Published online Aug 6, 2021. doi: 10.12998/wjcc.v9.i22.6287
Peer-review started: April 25, 2021
First decision: May 24, 2021
Revised: May 29, 2021
Accepted: June 3, 2021
Article in press: June 3, 2021
Published online: August 6, 2021
Processing time: 93 Days and 13.3 Hours
Secreted protein acidic and rich in cysteine (SPARC), is a protein related to the extracellular matrix. Studies have shown that SPARC regulate cell interactions and display multi-functions, including proliferation, differentiation and apoptosis. However, the role of SPARC in cancer is controversial because it is reported to be a promoter or inhibitor in different cancers. In addition, the role of SPARC in lymphoma is unclear.
The role of SPARC in different cancers is controversial, and the expression and clinical application of SPARC in lymphoma is unclear.
This study aimed to explore the expression and clinical value of SPARC in lymphoma, especially in the diffuse large B-cell lymphoma (DLBCL).
The expression of SPARC in pan-cancer was conducted in Oncomine database. The Gene Expression Omnibus including Brune, Eckerle, Piccaluga, Basso, Compagno, Alizadeh, and Rosenwald datasets were subjected to confirm the expression of SPARC. The diagnostic value of SPARC was conducted in the Cancer Genome Atlas (TCGA)-DLBCL. The validated datasets were included with Compagno and Brune DLBCL datasets. Receiver operating characteristic (ROC) curve was applied to test the diagnostic value. The survival rate was conducted with Kaplan-Meier plot in TCGA-DLBCL database. The effect of SPARC on the overall survival was also confirmed in GSE4475 and E-TABM-346. The potential signaling pathways of SPARC in DLBCL was conducted with The Gene Set Enrichment Analyses (GSEA) software.
SPARC was highly expressed in pan-cancers, including brain and central nervous system cancer, breast cancer, colorectal cancer, esophageal cancer, gastric cancer, head and neck cancer, pancreatic cancer and sarcoma, most significantly in lymphoma. The overexpression of SPARC in lymphoma was confirmed by validated datasets. This study also identified that the overexpression of SPARC occurred significantly in DLBCL. And the overexpression of SPARC in DLBCL was tested in TCGA-DLBCL, and the ROC result showed a significant value of SPARC as a biomarker for DLBCL. Furthermore, the validation datasets including Compagno and Brune datasets confirmed the excellent diagnostic value of SPARC for DLBCL. In further prognostic analysis, DLBCL patients with high SPARC expression represented a favorable survival rate, and the ROC analysis of SPARC also demonstrated that SPARC as a favorable prognostic biomarker. The results of GSEA also revealed that SPARC was closely associated with focal adhesion, extracellular matrix receptor interaction and leukocyte transendothelial migration, which was involved in the regulation of epithelial-mesenchymal transition, KRAS and myogenesis signaling pathways in DLBCL.
SPARC was overexpressed in DLBCL, showing an excellent diagnostic value. Furthermore, the overexpression of SPARC could be a favorable prognostic biomarker. The inducible SPARC was also negatively correlated with some oncogenic pathways. Overall, the inducible SPARC could serve as a good diagnostic and prognostic biomarker for DLBCL.
This study identified that SPARC as a novel biomarker for the diagnosis and prognosis of DLBCL. Also, the inducible SPARC might be negatively correlated with some oncogenic pathways, suggesting that the inducible SPARC in the development of DLBCL could guide the clinical practice of DLBCL. However, this study was based on expression level, SPARC as a secreted protein, the serum level in DLBCL patients could be included in the further study.