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

Abstract

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.

Hypoxia-related tumor environment correlated with immune infiltration and therapeutic sensitivity in diffuse large B-cell lymphoma

“…Single DLBCL cells play a role in adhesion to adjacent mesenchymal stromal cells and extracellular matrix (Dus-Szachniewicz et al, 2018). Pan et al reported the extracellular matrix-associated protein SPARC was highly expressed in DLBCL and might be a favorable prognostic biomarker for DLBCL (Pan and Liu, 2021). In addition, fibroblast and extracellular matrix components which represent stromal genetic signatures are associated with good survival in DLBCL (Haro and Orsulic, 2018).…”

Identification of Hub Genes and Key Pathways Associated with Follicular Lymphoma

“…e multivariate Cox analysis revealed that lower FAK expression may be an independent predictor of poor disease outcomes [19]. Furthermore, another study reported that leukocyte transendothelial migration, ECMreceptor interaction, and focal adhesion were implicated in the development of diffuse large B-cell lymphoma [20].…”

Dual delivery of carbon monoxide and doxorubicin using haemoglobin–albumin cluster: proof of concept for well-tolerated cancer therapy

“…38 In addition, albumin is known to pass through the endothelial barrier at the tumour site via albumin-binding proteins such as Gp60. 39,40 Since tumour tissues consume a great deal of nutrients and energy during the rapid growth of tumour cells, albumin appears to be taken up as a source of nutrients via albumin-binding proteins. 40 Therefore, CO-HemoAct-DOX, whose surface was covered by albumin, with a core haemoglobin load (CO), could be effectively delivered to tumour tissues by enhancing the EPR effect and uptake via Gp60, leading to high anti-tumour activity.…”