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Signal sequence receptor subunit 3: A novel indicator of immunosuppressive tumor microenvironment and clinical
Qin Hu1, Gujie Wu2, Huiyun Ma1
1Department of Respiratory Medicine, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226000, China; Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226000, China.
Background:
Signal sequence receptor subunit 3 (SSR3), a translocation-associated protein complex, plays a vital role in various diseases. However, its involvement in human cancers remains unclear.
Methods:
We conducted a comprehensive analysis by integrating data from multiple sources, including the Cancer Genome Atlas, Cancer Cell Lineage Encyclopedia, Genotype Tissue Expression, Human Protein Atlas, cBioPortal, TIMER, and ImmuCellAI. Additionally, we incorporated data from a clinical trial, two immunotherapy cohorts, and in vitro experiments to investigate SSR3's impact on cancer prognosis and immune response.
Results:
Our findings revealed a significant correlation between elevated SSR3 expression and unfavorable prognosis across various cancer types. Amplification is the most common genetic alteration in SSR3. Furthermore, functional enrichment analysis highlighted SSR3's regulatory role in promoting proliferation. In addition, SSR3 also serves as a pivotal mediator bridging the innate and adaptive immune systems and several related signaling pathways. Moreover, the correlation of SSR3 expression with tumor mutation burden in five cancer types, as well as with microsatellite instability in nine cancer types, suggests the potential of SSR3 as a predictive marker for immunotherapy response. To validate this hypothesis, we examined data from patients who underwent immunotherapy treatment. Our analysis revealed that individuals with low SSR3 expression demonstrated higher response rates to immune checkpoint inhibitors and longer overall survival compared to those with high SSR3 expression.
Conclusions:
Our study identifies SSR3 as a potential oncogene in humans, implicated in both tumorigenesis and cancer immunity. Elevated SSR3 expression is indicative of an immunosuppressive tumor microenvironment. Therefore, SSR3 holds promise as a potential prognostic biomarker and a target for immunotherapy in cancer treatment.
Insights
Signal sequence receptor subunit 3 (SSR3) is a potential oncogene linked to poor cancer prognosis and immune suppression. Lower SSR3 expression correlates with better immunotherapy response and survival, highlighting its potential as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Signal sequence receptor subunit 3 (SSR3) is a translocation-associated protein complex implicated in various diseases.
- Its specific role in human cancers has not been fully elucidated.
Purpose of the Study:
- To investigate the involvement of SSR3 in cancer development and its impact on patient prognosis.
- To explore the relationship between SSR3 expression and the tumor immune microenvironment.
- To assess SSR3 as a potential biomarker for immunotherapy response.
Main Methods:
- Integrated analysis of multi-omics data from TCGA, CCLE, GTEx, Human Protein Atlas, cBioPortal, TIMER, and ImmuCellAI.
- Inclusion of clinical trial and immunotherapy cohort data, alongside in vitro experiments.
- Correlation analysis of SSR3 expression with tumor mutation burden and microsatellite instability.
Main Results:
- Elevated SSR3 expression is significantly associated with unfavorable prognosis across multiple cancer types, with amplification being the most common genetic alteration.
- SSR3 promotes cancer cell proliferation and acts as a mediator between innate and adaptive immunity.
- Low SSR3 expression predicted higher response rates to immune checkpoint inhibitors and improved overall survival.
Conclusions:
- SSR3 functions as a potential oncogene in human cancers, influencing both tumorigenesis and anti-tumor immunity.
- High SSR3 expression indicates an immunosuppressive tumor microenvironment, suggesting its utility as a prognostic biomarker.
- SSR3 represents a promising therapeutic target for enhancing cancer immunotherapy outcomes.
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