Comprehensive analysis of P2Y family genes expression, immune characteristics, and prognosis in pan-cancer.

BACKGROUND: P2Y receptors are a family of G protein-coupled receptor genes that have an important function in cancer development and metastasis. However, systematic studies have not been conducted on human tumors. This study attempted to explore the role of P2Y family genes (P2Ys) in pan-cancer. METHODS: Gene expression and clinical data were downloaded from The Cancer Genome Alas dataset. Gene differential expression, mutation, prognosis, tumor microenvironment (TME) (containing immune cells infiltration, Estimate/immune/stromal scores, immune checkpoints, immune and molecular subtypes, DNA repair genes and methyltransferase), clinical correlation, protein-protein interaction network and functional enrichment analysis were performed. In addition, experiments such as western blots were performed for validation. RESULTS: Eight P2Ys were differentially expressed in most tumor and normal tissues, and their abnormal expression in a variety of cancers could significantly reduce the survival rate of patients. Expression levels of P2Ys, especially P2Y6, P2Y12, P2Y13, P2Y14, were correlated significantly with immune cells, immune checkpoint genes, immune and molecular subtypes and Estimate/immune/stromal scores in a variety of cancers such as uveal melanoma, liver hepatocellular carcinoma, stomach adenocarcinoma, colorectal cancer (CRC), prostate adenocarcinoma, breast invasive carcinoma and uterine corpus endometrial carcinoma (all p < 0.05). P2Ys play an important role in TME and are involved in immune regulation. In addition, enrichment analysis and western blots showed that the levels of P2Y2 and P2Y6 expression regulate the Akt/GSK-3ß/ß-catenin pathway in CRC, thereby affecting epithelial-to-mesenchymal transition. CONCLUSION: P2Ys may be used as potential pan-cancer biomarkers in prognosis and immunology. They may also be new targets for tumor immunotherapy, which has wide clinical implications.

Gender Differences in Psychological Symptoms and Quality of Life in Patients with Inflammatory Bowel Disease in China: A Multicenter Study.

OBJECTIVE: To explore the gender differences in the psychological symptoms, sleep quality, and quality of life of patients with inflammatory bowel disease (IBD). METHODS: A unified questionnaire was developed to collect clinical data on the psychology and quality of life of IBD patients from 42 hospitals in 22 provinces in China from September 2021 to May 2022. The general clinical characteristics, psychological symptoms, sleep quality, and quality of life of IBD patients of different genders were analyzed via a descriptive statistical analysis. A multivariate logistic regression analysis was conducted, and independent influencing factors were screened to construct a nomogram to predict the quality of life. The consistency index (C-index), receiver operating characteristic (ROC) curve, area under the ROC curve (AUC), and calibration curve were used to evaluate the discrimination and accuracy of the nomogram model. Decision curve analysis (DCA) was used to evaluate the clinical utility. RESULTS: A total of 2478 IBD patients (1371 patients with ulcerative colitis (UC) and 1107 patients with Crohn's disease (CD)) were investigated, including 1547 males (62.4%) and 931 females (37.6%). The proportion of anxiety in females was significantly higher than in males (IBD: 30.5% vs. 22.4%, p < 0.001; UC: 32.4% vs. 25.1%, p = 0.003; CD: 26.8% vs. 19.9%, p = 0.013), and there were differences in the severity of anxiety between the genders (IBD: p < 0.001; UC: p < 0.001; CD: p = 0.050). The proportion of depression in females was higher than in males (IBD: 33.1% vs. 27.7%, p = 0.005; UC: 34.4% vs. 28.9%, p = 0.031; CD: 30.6% vs. 26.6%, p = 0.184), and there were differences in the severity of depression between the genders (IBD: p = 0.004; UC: p = 0.022; CD: p = 0.312). The proportion suffering from sleep disturbances among females was slightly higher than among males (IBD: 63.2% vs. 58.4%, p = 0.018; UC: 63.4% vs. 58.1%, p = 0.047; CD: 62.7% vs. 58.6%, p = 0.210), and the proportion of females with a poor quality of life was higher than that of males (IBD: 41.8% vs. 35.2%, p = 0.001; UC: 45.1% vs. 39.8%, p = 0.049; CD: 35.4% vs. 30.8%, p = 0.141). The AUC values of the female and male nomogram prediction models for predicting poor quality of life were 0.770 (95% CI: 0.7391-0.7998) and 0.771 (95% CI: 0.7466-0.7952), respectively. The calibration diagrams of the two models showed that the calibration curves fitted well with the ideal curve, and the DCA that showed nomogram models could bring clinical benefits. CONCLUSIONS: There were significant gender differences in the psychological symptoms, sleep quality, and quality of life of IBD patients, suggesting that females need more psychological support. In addition, a nomogram model with high accuracy and performance was constructed to predict the quality of life of IBD patients of different genders, which is helpful for the timely clinical formulation of personalized intervention plans that can improve the prognosis of patients and save medical costs.

Comprehensive analysis of immunogenic cell death associated genes expression, tumor microenvironment, and prognosis in hepatocellular carcinoma.

