RNA N6-Methyladenosine Patterns in Hepatocellular Carcinoma Reveal a Distinct Immune Infiltration Landscape and Clinical Significance.

BACKGROUND RNA N6-methyladenosine (m6A) methylation, the most abundant and prominent form of epigenetic modification, is involved in hepatocellular carcinoma (HCC) initiation and progression. However, the role of m6A methylation in HCC tumor microenvironment (TME) formation is unexplored. This study aimed to reveal the TME features of HCC patients with distinct m6A expression patterns and establish a prognostic model based on m6A signatures for HCC cohorts. MATERIAL AND METHODS We classified the m6A methylation patterns in 365 HCC samples based on 21 m6A modulators using a consensus clustering algorithm. Single-sample gene set enrichment analysis algorithm was used to quantify the abundance of immune cell infiltration. Gene set variation analysis revealed the biological characteristics between the m6A modification patterns. The m6A-based prognostic model was constructed using a training set with least absolute shrinkage and selection operator regression and validated in internal and external datasets. RESULTS Two distinct m6A modification patterns exhibiting different TME immune-infiltrating characteristics, heterogeneity, and prognostic variations were identified in the HCC cohort. After depicting the immune landscape of TME in HCC, we found patients with high LRPPRC m6A modulator expression had depletion of T cells, cytotoxic cells, dendritic cells, and cytolytic activity response. A high m6A score, characterized by suppression of immunity, indicated an immune-excluded TME phenotype, with poor survival. A nomogram was developed to facilitate HCC clinical decision making. CONCLUSIONS Our results highlight the nonnegligible role of m6A methylation in TME formation and reveal a potential clinical application of the m6A-associated prognostic model for patients with HCC.

The effects of specific vegetable subtypes on constipation incidence in the general United States population.

Background: While the intake of larger quantities of vegetables has been linked to a reduction in constipation risk, which vegetables in particular underlie this risk reduction remains incompletely understood. As such, the present study was developed to explore correlations between the intake of particular vegetable types and the risk of constipation. Methods: This cross-sectional analysis was based on data from the National Health and Nutrition Examination Survey (NHANES) collected from 2005-2010. Classifications and intake assessments for different vegetables were assessed with the Food Patterns Equivalents Database (FPED), while stool frequency or stool consistency was used to define constipation. Relationships between the intake of particular vegetable components and constipation were assessed through a weighted logistic regression approach. Subgroup and restricted cubic spline (RCS) regression analyses were further employed to explore associations between specific vegetable subtypes and constipation. Results: This study included 13,860 eligible subjects, of whom 1,405 and 12,455 were respectively classified into the constipated and non-constipated groups. Following multivariate adjustment, the intake of non-starchy vegetables including orange, red, dark green, and other vegetables was found to be positively associated with a reduction in constipation risk. In contrast, constipation was unrelated to total starchy vegetable or potato intake. Tomatoes, in particular, were associated with a marked decrease in constipation risk (odds ratios: 0.80, 95% confidence interval: 0.71-0.91). These results were confirmed through RCS and subgroup analyses. Conclusion: Non-starchy vegetables, particularly tomatoes, were found to be associated with a pronounced reduction in constipation risk, which was unaffected by the intake of potatoes or starchy vegetables.

Characterizing the relationships between dietary indices, gallstone prevalence and the need for gallbladder surgery in the general US population.

Background: The dietary inflammatory index (DII) and composite dietary antioxidant index (CDAI) were developed as tools for use when seeking to assess the potential inflammatory and antioxidant activity of a given diet, respectively. The associations between these indices and gallstone incidence remain largely unexplored. Objective: The present study sought to clarify how both the DII and the CDAI are related to gallstone incidence and age at first gallbladder surgery among adults in the USA. Methods: Cross-sectional data from the 2017-2020 cycles of the National Health and Nutrition Examination Survey (NHANES) pertaining to 12,426 individuals were used to conduct the present study. Data from 2 days with 24-h dietary recall were employed when calculating DII and CDAI scores. Relationships between dietary indices and the incidence of gallstones were assessed through logistic regression analyses, while linear regression analyses were employed to characterize how these indices are associated with the age at first gallbladder surgery. Results: Higher DII scores and lower CDAI scores, which, respectively, denote diets with greater inflammatory potential and reduced antioxidant potential, were found to be associated with higher gallstone incidence even following adjustment for potential confounding factors. Smooth curve fitting suggested that the association between DII and gallstones was nearly linear, whereas that between CDAI and gallstone incidence was nonlinear. Higher DII values were also related to first gallbladder surgery at an earlier age (ß = -0.64, 95% CI: -1.26, -0.02). Conclusion: These results emphasize the benefits of anti-inflammatory diets rich in antioxidants, which may help reduce gallstone incidence among adults in the USA. Higher DII scores may also predict the need for gallbladder surgery at a younger age.

