cases and the number of deaths continued to increase. The ASR of HCC related to alcoholic liver disease rose against the trend. The burden of HBV and HCC related to alcoholic liver disease is significantly heavier in men, while the burden of HCC related to HCV and NAFLD is more severe in women. Viral hepatitis (HBV/HCV) remains the main cause of liver cancer in Cambodia, but the contribution of metabolic causes (NAFLD) continues to rise. Conclusion HCC poses a significant threat to the health of Cambodians. This study provides key data support for Cambodia to formulate a comprehensive prevention and control strategy for HCC that is “virus control - metabolic intervention - gender stratification”.

Immune cells play complex roles in the formation of keloid. We aimed to investigate the causal relationship between immune cells and keloid and provide genetic evidence for the association between immune cells and keloid risk. Based on data from a genome-wide association study (GWAS), we performed a comprehensive two-sample Mendelian randomization (MR) analysis of 731 immune cell traits in 481,912 keloid cases. We used the inverse-variance weighting (IVW) method as the primary analysis. Then, a comprehensive sensitivity analysis was adopted to verify the results’ robustness, heterogeneity, and horizontal pleiotropy. Finally, reverse MR analysis was performed. The IVW method in forward MR analysis showed that CD66b++ myeloid cell AC was negatively associated with keloid risk (OR<1, p<0.05). Consistently, reverse MR analysis showed that keloid risk was negatively associated with CD66b++ myeloid cell AC (OR=0.85, p=0.012). No significant horizontal pleiotropy or heterogeneity was observed. The results of MR analysis demonstrate a bidirectional causal association between CD66b++ myeloid cell AC and keloid formation, suggesting that CD66b++ myeloid cell AC is a protective factor against keloid.

Background Metabolic dysregulation is increasingly implicated in tumorigenesis, but the metabolic profile of colorectal cancer (CRC) has not been fully elucidated. This study investigates the potential causal role of specific circulating metabolites in CRC development by integrating genetic instrumental variable analysis with biological validation in vitro. Methods We conducted a two-sample Mendelian randomization (MR) analysis using publicly available genome-wide association study (GWAS) datasets comprising 1,400 metabolites. Causal effects were estimated using the inverse variance weighted method and the weighted median approach. Heterogeneity and pleiotropy were evaluated to ensure robustness. Metabolites with consistent associations were subsequently investigated in CRC cell models to determine their functional effects. Results Fifty-eight metabolites demonstrated potential causal links with CRC. Among them, cytosine was identified as a risk-enhancing metabolite (OR = 1.166, 95% CI = 1.020–1.333, P  = 0.023), while piperine showed a protective effect (OR = 0.862, 95% CI = 0.768–0.967, P  = 0.011). Functional experiments confirmed that cytosine promoted CRC cell proliferation, while piperine inhibited tumor growth. Conclusion These findings suggest that specific circulating metabolites, such as cytosine and piperine, may influence colorectal cancer development through distinct biological mechanisms. Their involvement in metabolic pathways relevant to carcinogenesis merits further exploration, particularly regarding their potential translational applications.

Background The Filamin C (FLNC) gene, pivotal for cellular structure and function, holds significance in cancer biology. Methods We conducted a comprehensive study using various analytical approaches, including survival analysis, immune response assessment, methylation profiling, and single-cell analysis. Results Our findings indicate that abnormal FLNC expression correlates with unfavorable prognosis across multiple cancer types, suggesting its potential as a prognostic biomarker. FLNC dysfunction influences the tumor microenvironment, promoting immunosuppressive conditions and disease progression. Methylation profiling reveals a strong correlation between increased methylation, FLNC downregulation, and patient survival, highlighting the role of epigenetic regulation in cancer development. Single-cell analysis uncovers spatial and temporal variations in FLNC expression, identifying distinct cancer cell subsets with unique functional implications. Finally, immunohistochemistry was used to verify the results in different tumors. Conclusions In conclusion, our research provides insights into the versatile role of FLNC in cancer biology, emphasizing its clinical significance and potential applications as a diagnostic, prognostic, and therapeutic target across diverse cancer types. These findings offer valuable insights for personalized therapeutic interventions and precision medicine approaches.

