Key takeaways: The SPARC gene, which is an acronym for secreted protein, acidic, and rich cysteine, is significantly upregulated in mesothelioma patients, especially compared to other types of lung cancer patients. SPARC’s associated protein contributes to the growth and communication of the extracellular matrix (ECM) and cellular response to injury. When implicated with mesothelioma, upregulated SPARC contributes to local immunosuppression and worsened prognosis. Although there haven’t yet been any studies about treatments targeting SPARC, there could be in coming years.
The SPARC Gene
“SPARC” stands for the secreted protein, acidic, and rich in cysteine gene, and encodes for a protein of the same name. SPARC is located on human chromosome 5, and its protein-counterpart contributes to the durability, strength, and assembly of the extracellular matrix (ECM). The ECM is a complex conglomeration of sugars, proteins, collagens, and cellular signals that surrounds each bodily cell. The ECM is responsible for communicating information between cells, organizing cohesive growth, orchestrating planned cellular death (called apoptosis), among other complex functions. Besides contributing to the successful growth and maintenance of the ECM, SPARC production is upregulated after an injury; this is because SPARC proteins facilitate the changing of cell shapes, and consequently, the size of the spaces between cells. SPARC plays significant roles in the shapes, accessibility, growth, and recruitment of bodily cells, so it makes sense that SPARC is implicated in mesothelioma development.
The SPARC Gene and Mesothelioma
In most cases of mesothelioma, the SPARC gene is significantly upregulated. In fact, it has recently been established as a credible differentiator between mesothelioma and certain lung cancers (adenocarcinomas and squamous cell carcinoma). In Nakagiri et al.’s study, (2024) the researchers found that upregulated SPARC was found in 93.3% of epithelioid mesothelioma cases. By comparison, SPARC was only upregulated in 5% and 4.5% of lung adenocarcinomas and squamous cell carcinomas, respectively. This means that testing for SPARC can help doctors differentiate between mesothelioma and other cancers—which present in symptomatically and histologically similar ways—with accuracy. A characteristic of mesothelioma, like other cancers, is the ability of the cancer to usurp the normal anti-tumor capacities of the immune system. SPARC has been found to mediate the immunosuppression of mesothelioma tumors, meaning that genetic testing for SPARC upregulation could also help doctors stratify prognosis. Doctors and scientists already know that cell type, site of origin, and prior medical conditions are prognostic factors for mesothelioma patients. They hypothesized that genetic factors would contribute to prognosis, but now have quantifiable evidence that at least one gene might contribute to the conceptualization of a stratified prognosis.
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Future Considerations
Researchers have recently established that upregulated SPARC is a.) associated with mesothelioma over other lung cancers; b.) worse prognosis for mesothelioma patients; and c.) increased immunosuppression. Hopefully, new research will continue seeking to identify other genetic markers of mesothelioma so that gene therapy can be a feasible diagnostic and treatment model. There aren’t any treatments that downregulate SPARC yet, but there could be in coming years.
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Sources:
National Library Of Medicine 1
