ABSTRACT
BACKGROUND: In multiple myeloma (MM), impact of specific chromosomal translocations involving IgH (14q21 locus, including t(4;14), t(11;14), and t(14;16)) has been explored extensively. However, over 15% MM patients harboring IgH translocation with undefined partners have long been ignored. METHODS: A prospective non-randomized cohort study with a total of 715 newly-diagnosed MM cases was conducted, 13.6% of whom were t(14;undefined) positive. The whole cohort was divided into four groups: no IgH split (47.7%); t(14;undefined) (13.6%); t(11;14) (17.6%); and t(4;14) or t(14;16) group (21.1%). RESULTS: Median OS for the four groups was 84.2, not reached (NR), 58.7, and 44.2 months, respectively, with P values for t(14;undefined) vs no IgH split, t(11;14), and t(4;14)/t(14;16) groups of 0.197, 0.022, and 0.001, respectively. In bortezomib-based group, the survival advantage gained by t(14;undefined) group was much more significant compared to t(11;14) and t(4;14)/t(14;16) groups. Importantly, t(14;undefined) turned out to be an independent predictive factor for longer OS of MM patients in multivariate analysis, especially in the context of bortezomib treatment. Similar results were also observed in the PUMCH external validation cohort. CONCLUSION: Collectively, our data confirmed and externally validated the favorable prognosis of the t(14;undefined) groups, especially in the era of novel agents.
Subject(s)
Immunoglobulin Heavy Chains/genetics , Multiple Myeloma/genetics , Multiple Myeloma/mortality , Translocation, Genetic , Aged , Aged, 80 and over , Biomarkers, Tumor , Chromosomes, Human, Pair 11 , Chromosomes, Human, Pair 14 , Chromosomes, Human, Pair 16 , Chromosomes, Human, Pair 4 , Female , Gene Frequency , Humans , In Situ Hybridization, Fluorescence , Kaplan-Meier Estimate , Male , Middle Aged , Multiple Myeloma/diagnosis , Multiple Myeloma/therapy , Prognosis , Proportional Hazards ModelsABSTRACT
AIM: The changes in body composition and biomarker levels that occur during the aging process are complex and remain poorly understood. The present study aimed to evaluate changes in serum C-peptide levels and fat mass-to-lean mass ratio (FM/LM ratio) with increasing age, and to explore the associations between serum C-peptide levels and FM/LM ratio. METHODS: This was a population-based cross-sectional study that included 3912 participants aged 30-85 years. Body composition was measured using dual-energy X-ray absorptiometry. Analysis of covariance was used to evaluate how the serum C-peptide level and FM/LM ratio change with increasing age, as well as how the FM/LM ratio changes in line with increasing serum C-peptide level. A multiple linear regression analysis was carried out to determine the association between serum C-peptide level and FM/LM ratio. RESULTS: Analysis of covariance showed that serum C-peptide levels, and most regional FM/LM ratios tended to increase in line with increasing age. Total fat mass, total lean mass, percentage total fat mass and total FM/LM ratio were significantly elevated, and percentage total lean mass decreased significantly with increasing serum C-peptide levels in both men and women. Multiple linear regression analysis showed that serum C-peptide level was strongly associated with the total FM/LM ratio. CONCLUSIONS: The findings showed that both serum C-peptide level and FM/LM ratio increased with increasing age, and the serum C-peptide level was closely associated with changes in the total FM/LM ratio.