SPARC, an extracellular matrix protein, is identified as prognostic marker in interstitial lung diseases, including unclassifiable cases.
Immunohistochemical analysis showed that secreted protein acidic and rich in cysteine was strongly expressed in young fibrotic lung lesions but absent in older scars, according to a recent study.
Researchers applied spatial transcriptomics to examine molecular mechanisms underlying fibrosis in interstitial lung diseases (ILDs), a group of pulmonary disorders characterized by scarring and poor prognosis. Lung cryobiopsy specimens from five patients with various ILDs were examined, with high-dimensional weighted gene coexpression network analysis performed specifically on two cases rich in young fibrotic lesions. A distinct gene module, referred to as SM2, was identified in early fibrotic lesions. This module was associated with fibroblast activation and included hub genes COL1A1, COL1A2, COL3A1, and secreted protein acidic and rich in cysteine (SPARC).
To evaluate the clinical relevance of SPARC, the analysis, published in The Journal of Pathology, was extended to a cohort of 71 patients with unclassifiable ILDs. Quantitative assessment of SPARC expression showed that higher levels in either the upper or lower lung lobes were significantly associated with shorter overall survival. Multivariate models that adjusted for age, sex, and smoking history supported SPARC as an independent prognostic factor.
Additional integration with single-cell RNA sequencing datasets indicated that the SM2 module was enriched in specific fibroblast populations, including myofibroblasts and HAS1-high fibroblasts. These cell subsets are linked to extracellular matrix remodeling and exhibited signaling interactions with aberrant epithelial cells. The findings suggest that the SM2 module, and SPARC in particular, is involved in pathways related to fibrosis across multiple ILD subtypes, although the researchers noted that SPARC is not a novel molecule but rather a surrogate marker reflecting fibroblast activity.
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