Skin cancer (SC) is a significant public health issue, with increasing incidence rates globally. Although environmental factors such as ultraviolet (UV) exposure are recognized risk factors, the impact of metabolites on SC development has not been thoroughly examined. This study seeks to explore the causal association between metabolites and SC risks using a Mendelian randomization (MR) approach. Our analysis revealed a total of 76 metabolites associated with SC risk. Of them, leucine to N-palmitoyl-sphingosine ratio, glycerol to palmitoylcarnitine ratio, oleoyl-linoleoyl-glycerol levels, and hypotaurine-to-taurine ratio were strongly associated with SC. Notably, leucine to N-palmitoyl-sphingosine ratio and glycerol to palmitoylcarnitine ratio were linked to increased risk factors for SC. However, oleoyl-linoleoyl-glycerol levels and hypotaurine-to-taurine ratio served as the protective indicators of SC. This study highlights the potential role of metabolites in skin cancer etiology, suggesting that metabolic factors may serve as important targets for prevention and risk assessment strategies.

Hepatocellular carcinoma (HCC) is a complex and multifaceted disease that is increasingly prevalent globally. The involvement of immune cells in the tumour microenvironment has been linked to the progression of HCC, but the exact cause-and-effect relationship is not yet clear. In this study, we utilise Mendelian randomization (MR) to investigate the potential causal links between immune factors and the development of HCC. We executed a comprehensive MR study, leveraging publicly accessible genetic datasets to explore the potential causal links between 731 types of immune cells and HCC. Our analysis primarily applied inverse variance weighting and weighted median methods. To evaluate the robustness of our findings and probe for the presence of heterogeneity and pleiotropy, we also conducted thorough sensitivity analyses. We found 36 immune cells were associated with HCC, CD64 on CD14- CD16+ monocytes (OR = 1.328, 95% CI = 1.116- 1.581, = 0.001), CD3- lymphocyte %lymphocytes (OR = 1.341, 95% CI = 1.027- 1.750, p = 0.031), HLA DR on CD14+ monocytes (OR = 1.256, 95% CI = 1.089- 1.448, = 0.002), CD19 on CD19 on Plasma Blast-Plasma Cell (OR = 1.224, 95% CI = 1.073- 1.396, = 0.003), CCR2 on monocytes (OR = 1.204, 95% CI = 1.073- 1.351, = 0.002) and Naive CD4+ T cell Absolute Count (OR = 0.797, 95% CI = 0.655- 0.969, = 0.023) were the most strongly associated with HCC. Among them, CD64 on CD14- CD16+ monocytes, CD3 - lymphocyte %lymphocytes, HLA DR on CD14+ monocytes and CD19 on Plasma Blast-Plasma Cells are the risk factors, while Naive CD4+ T cell Absolute Count are protective factors for HCC. Our MR analysis of the role of immune cells and HCC provides a framework for knowledge of circulating immune status. Systematic assays of infiltrating immune cells in HCC can help dissect the immune status of HCC, assess the current use of checkpoint blockers, and most importantly, aid in the development of innovative immunotherapies. Further research is necessary to validate these findings and explore the underlying mechanisms that influence the immune response to HCC.

Background Pancreatic ductal adenocarcinoma (PDAC) is challenging to treat due to its immunosuppressive tumor microenvironment (TME) and resistance to immune checkpoint inhibitors. This study aims to discover new therapeutic targets and predictive biomarkers for PDAC. Methods Using Mendelian randomization, we studied causal relationships between PDAC and an array of immune cell traits, bacterial traits, inflammatory factors, and blood metabolites. We employed large genome-wide association study datasets and the two-sample MR approach for the investigation. Results Our results highlight suggestive evidence of associations between PDAC and distinct immune cell phenotypes, revealing nuanced alterations across monocytes, T-cells, B-cells, dendritic cells, and myeloid-derived suppressor cells. Our study provides a granular view of the PDAC-immune interface, identifying key immune cell traits and their associations with PDAC. For instance, our findings suggest a detrimental reduction in various monocyte traits, alongside a decrease in B-cell populations. Conversely, certain T-cell subsets showed increased associations, indicating potential targets for immunotherapeutic strategies. The bacterial trait associations, particularly with Collinsella and Ruminococcus torques, highlight the gut microbiome's influence on immune modulation and PDAC pathogenesis. Additionally, the traits concerning Interleukin-12 subunit beta levels and T-cell surface glycoprotein CD5 levels further indicate their function of this complex interaction. Conclusions This study enhances our understanding of PDAC's resistance to immunotherapies and highlights the potential of personalized immunotherapy and metabolic pathway modulation in PDAC treatment. Our findings provide supportive evidence for research and clinical translation.