The relationship between dietary intake of live microbes and insulin resistance among healthy adults in the US: a cross-sectional study from NHANES 2003-2020.

Dietary intake of live microbes may benefit human health, but less is known about the role in insulin resistance. This study was developed with the goal of evaluating potential relationships between IR and dietary live microbes. The National Health and Nutrition Examination Survey (NHANES) dataset was leveraged to collect data from 6,333 subjects 18 + years of age. The Sanders system for the classification of dietary live microbe intake (containing Low (< 104 CFU/g), Medium (104-107 CFU/g), or High (> 107 CFU/g) levels of live microbes) was then used to separate these patients into three groups (low, medium, or high). Fasting blood glucose and insulin levels were used to approximate IR based on the homeostasis model of insulin resistance (HOMA-IR). Weighted linear regressions were used to assess the relationship between IR and live microbe intake. After fully adjusting for confounding factors, subjects in the groups exhibiting medium and high levels of live microbe intake exhibited HOMA-IR scores that were below those of subjects in the low group. The relationship between live microbe intake and HOMA-IR scores was also potentially impacted by ethnicity. In summary, a negative correlation was detected between dietary live microbe intake and HOMA-IR values.

Gastric Cancer Tumor Microenvironment Characterization Reveals Stromal-Related Gene Signatures Associated With Macrophage Infiltration.

The tumor microenvironment (TME) has attracted attention owing to its essential role in tumor initiation, progression, and metastasis. With the emergence of immunotherapies for various cancers, and their high efficacy, an understanding of the TME in gastric cancer (GC) is critical. The aim of this study was to investigate the effect of various components within the GC TME, and to identify mechanisms that exhibit potential as therapeutic targets. The ESTIMATE algorithm was used to quantify immune and stromal components in GC samples, whose clinicopathological significance and relationship with predicted outcomes were explored. Low tumor mutational burden and high M2 macrophage infiltration, which are considered immune suppressive characteristics and may be responsible for unfavorable prognoses in GC, were observed in the high stromal group (HR = 1.585; 95% CI, 1.112-2.259; P = 0.009). Furthermore, weighted correlation network, differential expression, and univariate Cox analyses were used, along with machine learning methods (LASSO and SVM-RFE), to reveal genome-wide immune phenotypic correlations. Eight stromal-relevant genes cluster (FSTL1, RAB31, FBN1, ANTXR1, LRRC32, CTSK, COL5A2, and ENG) were identified as adverse prognostic factors in GC. Finally, using a combination of TIMER database and single-sample gene set enrichment analyses, we found that the identified genes potentially contribute to macrophage recruitment and polarization of tumor-associated macrophages. These findings provide a different perspective into the immune microenvironment and indicate potential prognostic and therapeutic targets for GC immunotherapies.

IRF1-mediated immune cell infiltration is associated with metastasis in colon adenocarcinoma.

BACKGROUND: Evidence suggests that metastasis is chiefly responsible for the poor prognosis of colon adenocarcinoma (COAD). The tumor microenvironment plays a vital role in regulating this biological process. However, the mechanisms involved remain unclear. The aim of this study was to identify crucial metastasis-related biomarkers in the tumor microenvironment and investigate its association with tumor-infiltrating immune cells. METHODS: We obtained gene expression profiles and clinical information from The Cancer Genome Atlas database. According to the "Estimation of STromal and Immune cells in MAlignant Tumor tissue using Expression data" algorithm, each sample generated the immune and stromal scores. Following correlation analysis, the metastasis-related gene was identified in The Cancer Genome Atlas database and validated in the GSE40967 dataset from Gene Expression Omnibus. The correlation between metastasis-related gene and infiltrating immune cells was assessed using the Tumor IMmune Estimation Resource database. RESULTS: The analysis included 332 patients; the metastatic COAD samples showed a low immune score. Correlation analysis results showed that interferon regulatory factor 1 (IRF1) was associated with tumor stage, lymph node metastasis, and distant metastasis. Furthermore, significant associations between IRF1 and CD8+ T cells, T cell (general), dendritic cells, T-helper 1 cells, and T cell exhaustion were demonstrated by Spearmans correlation coefficients and P values. CONCLUSIONS: The present findings suggest that IRF1 is associated with metastasis and the degree of immune infiltration of CD8+ T cells (general), dendritic cells, T-helper 1 cells, and T cell exhaustion in COAD. These results may provide information for immunotherapy in colon cancer.