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SGSM1 as a pan-cancer biomarker: multi-omics insights into immune regulation, prognostic value, and therapeutic
Dali Wu1, Guanghui Zhong1, Yufeng Liu1
1Department of Urology, The Fifth Affiliated Hospital, Southern Medical University, Guangzhou, 510900, Guangdong, China.
Background:
It has been shown that the protein known as Small G Protein Signaling Modulator 1 (SGSM1), which has both a TBC domain and RUN domain and was linked to RAB- and RAP-mediated cellular signaling, is involved in the advancement of tumors. It is unclear, however, whether SGSM1 is pivotal in the development of pan-cancer.
Methods:
The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases were used to examine the expression patterns of SGSM1 in a variety of malignancies. The SGSM1 protein expression levels were validated in the HPA and UALCAN databases. Protein-gene interaction analysis was carried out using data from the STRING and GeneMANIA databases. The predictive significance of SGSM1 expression was examined via the K-M plotter and survival data analyses and included OS, PFI, and DSS. For the purpose of conducting SGSM1-related GO and KEGG enrichment analyses, the R program "clusterProfiler" was utilized. We analyzed the TISIDB database in search of links between SGSM1 expression and immune or molecular subtypes. In addition, we examined how the expression of SGSM1 is linked to that of immune-related genes.
Results:
In TCGA, SGSM1 expression was shown to be downregulated in the vast majority of malignancies, including HNSC, COAD, BRCA, and KIRP, and to indicate an unfavorable prognosis in cancers such as KIRC, LGG, MESO, PAAD, and UCEC. The expression of SGSM1 is highly variable across molecular and immunological cancer subtypes. In COAD, KIRC, PAAD, and PRAD tissues, the SGSM1 protein was downregulated in comparison with normal tissue. The AUC for ten different cancers predicted by SGSM1 was more than 0.7, indicating a considerable degree of accuracy. The Ras signaling pathway dominated the enriched KEGG pathways. SGSM1 in KIRC was discovered to have a negative link to immune-related genes, including CTLA4, PDCD1, TIGIT, LAG-3, and CD48.
Conclusions:
The findings demonstrated that SGSM1 could be used as a novel biological marker for a wide variety of tumor types. SGSM1 may be implicated in the tumor immune microenvironment, which holds promise as a putative novel treatment target for cancer.
Insights
Small G Protein Signaling Modulator 1 (SGSM1) is downregulated in most cancers and linked to poor prognosis. This protein may serve as a novel pan-cancer biomarker and potential therapeutic target, especially concerning the tumor immune microenvironment.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Small G Protein Signaling Modulator 1 (SGSM1) possesses TBC and RUN domains and influences RAB/RAP-mediated signaling.
- SGSM1's role in tumor progression is recognized, but its pan-cancer significance remains unclear.
Purpose of the Study:
- To investigate the role of SGSM1 in pan-cancer development.
- To evaluate SGSM1 as a potential pan-cancer biomarker and therapeutic target.
Main Methods:
- Utilized TCGA and GTEx databases for SGSM1 expression analysis across various cancers.
- Validated protein levels using HPA and UALCAN databases.
- Assessed protein-gene interactions via STRING and GeneMANIA.
- Analyzed prognostic significance using K-M plotter and survival data (OS, PFI, DSS).
- Performed GO and KEGG enrichment analyses using R's clusterProfiler.
- Investigated SGSM1 correlations with immune/molecular subtypes and immune genes via TISIDB.
Main Results:
- SGSM1 was downregulated in most cancers (e.g., HNSC, COAD, BRCA, KIRP) and associated with unfavorable prognosis (e.g., KIRC, LGG, MESO, PAAD, UCEC).
- SGSM1 expression varied significantly across molecular and immunological subtypes.
- Protein levels were lower in COAD, KIRC, PAAD, and PRAD tumor tissues compared to normal.
- SGSM1 demonstrated predictive accuracy (AUC > 0.7) for ten cancers.
- Enriched KEGG pathways included the Ras signaling pathway.
- SGSM1 negatively correlated with immune-related genes (e.g., CTLA4, PDCD1) in KIRC.
Conclusions:
- SGSM1 shows potential as a novel pan-cancer biomarker.
- SGSM1's involvement in the tumor immune microenvironment suggests it as a promising therapeutic target.
