Wu Dali, Zhong Guanghui, Liu Yufeng, Li Cuilian, Yan Lingfei, Luo Yang, Li Qing, Liu Dawei, Wang Tao
Department of Urology, The Fifth Affiliated Hospital, Southern Medical University, Guangzhou, 510900, Guangdong, China.
Discov Oncol. 2025 Jun 11;16(1):1061. doi: 10.1007/s12672-025-02940-2.
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.
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.
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.
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.
研究表明，名为小G蛋白信号调节因子1（SGSM1）的蛋白质，它同时具有TBC结构域和RUN结构域，并与RAB和RAP介导的细胞信号传导相关，参与肿瘤进展。然而，尚不清楚SGSM1在泛癌发生发展中是否起关键作用。
利用癌症基因组图谱（TCGA）和基因型-组织表达（GTEx）数据库检测SGSM1在多种恶性肿瘤中的表达模式。在人类蛋白质图谱（HPA）和UALCAN数据库中验证SGSM1蛋白表达水平。使用STRING和GeneMANIA数据库的数据进行蛋白质-基因相互作用分析。通过K-M绘图仪和生存数据分析检验SGSM1表达的预测意义，包括总生存期（OS）、无进展生存期（PFI）和疾病特异性生存期（DSS）。为了进行与SGSM1相关的基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析，使用了R程序“clusterProfiler”。我们分析TISIDB数据库以寻找SGSM1表达与免疫或分子亚型之间的联系。此外，我们研究了SGSM1的表达与免疫相关基因的表达如何关联。
在TCGA中，SGSM1表达在绝大多数恶性肿瘤中下调，包括头颈部鳞状细胞癌（HNSC）、结肠癌（COAD）、乳腺癌（BRCA）和肾嫌色细胞癌（KIRP），并且在肾透明细胞癌（KIRC）、低级别胶质瘤（LGG）、间皮瘤（MESO）、胰腺癌（PAAD）和子宫内膜癌（UCEC）等癌症中提示预后不良。SGSM1的表达在分子和免疫癌症亚型中高度可变。在COAD、KIRC、PAAD和前列腺癌（PRAD）组织中，与正常组织相比，SGSM1蛋白下调。SGSM1预测的十种不同癌症的曲线下面积（AUC）大于0.7，表明具有相当程度的准确性。富集的KEGG通路中Ras信号通路占主导。发现在KIRC中SGSM1与免疫相关基因包括细胞毒性T淋巴细胞相关蛋白4（CTLA4）、程序性死亡蛋白1（PDCD1）、T细胞免疫球蛋白和ITIM结构域（TIGIT）、淋巴细胞激活基因3（LAG-3）和CD48存在负相关。
研究结果表明，SGSM1可作为多种肿瘤类型的新型生物标志物。SGSM1可能参与肿瘤免疫微环境，有望成为癌症的一种新型治疗靶点。
