Diagnostic and prognostic value of secreted protein acidic and rich in cysteine in the diffuse large B-cell lymphoma


Background: Secreted protein acidic and rich in cysteine (SPARC) is an extracellular matrix-associated protein. Studies have revealed that SPARC is involved in the cell interaction and function including proliferation, differentiation, and apoptosis. However, the role of SPARC in cancer is controversial, as it was reported as the promoter or suppressor in different cancers. Further, the role of SPARC in lymphoma is unclear.

Aim: To identify the expression and significance of SPARC in lymphoma, especially in diffuse large B-cell lymphoma (DLBCL).

Methods: The expression analysis of SPARC in different cancers was evaluated with Oncomine. The Brune, Eckerle, Piccaluga, Basso, Compagno, Alizadeh, and Rosenwald datasets were included to evaluate the mRNA expression of SPARC in lymphoma. The Cancer Genome Atlas (TCGA)-DLBCL was used to analyze the diagnostic value of SPARC in DLBCL. The Compagno and Brune DLBCL datasets were used for validation. Then, the diagnostic value was evaluated with the receiver operating characteristic (ROC) curve. The Kaplan-Meier plot was conducted with TCGA-DLBCL, and the ROC analysis was performed based on the survival time. Further, the overall survival analysis based on the level of SPARC expression was performed with the GSE4475 and E-TABM-346. The Gene Set Enrichment Analyses (GSEA) was performed to make the underlying mechanism-regulatory networks.

Results: The pan-cancer analysis of SPARC showed that SPARC was highly expressed in the brain and central nervous system, breast, colon, esophagus, stomach, head and neck, pancreas, and sarcoma, especially in lymphoma. The overexpression of SPARC in lymphoma, especially DLBCL, was confirmed in several datasets. The ROC analysis revealed that SPARC was a valuable diagnostic biomarker. More importantly, compared with DLBCL patients with low SPARC expression, those with higher SPARC expression represented a higher overall survival rate. The ROC analysis showed that SPARC was a favorable prognostic biomarker for DLBCL. Results of the GSEA confirmed that the high expression of SPARC was closely associated with focal adhesion, extracellular matrix receptor interaction, and leukocyte transendothelial migration, which suggested that SPARC may be involved in the regulation of epithelial-mesenchymal transition, KRAS, and myogenesis in DLBCL.

Conclusion: SPARC was highly expressed in DLBCL, and the overexpression of SPARC showed sound diagnostic value. More interestingly, the overexpression of SPARC might be a favorable prognostic biomarker for DLBCL, suggesting that SPARC might be an inducible factor in the development of DLBCL, and inducible SPARC was negative in some oncogenic pathways. All the evidence suggested that inducible SPARC might be a good diagnostic and prognostic biomarker for DLBCL.7