Upper gastrointestinal (UGI) cancers, including esophageal (EC) and gastric (GC) cancers, pose a significant global health challenge. Previous studies have indicated a fundamental correlation between basophil count and the risk of UGI cancer. However, confirming a causal relationship demands further investigation. Mendelian randomization (MR) provides a critical method for evaluating the possible causal connections between peripheral circulating blood cells (PCBCs) and UGI cancer. Our study comprehensively employed a two-sample MR analysis. We used publicly available genetic data to survey the causal association between PCBC and UGI cancer. We used inverse variance weighting and weighted median for MR analyses and sensitivity analyses to assess heterogeneity and pleiotropy. In terms of the association between PCBCs and UGI cancer, we found that basophils count (EC: OR = 1.416, 95% CI = 1.125-1.783, = 0.003; GC: OR = 1.623, 95% CI = 1.052-2.505, = 0.029) were all strongly correlated with both EC and GC. Interestingly, Basophil count was a risk factor for both EC and GC. However, no significant correlations were seen between eosinophil, monocyte, lymphocyte or white blood cell count and UGI cancer. The findings of this research corroborate the idea that basophils might serve as a fundamental risk factor for UGI cancer. Further exploration of the underlying mechanisms driving this relationship could provide crucial understanding helpful in creating prospective preventive and treatment methods for UGI cancer.

Background The burden of disease associated with gastrointestinal (GI) tract cancer in Southeast Asia has changed significantly in recent years. This study analyzes data from the Global Burden of Disease Study (GBD)-2021 to examine trends in the burden of GI tract cancers in Southeast Asia from 1990 to 2021, identifies key risk factors, and predicts future trends. Method First, this study obtained data on GI tract cancer by age, sex, etiology, incidence, prevalence, deaths, disability-adjusted life years (DALYs), and risk factor from the GBD-2021 study focused on Southeast Asia data from 1990 to 2021. Secondly, the study also examined the temporal trend of subtype-specific GI tract cancer disease burden in Southeast Asia from 1990 to 2021 using linear regression modeling to calculate estimated annual percentage change (EAPC) values. The autoregressive integrated moving average (ARIMA) model was also used to project the future disease burden from 2022 to 2050. Finally, risk factors for GI tract cancer of different etiologies were also analyzed. Results In 2021, the number of deaths, DALYs, incidence, and prevalence cases of GI tract cancers in Southeast Asia were about 216,074, 5,955,050, 258,629, and 686,835, respectively, with colorectal cancer (CRC) associated with the most severe burden of disease. Between 1990 and 2021, the number of deaths and DALYs associated with CRC and pancreatic cancer (PC) and the corresponding age-standardized rates (ASRs) showed a significant upward trend, with the fastest growth being in PC. The total number of esophageal (EC), gastric (GC), liver (LC), and gallbladder and biliary tract (GBTC) cancer-related deaths and DALYs increased, but the age-standardized rates declined significantly. Predictive data suggest that age-standardized death rate (ASDR), ASR of DALYs, age-standardized incidence rate (ASIR), and age-standardized prevalence rate (ASPR) will continue to decline in EC, GC, and LC, with the most pronounced declines, especially in GC. Overall, ASRs will continue to rise in the cases of CRC, PC, and GBTC cancers. ASDRs associated with GI tract cancers are greatest among those over 90 years of age. The burden of disease is significantly greater in men than in women, and this gender-induced difference is most pronounced in LC. Conclusion While the disease burden of various types of gastrointestinal (GI) cancers in Southeast Asia is experiencing both increases and declines, the overall burden remains significant, with the total number of cases expected to rise in the coming years. To alleviate the impact of severe GI cancers, public health professionals and policymakers must proactively develop and adapt prevention and control strategies, ensuring they are aligned with the shifting disease trends and the evolving risk factors associated with each type of GI tumor.