Objective:

To investigate the role of SPARC as a prognostic marker in interstitial lung diseases (ILDs) and its association with fibrosis.

Approach:

• Immunohistochemical Analysis: Examined SPARC expression in lung lesions of varying ages.
• Spatial Transcriptomics: Analyzed lung cryobiopsy specimens from five patients with ILDs to understand molecular mechanisms of fibrosis.
• Gene Coexpression Network Analysis: Performed on two cases with young fibrotic lesions to identify the SM2 gene module.
• Clinical Relevance Assessment: Extended analysis to a cohort of 71 patients with unclassifiable ILDs to evaluate SPARC expression and survival outcomes.

Key Findings:

• SPARC was strongly expressed in young fibrotic lung lesions but absent in older scars.
• The SM2 gene module associated with early fibrotic lesions included hub genes linked to fibroblast activation.
• Higher SPARC levels in lung lobes correlated with shorter overall survival in patients with unclassifiable ILDs.
• SPARC was identified as an independent prognostic factor after adjusting for age, sex, and smoking history.

Interpretation:

Limitations:

• The study is based on a limited number of patients (five for cryobiopsy and 71 for clinical relevance).
• SPARC is not a novel molecule but a surrogate marker.

Conclusion:

Sources:

• The Journal of Pathology