SPARC is a Novel Prognostic Biomarker for Ovarian Cancer and Associated with Immune Signatures and Drug Response

Abstract

Background: The calcium-binding matricellular glycoprotein (SPARC, secreted protein, acidic and rich in cysteine) belongs to the extracellular-matrix-protein family, and its functions mainly focus on tissue injury, remodeling, and tumorigenesis. The role of SPARC in ovarian cancer remains controversial at present. Methods: We searched SPARC using The Cancer Genome Atlas/Genotype-Tissue Expression (TCGA/GTEx) and other databases to analyze the relationship between its expression level and survival, immunity signatures, and chemical drug response, in ovarian cancer. Additionally, we overexpressed SPARC with plasmids in ovarian cancer SKOV3 and ID8 cell lines, then measured the effects of SPARC on the proliferation, migration, invasiveness, clonality, and stemness of ovarian cancer cells by Cell Counting Kit-8 (CCK8), Transwell, wound healing assay, adhesion assay, plate cloning assay, and soft agar spheroid formation in vitro. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed the potential signaling pathway for SPARC. Results: The higher expression of SPARC in ovarian cancer is related to more advanced tumor stage, poorer clinical survival, and worse chemical drug response, whereas it is positively correlated with immune signatures. For ovarian cancer phenotypes, higher SPARC expression level promotes cell proliferation, migration, colony formation, and spheroid formation. The GO and KEGG enrichment highlighted the potential molecular mechanisms for SPARC with PI3K-AKT and MAPK signaling regulation. Conclusions: SPARC promotes ovarian cancer progression through proliferation, migration, invasiveness, clonality, and stemness. A high level of expression of SPARC in ovarian cancer patients can be used as a marker of poor prognosis and poor drug response.

Keywords

• drug response
• immune cell infiltration
• metastasis
• ovarian cancer
• sparc