GSE194108
A preliminary, observational study using whole-blood RNA sequencing reveals differential expression of inflammatory and bone markers post-implantation of percutaneous osseointegrated prostheses
While the benefits of direct skeletal attachment of artificial limbs are well recognized, device failure due to infection and insufficient osseointegration remain obstacles to obtaining consistent, successful outcomes. Currently, the potential for device failure is assessed by clinical, radiographic evidence of bone atrophy, the presence of radiolucent lines at the bone-implant interface, and subjective pain and function scores. Our hypothesis is that measurable biological indices might add an objective means to assess trends toward bone and stomal healing. This longitudinal cohort study was undertaken to identify potential serological biomarkers suggestive of bone remodeling and the presence of stomal tissue inflammation. Ten unilateral transfemoral amputee Veterans, who were implanted with a percutaneous osseointegration (OI) system, were recruited to participate in this IRB-approved study. Venous blood samples were obtained from before the Stage 1 Surgery up to 1 year following the Stage 2 Surgery. Whole-blood RNA was extracted, sequenced, mapped, and analyzed. Of the significant differentially expressed (DEGs) genes (p<0.05) identified, four genes (IL12B, IL33, COL2A1, and SOST) were validated using qPCR. Enrichment analysis was performed to identify significant (p<0.01) Gene Ontology (GO) terms. Most DEGs were only detected at PoS1 immediately after the first surgery. Four significant genes identified, IL12B and IL33, related to inflammation, and COL2A1 and SOST associated with bone remodeling were identified with greater than 20 log fold-change. Whole-blood RNA-seq data from 10 patients who previously underwent percutaneous osseointegrated lower limb implantation revealed four genes of interest that are known to be involved in inflammation or bone remodeling. If verified in future studies, these genes may serve as markers for predicting optimal bone remodeling and stomal tissue healing following OI implantation. Overall design: Whole-blood samples were collected from patients before their first surgery and up to 12 months after their second surgery. A total of 97 samples were collected. Please note that the values in the 'characteristics: time point' represent: PrS: pre-surgery PoS: post-surgery W: week M: month For example, PoS2-W2 means post-surgery 2 week 2.