Ulcerative colitis is a common inflammatory bowel disease with a complex genetic and immune etiology. Immune infiltration plays a vital role in the development of ulcerative colitis. To explore potential biomarkers for ulcerative colitis and analyze characteristics of immune cell infiltration, we used bioinformatic analyses, including machine learning algorithms, cell type deconvolution methods, and pathway enrichment methods. In this study, we identified 216 differentially expressed mRNAs (DEMs), of which 153 were upregulated, and 63 were downregulated genes. DEMs were mainly enriched in infiltrating neutrophils and regulation of leukocyte migration. Moreover, eight candidate biomarkers, DPP10, MST1L, DPP10‐AS1, CEP55, ACSL1, MGP, OLFM4, and SGK1, were identified. Of these candidate biomarkers, MST1L, OLFM4, and DPP10 were then validated in theGSE48958dataset and were predicted to be strongly correlated with infiltrating immune cells of ulcerative colitis. The underlying mechanism of these key genes in the development of colitis was also predicted by gene set variation analysis. To further validate these biomarkers' expression in ulcerative colitis, we determined mRNA levels ofSGK1,CEP55,ACSL1,OLFM4, andDPP10in lipopolysaccharides (LPS)‐stimulated Raw264.7 cells by quantitative reverse transcription‐polymerase chain reaction. We also examinedSGK1,CEP55,ACSL1,OLFM4,DPP10, andMGPexpression in the colon tissues of dextran sodium sulfate‐induced colitis mice. Consistent with the predicted computational results, the mRNA levels of these candidate genes were markedly changed in LPS‐stimulated Raw264.7 cells and inflamed colon tissues. Hence, our findings indicated that these critical genes may act as diagnostic biomarkers for ulcerative colitis and that differential immune infiltration cells may help illustrate the progression of ulcerative colitis.

Recent studies have underscored a potential link between gut microbiota and urological tumors, yet the causal relationship with bladder cancer (BCa) and the role of metabolic pathways remain unclear. Instrumental variables (IVs) for gut microbiota were obtained from genome-wide association studies (GWAS) conducted by the MiBioGen consortium (n = 18,340). GWAS data for BCa were sourced from a comprehensive genome-wide meta-analysis encompassing 23 cohorts. Mendelian randomization (MR) was employed to investigate the causal relationship between gut microbiota and BCa, utilizing inverse variance weighted (IVW) as the primary MR method. Additionally, metabolic pathways associated with these microbiota were analyzed to understand their functional roles in BCa pathogenesis. Sensitivity analyses were conducted to validate all MR results. The MR analysis identified five gut microbiota taxa with a causal association with BCa, with the genus Bilophila notably promoting BCa. Metabolic pathway analysis revealed significant associations between specific pathways and BCa, suggesting that changes in amino acid and NAD metabolism might influence BCa development. Sensitivity analyses indicated no significant heterogeneity or horizontal pleiotropy among the IVs. This study revealed the significant causal relationship between gut microbiota and BCa, particularly identifying Bilophila as a key pathogenic initiator. These findings elucidated the potential impact of metabolic pathways, especially amino acid and NAD metabolism, on the pathogenesis of BCa. They not only laid the foundation for innovative therapeutic strategies but also highlighted the immense potential of microbiota-based interventions in the prevention and treatment of BCa, paving the way for new directions in precision medicine.

Background: Mammalian LEM-domain proteins (LEMs) are encoded by seven genes, including LAP2, EMD, LEMD1, LEMD2, LEMD3, ANKLE1, and ANKLE2. Though some LEMs were involved in various tumor progression, the expression and prognostic values of LEMs in prostate adenocarcinoma (PRAD) have yet to be analyzed. Methods: Herein, we investigated the expression, survival data, and immune infiltration levels of LEMs in PRAD patients from ATCG, TIMER, LinkedOmics, and TISIDB databases. We also further validated the mRNA and protein expression levels of ANKLE1, EMD, and LEMD2 in human prostate tumor specimens by qPCR, WB, and IHC. Results: We found that all LEM expressions, except for that of LAP2, were markedly altered in PRAD compared to the normal samples. Among all LEMs, only the expressions of ANKLE1, EMD, and LEMD2 were correlated with advanced tumor stage and survival prognosis in PRAD. Consistent with the predicted computational results, the mRNA and protein expression levels of these genes were markedly increased in the PRAD group. We then found that ANKLE1, EMD, and LEMD2 expressions were markedly correlated with immune cell infiltration levels. High ANKLE1, EMD, and LEMD2 expressions predicted a worse prognosis in PRAD based on immune cells. DNA methylation or/and copy number variations may contribute to the abnormal upregulation of ANKLE1, EMD, and LEMD2 in PRAD. Conclusions: Taken together, this study implied that ANKLE1, EMD, and LEMD2 were promising prognosis predictors and potential immunotherapy targets for PRAD patients.

Cancer is characterized by chromosomal instability (CIN), which leads to tumor heterogeneity and other malignant features. CIN is caused by abnormal centromere and kinetochore function, which results in aneuploidy, rearrangements, and micronucleus production. Centromere and kinetochore gene misexpression plays a vital role in tumor progression. Here we show that Centromere Protein T (CENPT) is highly expressed in renal carcinoma (RCC) and promotes the tumor proliferation and metastasis of RCC. CENPT is found to be critical for regulating the glutathione (GSH) metabolism pathway because it interacts with γ-glutamyl-cysteine ligase catalytic subunit (GCLC), consequently reducing reactive oxygen species levels and inhibiting ferroptosis. Mechanistically, CENPT increases the catalytic activity of GCLC by directly binding to GCLC ∆213-424aa competitively with glutamate-cysteine ligase modifier subunit (GCLM), consequently induces the GSH synthesis. In turn, GSH increases CENPT expression via transcriptional regulation mediated by the transcription factor ATF2, forming a CENPT-GCLC-GSH feedback loop that enhances the pro-carcinogenic effect of this axis in RCC. Our study identifies CENPT a potential target for RCC via forming a CENPT-GCLC-GSH feedback loop to inhibit ferroptosis. This may support a promising treatment strategy for RCC.