Differential Gene Expression in SLAP Tears and Shoulder Instability- SOMOS 2025

c gerber, f say, j dobrich, b kowalski, c brunette, j johnson, z colburn, m bedrin, j galvin

Abstracted accepted for a rapid-fire presentation at the 2025 Society of Military Orthopaedic Surgeons Annual Meeting.

INTRODUCTION
Shoulder instability and superior labrum anterior-to-posterior (SLAP) tears are common causes of shoulder dysfunction that frequently necessitate surgical intervention. While the biomechanical distinctions between these conditions are well-established, the molecular mechanisms underlying their pathogenesis remain less clear. This observational, discovery-based study aimed to evaluate differential gene expression profiles in both whole blood and shoulder tissue of patients undergoing surgery for SLAP tears and shoulder instability. We hypothesized that these conditions would demonstrate distinct local inflammatory gene expression patterns, reflecting underlying differences in their molecular pathophysiology. 

METHODS
Patients aged 20–44 undergoing elective shoulder surgery for either SLAP tears (n=9) or shoulder instability (n=39) were prospectively enrolled at a single site. Whole blood samples were stabilized in DNA/RNA shield tubes, while excised shoulder tissue samples were snap-frozen immediately following surgical removal. RNA was extracted from blood and pulverized tissue. Gene expression was quantified using the nCounter Inflammatory Panel, targeting an array of pre-selected genes known to be associated with inflammation and tissue remodeling. Differential expression analysis was performed using the NanoStringDiff package for R, with statistical controls applied for potential confounders.

RESULTS
No statistically significant differences in gene expression were identified in whole blood samples between the SLAP tear and instability groups. In contrast, analysis of shoulder tissue revealed 62 genes with significantly altered expression. Of these, 40 genes were downregulated and 22 were upregulated in the SLAP tear group compared to the instability group. Notable differentially expressed genes included MMP3 (matrix metalloproteinase 3), involved in extracellular matrix degradation, and relaxin 2, implicated in tissue remodeling and inflammation.

DISCUSSION and CONCLUSION
The findings demonstrate that distinct local gene expression profiles are present in shoulder tissue of patients with SLAP tears compared to those with shoulder instability, suggesting differences in the underlying inflammatory and tissue remodeling processes. The lack of significant differences in whole blood supports the hypothesis that systemic markers may not sufficiently reflect localized pathophysiological differences. Furthermore, it emphasizes the need for local tissue sampling when evaluating molecular differences between these conditions. Differentially expressed genes such as MMP3 and relaxin 2 may serve as future targets for diagnostic or therapeutic strategies. Further studies with larger cohorts are warranted to validate these findings and assess the functional implications of these gene expression changes.