Clinical significance of SPARC in esophageal squamous cell carcinoma

Chen, Yelong; Zhang, Ying; Tan, Yang; Liu, Zhaoyong

doi:10.1016/j.bbrc.2017.08.043

Cited by 15 publications

(14 citation statements)

References 16 publications

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“…However, most evidence supporting the role of SPARC in solid tumours is based on cancer cell-derived SPARC [17–19]. SPARC derived from different cellular origins is reported to be highly heterogeneous, and SPARC expressed by different cells may even lead to opposite clinical outcomes [20]. The confirmed effects and underlying mechanisms of GCAF-derived SPARC in gastric cancer remain to be demonstrated.…”

Section: Discussionmentioning

confidence: 99%

Low expression of SPARC in gastric cancer-associated fibroblasts leads to stemness transformation and 5-fluorouracil resistance in gastric cancer

Zhu

Chen

et al. 2019

Cancer Cell Int

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Background The aim of the present study was to clarify the correlations between SPARC expression in gastric cancer-associated fibroblasts (GCAFs) and the prognosis of patients with gastric cancer and to elucidate the role of GCAF-derived SPARC in stemness transformation and 5-fluorouracil resistance in gastric cancer. Methods One hundred ninety-two patients were enrolled in the present study. SPARC expression levels were evaluated by immunohistochemical staining. Primary GCAFs were obtained and cultured from cancer patients for in vitro study, and a lentivirus infection method was employed to knock down SPARC expression in GCAFs. The stemness phenotype and 5-fluorouracil (5-FU) response of gastric cancer cells were assessed via a 3D co-culture model. The apoptotic status and stemness alterations were monitored by flow cytometry and western blotting. Additionally, label-free quantification proteomics was used to identify the differentially expressed proteins and potential pathways in gastric cancer cells treated with GCAF-derived SPARC. Results Low expression of GCAF-derived SPARC was associated with decreased differentiation and reduced 5-year overall survival and was an independent predictive factor for prognosis in gastric cancer. The 3D tumour growth and 5-FU resistance abilities of gastric cancer cells were elevated after treatment with GCAFs with SPARC knockdown relative to these abilities in negative control cells. Additionally, suppressing SPARC expression in GCAFs facilitated the phenotypic alteration of gastric cancer cells towards CD44 + /CD24 − cancer stem cell (CSC)-like cells. Quantification proteomics analysis revealed that the differentially expressed proteins in gastric cancer cells were mainly involved in the AKT/mTOR and MEK/ERK signalling pathways. Conclusions SPARC expression in GCAFs is a useful prognostic factor in patients with gastric cancer. Low expression of GCAF-derived SPARC can lead to CSC transformation and 5-FU resistance. Additionally, the AKT/mTOR and MEK/ERK signalling pathways may participate in the malignant process. Electronic supplementary material The online version of this article (10.1186/s12935-019-0844-8) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Low expression of SPARC in gastric cancer-associated fibroblasts leads to stemness transformation and 5-fluorouracil resistance in gastric cancer

Zhu

Chen

et al. 2019

Cancer Cell Int

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“…SPARC is a matricellular protein that modulates cell adhesion and growth, along with cell-matrix interactions by binding to the extracellular matrix [33], and was suggested as a candidate biomarker for diagnosing invasive meningiomas [34]. Compared with the normal epithelium, the mRNA and protein expression levels of SPARC were found to be substantially higher in tumor tissues [35]. Moreover, overexpression of SPARC was correlated with a poor prognosis of patients with EAC [36].…”

Section: Discussionmentioning

confidence: 99%

Integrated Bioinformatics Analysis Identifies Hub Genes Associated with the Pathogenesis and Prognosis of Esophageal Squamous Cell Carcinoma

Zhang

Zhong

et al. 2019

BioMed Research International

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Esophageal squamous cell carcinoma (ESCC) accounts for over 90% of all esophageal tumors. However, the molecular mechanism underlying ESCC development and prognosis remains unclear, and there are still no effective molecular biomarkers for diagnosing or predicting the clinical outcome of patients with ESCC. Here, using bioinformatics analyses, we attempted to identify potential biomarkers and therapeutic targets for ESCC. Differentially expressed genes (DEGs) between ESCC and normal esophageal tissue samples were obtained through comprehensive analysis of three publicly available gene expression profile datasets from the Gene Expression Omnibus database. The biological roles of the DEGs were identified by Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Moreover, the Cytoscape 3.7.1 platform and subsidiary tools such as Molecular Complex Detection (MCODE) and CytoHubba were used to visualize the protein-protein interaction (PPI) network of the DEGs and identify hub genes. A total of 345 DEGs were identified between normal esophageal and ESCC samples, which were enriched in the KEGG pathways of the cell cycle, endocytosis, pancreatic secretion, and fatty acid metabolism. Two of the highest scoring models were selected from the PPI network using Molecular Complex Detection. Moreover, CytoHubba revealed 21 hub genes with a valuable influence on the progression of ESCC in these patients. Among these, the high expression levels of five genes—SPP1, SPARC, BGN, POSTN, and COL1A2—were associated with poor disease-free survival of ESCC patients, as indicated by survival analysis. Taken together, we identified that elevated expression of five hub genes, including SPP1, is associated with poor prognosis in ESCC patients, which may serve as potential prognostic biomarkers or therapeutic target for ESCC.

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“…SPARC has been suggested as a prognostic biomarker for certain cancers such as soft tissue sarcoma, esophageal SCC and glioblastoma since its expression correlates with poor survival (232)(233)(234). In addition, SPP1 may be prognostic for breast, lung, gastric, liver and colon cancers since it associated with tumor progression and decreased patient survival (235)(236)(237)(238).…”

Section: Mcps As Cancer Biomarkersmentioning

confidence: 99%

The Matrix Revolution: Matricellular Proteins and Restructuring of the Cancer Microenvironment

et al. 2020

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The extracellular matrix (ECM) surrounding cells is indispensable for regulating their behavior. The dynamics of ECM signaling are tightly controlled throughout growth and development. During tissue remodeling, matricellular proteins (MCPs) are secreted into the ECM. These factors do not serve classical structural roles, but rather regulate matrix proteins and cell-matrix interactions to influence normal cellular functions. In the tumor microenvironment, it is becoming increasingly clear that aberrantly expressed MCPs can support multiple hallmarks of carcinogenesis by interacting with various cellular components that are coupled to an array of downstream signals. Moreover, MCPs also reorganize the biomechanical properties of the ECM to accommodate metastasis and tumor colonization. This realization is stimulating new research on MCPs as reliable and accessible biomarkers in cancer, as well as effective and selective therapeutic targets. Research.

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Clinical significance of SPARC in esophageal squamous cell carcinoma

Cited by 15 publications

References 16 publications

Low expression of SPARC in gastric cancer-associated fibroblasts leads to stemness transformation and 5-fluorouracil resistance in gastric cancer

Low expression of SPARC in gastric cancer-associated fibroblasts leads to stemness transformation and 5-fluorouracil resistance in gastric cancer

Integrated Bioinformatics Analysis Identifies Hub Genes Associated with the Pathogenesis and Prognosis of Esophageal Squamous Cell Carcinoma

The Matrix Revolution: Matricellular Proteins and Restructuring of the Cancer Microenvironment

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