Methyltransferase-like 3 (METTL3) belongs to the class I MTase family, and it has been proved that METTL3 is highly expressed in a variety of tumors and promotes tumor progression. Our previous studies have shown that METTL3 is highly expressed in gastric cancer tissues compared with para-cancer tissues, and its expression level is negatively correlated with good postoperative prognosis of patients. To explore the expression of METTL3 in colorectal cancer (CRC) tissue and the relationship between METTL3 and the clinicopathologic features and prognosis of CRC patients. The expression of METTL3 in cancer tissues and adjacent tissues of 180 patients with colorectal cancer was analyzed by tissue microarray and immunohistochemistry. The clinicopathologic features of patients with different METTL3 expression levels were analyzed. The expression level of METTL3 in colorectal cancer tissues was higher than that in adjacent tissues (P < .05). There were statistically significant differences in the expression of METTL3 in clinical stage, survival time and distant metastasis (all P < .05). The expression level of METTL3 in colorectal cancer tissues with tumor-node-metastasis stage III and IV and distant metastasis was higher than that in clinical stage I and II and without distant metastasis (P < .05). Patients with high METTL3 expression had a higher overall mortality rate compared to patients with low METTL3 expression, and the difference was statistically significant (P < .05). Univariate Cox regression analysis suggested that tumor distant metastasis, vascular invasion, pathological grade, lymph node metastasis and METTL3 expression level were risk factors for overall survival in CRC patients (all P < .05). Multivariate Cox regression analysis suggested that low pathological grade (hazard ratio = 1.695, 95% confidence interval: 1.116–2.274, P = .005) and high METTL3 expression (hazard ratio = 2.156, 95% confidence interval: 1.587–2.725, P < .001) could be used as independent risk factors for prognosis assessment. The expression of METTL3 was increased in colorectal cancer, and METTL3 was closely related to clinical stage, distant metastasis and prognosis of colorectal cancer.

Primary sclerosing cholangitis (PSC), a chronic cholestatic liver condition, is frequently associated with inflammatory bowel disease. Specific immune cells have been implicated in PSC pathogenesis with the emergence of the “microbiota” and “gut lymphocyte homing” hypotheses, albeit their identities remain controversial. The first genome-wide association analysis leveraged nonoverlapping data from 3757 Europeans to evaluate 731 immunophenotypes. A genome-wide association analysis comprising 2871 cases and 12,019 controls yielded summary statistics for PSC. An inverse-variance weighted (IVW) analysis was performed to identify immunophenotypes causally related to PSC, and the results were validated using weighted mode, MR-Egger, and weighted median methods. Comprehensive sensitivity analyses were performed to verify the robustness, heterogeneity, and horizontal pleiotropy of the results. IVW analysis revealed 26 immune traits exhibiting causal associations with PSC. CD3 on HLA-DR+ CD4+ (IVW odds ratio [OR]: 0.904; 95% confidence interval [CI]: 0.828–0.986, P =  .023) and CD3 on secreting Treg (IVW OR: 0.893; 95% CI: 0.823–0.969, P =  .007) were negatively associated with PSC susceptibility and demonstrated high consistency across the 3 validation methods. Moreover, 7 other immune traits, including CD39+ resting Treg absolute cell (IVW OR = 1.083, 95% CI: 1.013–1.157, P =  .019), CD39+ secreting Treg absolute cell (IVW OR = 1.063, 95% CI: 1.012–1.118, P =  .015), CD3 on naive CD8br (IVW OR = 0.907, 95% CI: 0.835–0.986, P =  .022), CD3 on CD39+ activated Treg (IVW OR = 0.927, 95% CI: 0.864–0.994, P =  .034), CD28 on resting Treg (IVW OR = 0.724, 95% CI: 0.630–0.833, P =  5.95E-06), and CD39 on CD39+ CD4+ (IVW OR = 1.055, 95% CI: 1.001–1.112, P =  .044) exhibited consistent results in the Weighted Median and Weighted Mode validation methods. Moreover, no significant heterogeneity or horizontal pleiotropy was observed across the single nucleotide polymorphisms. The leave-one-out results revealed that sequentially eliminating each single nucleotide polymorphism had no significant influence on model effect estimates or qualitative inference. This study evaluated potential causal links between 731 immune traits and PSC susceptibility. Twenty-six immune traits were identified using the IVW method. Verification across multiple methods revealed 9 immune traits with a plausible causal connection to PSC. These findings may uncover mechanistic pathways and novel therapeutic approaches.