PLEKHA4 is Associated with Tumour Microenvironment, Stemness, Proliferation and Poor Prognosis of Gliomas

Background: Glioma is the most common intracranial malignancy. Immune-infiltration and tumour stemness are associated with the prognosis of glioma. Although pleckstrin homology containing family A, number 4 (PLEKHA4) is widely expressed in various human cancers, its role in glioma remains unclear. Methods: We examined the features and clinical significance of PLEKHA4 in gliomas by analysing relevant data from the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases. Gene set enrichment analysis (GSEA) was performed to determine the possible functions and pathways involving PLEKHA4 in glioma. The relationship between PLEKHA4 expression and the degree of oncogenic dedifferentiation was analysed using stemness scores (ss) calculated from epigenetic and transcriptomic features. We also explored the relationship between PLEKHA4 expression and immune cell infiltration in gliomas using the CIBERSORT databases. Furthermore, drug sensitivity analysis was performed using datasets from the GDSC and GTRP databases. In addition, we performed relevant in vitro experimental studies. Results: PLEKHA4 DNA hypomethylation status was associated with its high expression in glioma tissues as well as poor prognoses. Univariate and multivariate Cox analyses indicated that PLEKHA4 expression may be considered as an independent prognostic factor in patients with glioma. GSEA indicated that high PLEKHA4 expression was associated with Janus kinase (JAK)/signal transducer and activator of transcription (STAT), Wingless-Type MMTV Integration Site Family (Wnt), JUN N-terminal kinase (JNK) signalling pathways and involved in apoptotic, cytoskeletal, and cell adhesion biological processes (BPs). In addition, increased PLEKHA4 expression was associated with higher glioma stemness scores than lower PLEKHA4 expression levels. Furthermore, the expression of PLEKHA4 was shown to be associated with glioma infiltration by CD4+ T cells, B cells, neutrophils, macrophages, and dendritic cells. Drug sensitivity analysis also showed that PLEKHA4 expression was negatively correlated with the sensitivity of several small molecule kinase inhibitors. Furthermore, in vitro experiments confirmed that PLEKHA4 knockdown inhibited the proliferation of glioma cells. Conclusions: PLEKHA4 is highly expressed in glioma tissues and correlated with tumour stemness, immune cell infiltration and proliferation, suggesting its potential as a novel prognostic biomarker and therapeutic target in glioma

Relationship between dietary pattern and depressive symptoms: an international multicohort study

Abstract Background Several previous studies have shown that dietary patterns are associated with the incidence of depressive symptoms. However, the results have been inconsistent. This study aimed to prospectively investigate the association between dietary patterns and the risk of depressive symptoms in two large cohort studies. Methods The Tianjin Chronic Low-grade Systemic Inflammation and Health (TCLSIH) cohort study included a total of 7,094 participants living in Tianjin, China from 2013 to 2019, and the UK Biobank cohort study includes 96,810 participants who were recruited from 22 assessment centers across the UK taken between 2006 and 2010. All participants were free of a history of cardiovascular disease (CVD), cancer, and depressive symptoms at baseline. Dietary patterns at baseline were identified with factor analysis based on responses to a validated food frequency questionnaire in TCLSIH or Oxford WebQ in UK Biobank. Depressive symptoms were evaluated using the Chinese version of the Zung Self-Rating Depression Scale (SDS) in TCLSIH or hospital inpatient records in UK Biobank. Cox proportional hazards regression models were used to estimate the association between dietary patterns and depressive symptoms. Results A total of 989, and 1,303 participants developed depressive symptoms during 17,410 and 709,931 person-years of follow-up. After adjusting for several potential confounders, the multivariable HRs (95% CIs) of the depressive symptoms were 0.71 (0.57, 0.88) for traditional Chinese dietary pattern, 1.29 (1.07, 1.55) for processed animal offal included animal food dietary pattern, and 1.22 (1.02, 1.46) for sugar rich dietary pattern in TCLSIH (all Q4 vs Q1). In the UK Biobank, the HRs (95% CIs) of depressive symptoms were 1.39 (1.16, 1.68) for processed food dietary pattern (Q4 vs Q1), 0.90 (0.77, 1.00) for healthy dietary pattern (Q3 vs Q1), and 0.89 (0.75, 1.05) for meat dietary pattern (Q4 vs Q1) in the final adjusted model. Conclusion Dietary patterns rich in processed foods were associated with a higher risk of depressive symptoms, and following a traditional Chinese dietary pattern or healthy dietary pattern was associated with a lower risk of depressive symptoms, whereas meat dietary pattern was not associated

CBD2: A functional biomarker database for colorectal cancer

Abstract The rapidly evolving landscape of biomarkers for colorectal cancer (CRC) necessitates an integrative, updated repository. In response, we constructed the Colorectal Cancer Biomarker Database (CBD), which collected and displayed the curated biomedicine information for 870 CRC biomarkers in the previous study. Building on CBD, we have now developed CBD2, which includes information on 1569 newly reported biomarkers derived from different biological sources (DNA, RNA, protein, and others) and clinical applications (diagnosis, treatment, and prognosis). CBD2 also incorporates information on nonbiomarkers that have been identified as unsuitable for use as biomarkers in CRC. A key new feature of CBD2 is its network analysis function, by which users can investigate the visible and topological network between biomarkers and identify their relevant pathways. CBD2 also allows users to query a series of chemicals, drug combinations, or multiple targets, to enable multidrug, multitarget, multipathway analyses, toward facilitating the design of polypharmacological treatments for CRC. CBD2 is freely available at http://www.eyeseeworld.com/cbd