BMC Medical Genomics最新文献

Background: Apolipoprotein D (APOD), a member of the lipocalin superfamily, plays a pivotal role in apoptosis, cancer, immune responses, and neural injury repair. Its association with various cancer types has been well-documented, but its expression and clinical implications in oral squamous cell carcinoma (OSCC) remain underexplored. Our study aims to investigate the expression and clinical significance of APOD in OSCC.

Methods: A comprehensive analysis of APOD mRNA and protein expression in OSCC was conducted using multi-omics data from TCGA, GEO, and CPTAC databases. The findings were validated through qRT-PCR and immunohistochemistry (IHC) on OSCC tissue samples. Diagnostic and prognostic potential of APOD was assessed using summary receiver operating characteristic (sROC) curves and Kaplan-Meier survival analysis. Multivariate Cox regression analysis was performed to adjust for confounding factors and identify independent prognostic markers for survival. Gene set enrichment analysis (GSEA) was used to explore the signaling pathways associated with APOD and their biological relevance. Ethical approval for research involving human subjects was obtained from an ethics committee.

Results: Analysis of public databases revealed significant downregulation of both APOD mRNA and protein in OSCC tissues compared to normal mucosal controls. Results from clinical samples corroborated these findings. The sROC analysis indicated that APOD may serve as a promising diagnostic biomarker for OSCC. Multivariate Cox regression analysis identified pathological T stage as an independent prognostic factor, independent of clinical T stage and lymphovascular invasion, while APOD, although associated with prognosis, was not a robust predictor. GSEA highlighted a strong positive correlation between APOD expression and key components of Type I interferon signaling (JAK1, TYK2, STAT2), suggesting that APOD downregulation may contribute to OSCC progression by inhibiting the Type I interferon-JAK-STAT pathway.

Conclusion: APOD expression is significantly reduced in OSCC, demonstrating potential as a diagnostic and prognostic biomarker. Its downregulation may facilitate disease progression through disruption of the Type I interferon-mediated JAK-STAT signaling pathway.

Propionic acidemia (PA) is a rare autosomal recessive metabolic disorder caused by functional deficiency of propionyl-CoA carboxylase, clinically characterized by life-threatening ketoacidosis, hyperammonemia, and multiorgan dysfunction. Due to its nonspecific clinical manifestations, PA is frequently misdiagnosed or only identified during severe metabolic crises. This study reports a Chinese family with a history of offspring affected by PA. Through whole-exome sequencing and Sanger validation of fetal amniotic fluid and parental peripheral blood samples, two novel compound heterozygous variants in the PCCB gene were identified in the fetus, initially classified as variants of uncertain significance (VUS) per ACMG guidelines. Subsequent functional studies and amniotic fluid metabolomic analyses were performed. The results demonstrated that the paternal PCCB c.366_372 + 7del variant caused exon 3 skipping(p.Phe102_Gln124del) or exon 2-3 skipping (p.Gly62_Gln124del), while the maternal c.183 + 6T > G variant resulted in intron 1 retention (p.Gly62Valfs*10), both leading to protein truncation and aberrant mRNA splicing. Metabolomic analysis demonstrated significantly elevated C3 levels and an increased C3/C2 ratio, consistent with PA diagnosis. These novel PCCB splicing variants expand the mutational spectrum of PA and demonstrate the clinical utility of integrated genomic-metabolomic analysis for prenatal diagnosis and genetic counseling in high-risk PA families.

Background: Osteoarthritis (OA) is a chronic degenerative joint disease influenced by genetic, environmental, and immunological factors. Vitamin D exerts immunomodulatory and anti-inflammatory effects through the vitamin D receptor (VDR), and genetic variation in the VDR gene may influence susceptibility to OA. However, data from Middle Eastern and Kurdish populations remain limited.

Objective: This study aimed to evaluate the association between serum vitamin D status and four common VDR gene polymorphisms (FokI, ApaI, TaqI, and BsmI) in Kurdish adults with knee osteoarthritis.

Methods: A hospital-based case-control study was conducted, including 100 OA patients and 100 healthy controls recruited in Erbil, Iraq. Serum vitamin D levels were measured biochemically, and VDR polymorphisms were genotyped using PCR-RFLP and sequencing. Association analyses were performed for polymorphic loci using univariate logistic regression.

Results: No allelic or genotypic variation was detected at the FokI (rs2228570), ApaI (rs7975232), or TaqI (rs731236) loci, indicating allele fixation in this population. In contrast, the BsmI (rs1544410) polymorphism exhibited significant variability. The AA genotype was significantly more frequent among OA patients than controls and was associated with increased odds of OA (OR = 2.26, 95% CI = 1.21-4.23; p = 0.006).

Conclusions: The findings indicate that the VDR BsmI polymorphism is associated with knee osteoarthritis in the Kurdish population, whereas FokI, ApaI, and TaqI loci were non-polymorphic. These results highlight population-specific genetic variation within the VDR gene and underscore the need for larger studies incorporating functional validation to clarify the biological relevance of BsmI variation in osteoarthritis.