Background: Immunogenic cell death (ICD) plays an important role in the development of cancers. This study attempted to explore the role of ICD in the prognosis of hepatocellular carcinoma (HCC). Methods: Gene expression and clinical data were downloaded from The Cancer Genome Alas and Gene Expression Omnibus dataset. The immune/stromal/Estimate scores of the tumor microenvironment (TME) were calculated by ESTIMATE and CIBERSORT algorithms. Kaplan-Meier analysis, functional enrichment analysis, least absolute shrinkage and selection operator (LASSO) analysis, and univariate and multivariate Cox regression analysis were used for prognostic gene screening and prognostic model construction. The correlation of immune cell infiltration and risk scores was analyzed as well. Molecular docking was used to explore the relevance of related genes to anti-cancer drugs. Results: Ten ICD associated differentially expressed genes in HCC were found, and all of them had good predictive ability for HCC. ICD gene high amount of expression group was associated with poor prognosis (p = 0.015). The TME, immune cell infiltration and gene expression were different between ICD high and low groups (all p < 0.05). Six ICD associated genes (BAX, CASP8, IFNB1, LY96, NT5E and PIK3CA) which could predict the survival status were identified and used to construct the prognostic model for HCC. A risk score was calculated and it could be used as an independent prognostic factor in HCC patients (p < 0.001). In addition, the risk score had a positive correlation with macrophage M0 (r = 0.33, p = 0.0086). Molecular docking indicated that sorafenib could bind strongly to the target protein, representing that sorafenib may exert anticancer effects through these six ICD associated genes. Conclusion: This study established a prognostic model including six ICD associated genes for HCC, which may deepen our understanding of ICD and guide therapy for HCC patients.

Clinical Features of Crohn's Disease Stratified by Age at Diagnosis According to Montreal Classification.

Aim: The differences of clinical characteristics stratified by age at diagnosis especially according to Montreal classification were rarely studied in China. This study aimed to evaluate and compare the clinical features in various groups of CD patients stratified by age at diagnosis. Methods: A cross-sectional study of CD patients was conducted through a stratified sampling according to Montreal classification. Patients were divided into three groups by age at diagnosis: group A1 (<17 years old), group A2 (17 to 40 years old), and group A3 (>40 years old). The clinical characteristics, laboratory tests, radiographic, and endoscopic features were analyzed by statistics. Results: We enrolled 259 CD patients for the study. There was male predominance under 40 years old. Compared to group A1, more female patients were presented in group A3. There were more patients had perianal fistulas in group A1 compared to group A2 and group A3. Compared with group A1, patients in group A2 were associated with lower total protein (TP) levels. The mean TP and platelet count (PC) levels in group A3 were lower than group A1. Patients in group A1 had a lower rate of stricturing (B2) disease behavior than group A2 and group A3, and patients in group A3 who had a B2 disease behavior were higher than group A2. Those differences could guide early treatment or inventions for CD patients who might progress to a more complex disease behavior. Conclusion: CD patients stratified by age at diagnosis according to Montreal classification had different clinical symptoms, laboratory test results as well as disease locations and behaviors.

The Clinical Relevance and Immune Correlation of SLC10 Family Genes in Liver Cancer.

Background and Aim: This study was aimed to reveal the clinical relevance and immune correlation of the SLC10 family genes in liver cancer. Methods: A comprehensive bioinformatics analysis was utilized to determine the gene expression, genetic alterations, DNA methylation, clinical significance, survival association and immune correlation of seven SLC10 family genes in liver cancer. The multiplexed immunohistochemical technique was applied to determine the association between SLC10A3 protein expression and immune cells, and the correlation between SLC10A3 protein and immune checkpoints (PD1 and PD-L1) in a cohort of 32 individuals with liver cancer. Results: The expression of SLC10 family genes was different between normal liver tissues and malignant liver tissues. SLC10A5 showed the highest alteration rate (8%), followed by SLC10A3 (2.8%). Low expression of SLC10A1 was indicative of poor tumor grade and advanced tumor stage in liver cancer. Scatter plots uncovered that expression of SLC10A3 was inversely associated with SLC10A1 and SLC10A5 expression in liver cancer. The expression of SLC10A1 and SLC10A5 was strongly associated with their DNA methylation. SLC10A1 expression was a reliable genetic biomarker for the prediction of survival outcomes in liver cancer population. Expression of SLC10 family genes was remarkably linked with the abundance of most immune infiltrating cells in liver cancer, and SLC10A3 was the most significant member. The multiplexed immunohistochemical technique confirmed that there existed the significant correlations between SLC10A3 protein expression and CD4 T cells, CD20 B cells and the close association with PD-1 in the stromal area from malignant tissues. Conclusion: The expressions of SLC10 family genes were different between normal liver tissues and malignant liver tissues, and they were correlated with each other in liver cancer. SLC10A1 possesses the most significant correlation with survival outcomes. SLC10A3 exhibited the most significant relationship with immune cells, as revealed by bioinformatics analysis and multispectral imaging technique.