Decreased expression of JAK1 associated with immune infiltration and poor prognosis in lung adenocarcinoma.

Janus kinase 1 (JAK1) is a member of the JAK family, which plays an essential and non-redundant role in tumorigenesis. However, the potential role of JAK1 in immune infiltration and prognosis of lung adenocarcinoma (LUAD) remains unclear. The mRNA expression and methylation level of JAK1 in LUAD were examined using the Oncomine and The Cancer Genome Atlas (TCGA) databases, respectively. The correlations between JAK1 expression and its methylation level and clinicopathological parameters were analyzed. The Kaplan-Meier plotter database was used to evaluate the prognostic value of JAK1 in LUAD. The signaling pathways associated with JAK1 expression were identified by performing a GSEA. The CIBERSORT and TIMER databases were used to analyze the correlations between JAK1 and tumor-infiltrating immune cells. In addition, the JAK1 expression and proportion of immune cells in LUAD cell lines were analyzed. The JAK1 expression was remarkably decreased in patients with LUAD and significantly correlated with the clinical features of patients with LUAD. The JAK1 methylation level was increased and negatively correlated with its mRNA expression. A decrease in JAK1 expression was correlated with poor prognosis. The results of GSEA showed that cell adhesion, tumorigenesis, and immune-related signaling pathways were mainly enriched. JAK1 was positively associated with tumor-infiltrating immune cells, and the results of CIBERSORT analysis suggested that JAK1 was correlated with monotypes and M1 macrophages. The results of the TIMER database analysis confirmed that JAK1 was closely associated with the gene markers of M1 macrophages. Thus, JAK1 may serve as a potential prognostic biomarker in LUAD and is associated with immune infiltration.

A meta-analysis of the association between CTLA-4 genetic polymorphism and susceptibility of asthma.

BACKGROUND: Numerous studies have reported an association between cytotoxic T-lymphocyte associated antigen 4 gene (CTLA4) polymorphism and susceptibility to asthma, in different populations, but the results have been inconsistent. We performed a meta-analysis of 19 published case-control studies to obtain a reasonably accurate estimation of the relationship between CTLA4 polymorphism and asthma. METHODS: We searched the Pubmed, EMBASE, Chinese National Knowledge Infrastructure, and Wanfang databases and extracted data from 19 independent, eligible studies. Odds ratios (ORs) with 95% confidence intervals (CIs) and Egger test were separately used to assess the strength of associations and publication bias. RESULTS: A total of 19 case-control studies involving 4831 cases and 4534 controls were identified. The combined results revealed that there was significant association between the +49A/G polymorphism and asthma (for GG + GA vs. AA: OR = 0.82, 95% CI = 0.70-0.97, P = .02). Stratification by race or age indicated a significant association between the CTLA-4 +49 GA+GG genotype and asthma in Asians (OR = 0.80, 95% CI = 0.68-0.95, P = .01) and children (OR = 0.75, 95% CI = 0.62-0.90, P = .002), but there was no association in whites (OR = 0.94, 95% CI = 0.80-1.10, P = .44) and adults (OR = 0.85, 95% CI = 0.68-1.06, P = .15). Additionally, there was a significant association with atopic asthma under the random-effects model (OR = 0.81, 95% CI = 0.67-0.98, P = .03). In addition, there was no significant association between the -318 C/T polymorphism and asthma risk. CONCLUSIONS: Our meta-analysis results suggested that the +49A/G polymorphism in CTLA-4 was an important risk factor for asthma susceptibility, especially in Asian individuals, children, and atopic patients.