RESUMEN
BACKGROUND: The chemosensitivity of osteosarcoma patients to MTX is closely related to prognosis. There is currently a lack of advance prediction methods for MTX sensitivity. OBJECTIVE: We proposed novel peri-osteosarcoma fat parameters based on computed tomography (CT) to evaluate the chemotherapy response preoperatively and calculate the correlation between image characteristics and methotrexate (MTX) blood concentration and systemic inflammation. MATERIALS AND METHODS: Pediatric patients with osteosarcoma (OS) who were treated with high-dose MTX were retrospectively studied and grouped according to postoperative Huvos classification. Clinical data were collected and reviewed. Image characteristics including peri-osteosarcoma fat volume and fat attenuation index were measured using the threshold method based on CT images. Statistical significance, correlation and prediction performance were performed. RESULTS: Eighteen patients (good response (GR) group/poor response (PR) group: 10/8) was enrolled. MTX peak value at 6 h differed significantly between the two groups which was significantly higher in GR group (745.1 µmol/L vs 529.0 µmol/L p = 0.001). Peri-osteosarcoma fat attenuation index was significantly lower in GR group compared with that in PR group (- 104.90 vs. - 97.19, p < 0.0001). MTX blood concentration at 6 h negatively correlated with peri-osteosarcoma fat attenuation index (R = - 0.519, p = 0.027). In addition, 6 h MTX blood concentration (OR 0.974; 95% CI 0.951-0.998, p = 0.037) and FAI (OR 2.108; 95% CI 1.047-4.243, p = 0.037) were, respectively, independently related to good response to chemotherapy. The prediction performance on chemotherapy response of peri-osteosarcoma fat attenuation index and 6 h MTX blood concentration were both good with the comparable area under the ROC curve (0.950, 95% CI 0.856-1.000 and 0.963, 95% CI 0.878-1.00). CONCLUSIONS: Peri-osteosarcoma fat parameters based on CT were associated with the chemotherapy response and the MTX blood concentration, but not with the systemic inflammation. Combined with the requirement of current clinical practice, peri-osteosarcoma fat parameters may have the potential to be valuable image characteristics for monitoring chemotherapy response in OS pediatric patients.
Asunto(s)
Neoplasias Óseas , Osteosarcoma , Humanos , Niño , Estudios Retrospectivos , Osteosarcoma/diagnóstico por imagen , Osteosarcoma/tratamiento farmacológico , Metotrexato/uso terapéutico , Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/tratamiento farmacológico , Inflamación , TomografíaRESUMEN
Excess O-glycosylation of proteins by O-linked beta-N-acetylglucosamine (O-GlcNAc) may be involved in the pathogenesis of type 2 diabetes. The enzyme O-GlcNAc-selective N-acetyl-beta-d glucosaminidase (O-GlcNAcase) encoded by MGEA5 on 10q24.1-q24.3 reverses this modification by catalyzing the removal of O-GlcNAc. We have previously reported the linkage of type 2 diabetes and age at diabetes onset to an overlapping region on chromosome 10q in the San Antonio Family Diabetes Study (SAFADS). In this study, we investigated menangioma-expressed antigen-5 (MGEA5) as a positional candidate gene. Twenty-four single nucleotide polymorphisms (SNPs), identified by sequencing 44 SAFADS subjects, were genotyped in 436 individuals from 27 families whose data were used in the original linkage report. Association tests indicated significant association of a novel SNP with the traits diabetes (P = 0.0128, relative risk = 2.77) and age at diabetes onset (P = 0.0017). The associated SNP is located in intron 10, which contains an alternate stop codon and may lead to decreased expression of the 130-kDa isoform, the isoform predicted to contain the O-GlcNAcase activity. We investigated whether this variant was responsible for the original linkage signal. The variance attributed to this SNP accounted for approximately 25% of the logarithm of odds. These results suggest that this variant within the MGEA5 gene may increase diabetes risk in Mexican Americans.