Gene expression signatures predict response to therapy with growth hormone

Abstract

Recombinant human growth hormone (r-hGH) is used as a therapeutic agent for disorders of growth including growth hormone deficiency (GHD) and Turner syndrome (TS). Treatment is costly and current methods to model response are inexact. GHD (n = 71) and TS patients (n = 43) were recruited to study response to r-hGH over 5 years. Analysis was performed using 1219 genetic markers and baseline (pre-treatment) blood transcriptome. Random forest was used to determine predictive value of transcriptomic data associated with growth response. No genetic marker passed the stringency criteria for prediction. However, we identified an identical set of genes in both GHD and TS whose expression could be used to classify therapeutic response to r-hGH with a high accuracy (AUC > 0.9). Combining transcriptomic markers with clinical phenotype was shown to significantly reduce predictive error. This work could be translated into a single genomic test linked to a prediction algorithm to improve clinical management. Trial registration numbers: NCT00256126 and NCT00699855.

Significant biomarkers for predicting 1-month changes in IGF-1 in growth hormone-deficient children following r-hGH therapy

“…Notably, SNP rs12882504 of SOS2 and probe 237640_at of VCPKMT are relatively close in position on the chromosome, and VCPKMT is a methyltransferase that trimethylates VCP Lys-315. As reported, the level of VCP methylation is positively correlated with the growth response in GHD patients [10] and with a marked reduction in growth development in VCPKMTdeficient cells, indicating that VCPKMT may affect the GHD response and that SOS2 may play a regulatory role. In summary, we successfully established a novel and promising model through the elastic net algorithm and identified significant biomarkers for the prediction of 1-month ΔIGF-1 in GHD children following r-hGH therapy, which can aid in clinical judgement for medical professionals.…”