Downregulation of SPARC Is Associated with Epithelial-Mesenchymal Transition and Low Differentiation State of Biliary Tract Cancer Cells

Aghamaliyev, Ughur; Gaitantzi, H; Thomas, Maria; Simon-Keller, Katja; Gaiser, Timo; Marx, Alexander; Yagublu, Vugar; Araos, Joaquín; Cai, Chen; Valous, Nektarios A.; Halama, Niels; Kiesslich, Tobias; Ebert, Matthias P.; Grützmann, Robert; Rückert, Felix; Breitkopf‐Heinlein, Katja

doi:10.1159/000494734

Cited by 8 publications

(4 citation statements)

References 36 publications

(45 reference statements)

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“…Previous studies have indicated that the expression of SPARC in gastric cancer is correlated with the expression of E-cadherin, Slug and Vimentin, and the positive expression of SPARC is negatively correlated with the survival rate of patients with gastric cancer. Positive expression of E-cadherin is positively correlated with the survival rate of patients with gastric cancer ( 7 ). At the same time, it has been indicated that SPARC may affect the metastasis of lung cancer through the Wnt/β-catenin signaling pathway.…”

Section: Introductionmentioning

confidence: 99%

Prognostic significance of SPARC expression in non‑small cell lung cancer: A meta‑analysis and bioinformatics analysis

Shi

Zhang

et al. 2022

Oncol Lett

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The aim of the present study was to elucidate the significance of secreted protein acidic and cysteine rich (SPARC) expression in non-small cell lung cancer (NSCLC) in terms of clinicopathology, immune-cell infiltration and survival prognosis. A meta-analysis and bioinformatics analysis were performed using studies retrieved with PubMed, Web of Science, Wanfang Data and the Chinese National Knowledge Infrastructure databases. The meta-analysis suggested that, compared with normal tissues, SPARC expression was elevated in NSCLC tissues. The expression of SPARC was not significantly associated with TNM stage and lymph-node metastasis, and was positively associated with patient gender. Regarding the differential expression of SPARC and the relationship between expression levels and survival, the Oncomine database was consulted and Kaplan-Meier curves were drawn. It was indicated that SPARC mRNA expression levels were higher in NSCLC tissues than in normal tissues. Low expression of SPARC mRNA was negatively associated with overall survival, first progression survival and post-progression survival of patients. Further exploration of the relationship between SPARC expression and survival by univariate analysis indicated that TNM stage, lymph node metastasis, distant metastasis and depth of infiltration of lung cancer were negatively associated with patient prognosis. Cox multifactorial analysis suggested that SPARC expression levels and TNM stage were risk factors significantly affecting the prognosis of patients with NSCLC. Analysis with the GEPIA and UALCAN databases further indicated that the mRNA expression level of SPARC in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) was higher than that in normal lung tissue, and the SPARC expression levels were affected by factors such as the TNM stage of lung cancer.A lower the level of SPARC mRNA expression was associated with a better relative survival prognosis of patients. In the Human Protein Atlas database, the expression level of SPARC protein was higher in LUAD and LUSC than in normal lung tissue. In the Timer database, the expression level of SPARC was closely linked to immune cells related to the occurrence of lung cancer, and the degree of immune-cell infiltration and SPARC protein expression were closely related to the prognosis of patients with lung cancer. Immune cells were indicated to exhibit significant inhibition of DNA proliferation mutation mechanisms in lung cancer (P<0.05). In summary, SPARC expression may be used as a valuable indicator of prognosis in patients with NSCLC, which may provide new approaches for preventative treatment.

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Section: Introductionmentioning

confidence: 99%

Prognostic significance of SPARC expression in non‑small cell lung cancer: A meta‑analysis and bioinformatics analysis

Shi

Zhang

et al. 2022

Oncol Lett

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“…In addition, Deng et al confirmed that the SPARC content is increased in CCA tissues and cells, and SPARC elevated CCA cell proliferation, metastasis, and EMT [30]. In addition, a lack of SPARC was linked with EMT and low differentiation conditions in biliary tract cancer [31]. However, Hu et al showed that SPARC upregulation in M2-type macrophages can inhibit M2-mediated promotion of growth, migration and antiapoptotic effects in gastric cancer (GC).…”

Section: Discussionmentioning

confidence: 99%

SPARC induces M2 polarization of macrophages to promote proliferation, migration, and angiogenesis of cholangiocarcinoma cells

Deng¹,

Yun²,

Yan³

et al. 2022

neo

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Cholangiocarcinoma (CCA) is a disease that includes a variety of epithelial neoplasms characterized by the differentiation of cholangiocytes. M2 polarization is imperative to the development of CCA cells. In this study, we investigated the influence of secreted protein acidic and rich in cysteine (SPARC) on M2 polarization and CCA cell growth. We found that the SPARC level was amplified in M2-polarized macrophages and TAMs. In addition, the downregulation of SPARC prevented the M2 polarization of macrophages. Silencing SPARC inhibited the M2 macrophage-mediated effects on the proliferation, migration, and angiogenesis of CCA cells.Additionally, SPARC knockdown blocked the M2 polarization of macrophages by inhibiting the PI3K/AKT signaling. Moreover, an activator of PI3K signaling repressed the effect of SPARC knockdown on the M2 macrophage-induced elevation of proliferation, migration, and angiogenesis in CCA cells. In conclusion, SPARC contributes to the M2 polarization of macrophages to promote proliferation, migration, and angiogenesis of CCA cells, which provides new insight into the treatment of CCA.

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“…Studies showed that SPARC expression can be induced remarkably with the development of lung, esophageal, pancreatic, and prostate cancer, suggesting that SPARC could be a tumor promoter[ 5 - 9 ]. In detail, mechanism studies revealed that SPARC regulated the tumor growth factor β (TGF-β) signaling and then promoted the epithelial-mesenchymal transition (EMT), which participates in the cancer metastasis[ 5 , 10 , 11 ]. SPARC was a tumor promoter to activate the phosphatidylinositol 3-phosphate kinase (PI3K)/AKT pro-oncogenic pathway[ 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

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

Pan¹,

Liu²

2021

WJCC

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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.

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Downregulation of SPARC Is Associated with Epithelial-Mesenchymal Transition and Low Differentiation State of Biliary Tract Cancer Cells

Cited by 8 publications

References 36 publications

Prognostic significance of SPARC expression in non‑small cell lung cancer: A meta‑analysis and bioinformatics analysis

Prognostic significance of SPARC expression in non‑small cell lung cancer: A meta‑analysis and bioinformatics analysis

SPARC induces M2 polarization of macrophages to promote proliferation, migration, and angiogenesis of cholangiocarcinoma cells

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

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