Omics Overview of the SPARC Gene in Mesothelioma

Our plain-English summary of Omics Overview of the SPARC Gene in Mesothelioma, by L. Wu, M. de Perrot (Biomolecules, 2023).

The study

• Authors: L. Wu, M. de Perrot
• Journal: Biomolecules
• Published: 2023;13(7)
• Type of article: Review
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The SPARC gene plays multiple roles in extracellular matrix synthesis and cell shaping, associated with tumor cell migration, invasion, and metastasis. The SPARC gene is also involved in the epithelial-mesenchymal transition (EMT) process, which is a critical phenomenon leading to a more aggressive cancer cell phenotype. SPARC gene overexpression has shown to be associated with poor survival in the mesothelioma (MESO) cohort from the TCGA database, indicating that this gene may be a powerful prognostic factor in MESO. Its overexpression is correlated with the immunosuppressive tumor microenvironment. Here, we summarize the omics advances of the SPARC gene, including the summary of SPARC gene expression associated with prognosis in pancancer and MESO, the immunosuppressive microenvironment, and cancer cell stemness. In addition, SPARC might be targeted by microRNAs. Notably, despite the controversial functions on angiogenesis, SPARC may directly or indirectly contribute to tumor angiogenesis in MESO. In conclusion, SPARC is involved in tumor invasion, metastasis, immunosuppression, cancer cell stemness, and tumor angiogenesis, eventually impacting patient survival. Strategies targeting this gene may provide novel therapeutic approaches to the treatment of MESO.

In plain English

This article was a review by two authors in Toronto. It summarized published studies and online database information on the SPARC gene in mesothelioma (MESO), which the article describes as a rare cancer associated with asbestos exposure. It did not study asbestos exposure itself. The authors reported data from The Cancer Genome Atlas (TCGA). In the MESO cohort, higher SPARC expression was associated with poorer overall survival (log rank p = 3.6 times 10 to the minus 5) and poorer disease-free survival (log rank p = 0.023). The article did not state how many patients the cohort included. TCGA data also showed positive correlations in MESO between SPARC and infiltration by myeloid-derived suppressor cells and cancer-associated fibroblasts. They also showed positive correlations between SPARC and the TGF-β1 gene and its receptor gene, TGF-βR1. Two microRNAs, MIR193A and MIR652, were negatively correlated with SPARC and four other genes. The review also covered SPARC studies in other cancers, and described SPARC's role in blood-vessel growth as controversial. The authors concluded that SPARC may be an independent prognostic indicator for MESO and a promising therapeutic target. They noted that some mechanisms remain unknown.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Review, combined with the authors' own look-ups in online cancer gene databases (TCGA and related web tools)
• Who was studied: Mesothelioma (MESO) cohort and 32 cancer types (pancancer) in the TCGA database, plus published studies. The number of patients is not stated.
• Exposure: No asbestos or fiber exposure was studied. The subject was expression of the SPARC gene in tumors. Asbestos is mentioned only as background on mesothelioma.
• Main results:
  • In the TCGA MESO cohort, higher SPARC expression was associated with poorer overall survival (log rank p = 3.6 times 10 to the minus 5) and poorer disease-free survival (log rank p = 0.023).
  • TCGA data showed a strong positive correlation in MESO between SPARC expression and infiltration by myeloid-derived suppressor cells (MDSCs).
  • TCGA data showed a strong positive correlation in MESO between SPARC expression and infiltration by cancer-associated fibroblasts (CAFs).
  • TCGA data showed a strong positive correlation in MESO and other cancer types between SPARC expression and expression of TGF-β1 and its receptor gene TGF-βR1.
  • In TCGA, SPARC expression correlated significantly with 97 microRNAs. MIR193A and MIR652 were negatively correlated with five EMT genes, including SPARC.
• The authors' conclusion: The authors concluded that SPARC is a critical EMT marker of MESO whose overexpression is highly associated with poor prognosis. They concluded it may be an independent prognostic indicator for MESO and a promising therapeutic target.
• Limitations the authors state:
  • The authors state it is unknown whether SPARC promotes mesothelioma cell stemness.
  • The authors state the mechanism by which SPARC leads to EMT in MESO is not fully understood.
  • The authors state there are no studies so far on MESO-specific EMT markers and their related microRNA genes.
  • The authors describe SPARC's role in angiogenesis as controversial and still open.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Metastasis, Tumor Microenvironment, Prognosis, Angiogenesis.

Related studies

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• A panel of emerging EMT genes identified in malignant mesothelioma — L. Wu, S. Amjad, et al. (2022)
• A comprehensive investigation on pan-cancer impacts of constitutive centromere associated network gene family by integrating multi-omics data: A CONSORT-compliant article — H. Su, Y. Fan, et al. (2022)
• Micro-RNA-215 and -375 regulate thymidylate synthase protein expression in pleural mesothelioma and mediate epithelial to mesenchymal transition — F. Napoli, I. Rapa, et al. (2022)
• CDKN2A, NF2, and JUN are dysregulated among other genes by miRNAs in malignant mesothelioma -A miRNA microarray analysis — M. Guled, L. Lahti, et al. (2009)
• Gene and MicroRNA Perturbations of Cellular Response to Pemetrexed Implicate Biological Networks and Enable Imputation of Response in Lung Adenocarcinoma — E.R. Gamazon, M.R. Trendowski, et al. (2018)

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