The prognostic and immunological role of FKBP1A in an integrated muti-omics cancers analysis, especially lung cancer.

BACKGROUND AND AIM: FKBP1A, a gene encoding the FK506-binding protein 1A, has emerged as a significant player in cancer progression and prognosis. This study aimed to comprehensively investigate the multifaceted role of FKBP1A in cancer, focusing on its differential expression patterns, prognostic implications, genetic alterations, and associations with the tumor microenvironment. METHODS AND RESULTS: Using large-scale datasets, including GTEx, TCGA, HPA, and cBioPortal, we analyzed FKBP1A expression across normal tissues and various cancer types. Our findings revealed that FKBP1A exhibited aberrant upregulation in most human cancers, making it a potential biomarker for malignancy. Moreover, FKBP1A expression correlated with poor overall survival, disease-specific survival, disease-free interval, and progression-free interval in several cancers, indicating its prognostic significance. Genetic alteration analysis showed that FKBP1A gene amplification was prevalent, particularly in ovarian cancer. Furthermore, FKBP1A expression was associated with tumor mutational burden and microsatellite instability, highlighting its potential involvement in tumor-immune response. Notably, FKBP1A expression positively correlated with stromal and immune cell scores, suggesting its role in shaping the tumor microenvironment. Additionally, according to the functional enrichment analysis, experimental validation in lung adenocarcinoma confirmed the role of FKBP1A through the regulation of EGFR signaling by apoptosis, which is consistent with drug sensitivity analysis to some extent. CONCLUSION: In conclusion, FKBP1A exhibits differential expression in cancer, serves as a prognostic indicator, undergoes genetic alterations, and influences the tumor-immune microenvironment. These findings shed light on the multifaceted role of FKBP1A in cancer development and progression, suggesting its potential as a therapeutic target and guidance of clinical drugs selection, and provide valuable insights into patient prognosis for interventions based on pharmaceuticals.

Body composition and risk of liver cancer: a population-based prospective cohort study on gender difference.

Background: Obesity is a common and highly convincing risk factor for many cancers, including liver cancer. Sex disparities in the body composition and regulatory mechanisms involved in energy homeostasis may contribute to the difference in the incidence of cancer. However, evidence on the gender-specific association between body composition and liver cancer incidence is limited. We performed this study to investigate the linear and non-linear associations of body composition with liver cancer risk by gender. Materials and methods: This prospective analysis included 4,75,659 participants free of cancer, based on the UK Biobank. We used Cox proportional hazard models to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) after adjusting for potential confounders. Restricted cubic spline was performed to investigate the potential non-linear associations. Results: During a median follow-up, 275 cases (174 male patients and 101 female patients) of liver cancer were identified. Male patients in the highest body fat percentage group are more likely to develop liver cancer (HR = 1.89, 95% CI: 1.17-3.03) compared with those in the lowest group. The one-unit increase of whole-body fat mass, arm fat mass, and trunk fat mass was associated with 1.03-, 1.14-, and 1.05-fold increased risk of liver cancer in male subjects, respectively. U-shaped associations of body composition with liver cancer risk were observed in the female subjects. Both high and low levels of whole-body fat-free mass, particularly in the arm and trunk, were associated with an increased risk of liver cancer. Conclusion: This study found a gender-specific association between body composition and liver cancer risk and provided evidence for individualized weight management for the prevention of liver cancer.

Mesenchymal stem cells attenuate sepsis-induced liver injury via inhibiting M1 polarization of Kupffer cells.

Sepsis is a leading cause of death in intensive care units that can result in acute hepatic damage. Animal experiments and clinical trials have shown that mesenchymal stem cell (MSC) therapy has some beneficial in several liver diseases. However, the protective effects of MSC therapy on sepsis-induced hepatic damage and associated mechanisms are not completely understood. The aim of the present study was to investigate the effects of MSCs on sepsis-induced liver injury and underlying mechanisms. A rat model of sepsis-induced liver injury was established by cecal ligation and puncture, and serum alanine aminotransferase and aspartate transaminase activities as well as liver histological changes were measured. Inflammatory cytokines, Kupffer cell M1 phenotype markers, and associated signal molecules were also determined in septic rats and in lipopolysaccharide (LPS)-treated Kupffer cells. Our results showed that injection of MSCs attenuated sepsis-induced liver injury. Treatment with MSCs inhibited activation of Kupffer cells towards M1 phenotype, attenuated TNF-α and IL-6 expression, and promoted IL-4 and IL-10 expression in septic rats and LPS-treated Kupffer cells. Furthermore, MSCs also inhibited the nuclear translocation of nuclear factor-kappa B in LPS-challenged Kupffer cells and the liver of septic rats. These results indicated that MSCs attenuated sepsis-induced liver injury through suppressing M1 polarization of Kupffer cells.

Fetal But Not Maternal Angiotensin Converting Enzyme (ACE)-2 Gene Rs2074192 Polymorphism is Associated with Increased Risk of Being a Small For Gestational Age (SGA) Newborn.

BACKGROUND/AIMS: The maternal and fetal Renin-Angiotensin-System is involved in the control of pregnancy outcomes such as blood pressure control and gestational age. However, very little is known about the impact of the angiotensin converting enzyme 2 (ACE2) on pregnancy outcome. We thus performed a prospective clinical observational study analyzing the association of maternal and fetal ACE2 gene rs2074192 polymorphism with fetal growth during pregnancy. METHODS: 898 singleton pregnant women were prospectively recruited. 739 pregnant women finally participated in the study and were genotyped. 474 women also donated umbilical cord blood for gene analysis of their offspring. All data such as basic demographic information, data from birth records, biochemical and immunological parameters, as well as Doppler ultrasonographic findings during pregnancy were collected. Fetal and maternal ACE2 gene rs2074192 polymorphism was genotyped by DNA sequencing. RESULTS: Our analysis showed that the maternal ACE2 gene rs2074192 polymorphism was not associated with gestational hypertension, gestational diabetes mellitus, anemia, postpartum hemorrhage and fetal growth. However, neonates having rs2074192 T allele were more likely to be born as small for gestational age (SGA) babies. After multivariable logistic regression considering known confounding, we could demonstrate that the neonatal rs2074192 T allele was an independent risk factor for SGA (OR: 22.93, 95%CI: 1.26∼418.77, P< 0.05). CONCLUSION: This is the first study showing that the babies but not their mothers with ACE2 gene rs2074192 T allele had a high risk for SGA, which contributes to metabolic syndrome and cardiovascular diseases in later life.

[Combined therapy with daclatasvir plus asunaprevir for chronic hepatitis C genotype 1b: a case report].

OBJECTIVE: The combination therapy with daclatasvir and asunaprevir can achieve a high sustained viral response rate against hepatitis C virus (HCV) genotype 1, but so far this regimen has not been reported in the treatment of Chinese patients with chronic hepatitis C (CHC) genotype 1b. Here we report a case of CHC genotype 1b in a 44-year-old female chinese patient who was treated with this regimen for 24 weeks. The patient showed sustained viral response after the treatment and was clinically cured. During the treatment, the patient experienced a transient elevation of serum total bilirubin accompanied by lowered hemoglobin fluctuating between 100 and 110 g/L.