SGSM1 as a pan-cancer biomarker: multi-omics insights into immune regulation, prognostic value, and therapeutic implications

Abstract 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 piv...

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Main Authors: Dali Wu, Guanghui Zhong, Yufeng Liu, Cuilian Li, Lingfei Yan, Yang Luo, Qing Li, Dawei Liu, Tao Wang
Format: Article
Language:English
Published: Springer 2025-06-01
Series:Discover Oncology
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Online Access:https://doi.org/10.1007/s12672-025-02940-2
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Summary:Abstract 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.
ISSN:2730-6011