Osteoclast Stimulatory Transmembrane Protein (OCSTAMP) mRNA Levels and Clinical Variables in Persons with Plasma Cell Myeloma

Abstract

Background Bone disease is an important determinant of quality-of-life and survival of persons with plasma cell myeloma (PCM). Biomarkers of bone disease could be useful to predict risk and monitor therapy. In our prior analyses OCSTAMP (osteoclast stimulatory trans-membrane protein) mRNA levels were identified as increased above normals in persons with PCM. OCSTAMP encodes a membrane-anchored cell surface receptor promoting nucleation of osteoclasts involved in bone resorption and osteoclast differentiation.Aims Measure levels of OCSTAMP mRNA in subjects with PCM and interrogate clinical associations.Methods OCSTAMP mRNA levels were quantified by quantitative real-time polymerase chain reaction (RT-qPCR) in 224 bone marrow samples from 160 subjects with PCM including 160 newly-diagnosed; 55 in remission and 9 with recurrent PCM. Results were compared with 42 normals and data expressed as ratio of OSSTAMP mRNA/ABL mRNA. Associations with clinical variables were interrogated and comparisons analyzed using the Chi-square test.Results OCSTAMP mRNA levels were significantly greater than normals in 111 subjects (69%, [95% confidence interval l[CI], 62-77%], P<0.001) with newly-diagnosed PCM, in 5 (56% [23,88%]; P=0.39) relapsing after initial therapy and in 12 in remission (22% [11-33%; P<0.001). mRNA levels in samples from newly-diagnosed subjects (median, 0.52%; range, 0-121%) were significantly higher than in samples from subjects in remission (0.01%; range, 0-4.7%) or normals (0.02%; range, 0-0.10%; both p<0.001). Levels in subjects in remission and normals were similar (p=0.85). Median OCSTAMP mRNA level was used to dichotomize subjects into low (median 0.06%; range, 0-0.51%) and high (3.8%; range, 0.54-121%) cohorts (P<0.001). Subjects in the high cohort were more likely to be in Durie/Salmon stage-3 (p=0.035), to have serum albumin concentrations <35g/L (p=0.036), have serum C-reactive protein (CRP) concentrations ≥8mg/L (p=0.03) and have ≥1 pathological bone fractures (p=0.002).Conclusions OCSTAMP is highly transcribed in persons with newly-diagnosed and recurrent PCM compared with normals whereas persons in remission have similar levels to normals. OCSTAMP mRNA levels correlate with several clinical variables including Durie/Salmon stage, serum albumin C-reactive protein levels and likelihood of pathological bone fractures. OCSTAMP mRNA levels are potentially useful as a biomarker if our data are validated. DisclosuresNo relevant conflicts of interest to declare.