研究概要
SGSM2可能不仅是预后评估的重要指标,还可能是开发新治疗方法的关键靶点,为UVM患者的治疗提供新视角。
研究思路结论见上方概要
背景
小G蛋白信号调节因子2(SGSM2)的异常表达与甲状腺癌和乳腺癌的发生有关。然而,SGSM2在葡萄膜黑色素瘤(UVM)中的作用尚不清楚。目的:为阐明这一不确定性,我们的研究采用了生物信息学分析和实验验证。
方法
通过定量实时PCR(qRT-PCR)检测UVM细胞系中SGSM2的表达。我们利用癌症基因组图谱(TCGA)数据库评估SGSM2表达与临床特征的关系及其在UVM中的预后意义。此外,该研究还探讨了SGSM2在UVM中与免疫浸润、免疫检查点基因、微卫星不稳定性(MSI)和药物敏感性相关的潜在调控网络。该研究还检测了UVM单细胞测序数据中SGSM2的表达。
结果
SGSM2在UVM细胞系中高表达。此外,UVM患者中SGSM2水平升高与较差的总生存期(OS)(p < 0.001)、无进展生存期(PFS)(p < 0.001)和疾病特异性生存期(DSS)(p < 0.001)显著相关。此外,SGSM2表达被确定为UVM患者的独立预后因素(p < 0.001)。SGSM2与多个通路相关,包括钙信号通路、NK 细胞介导的细胞毒性、细胞黏附分子(CAMs)等。该研究揭示,UVM中SGSM2表达与免疫浸润、免疫检查点基因和MSI相关。此外,在UVM患者中观察到SGSM2表达与化合物GSK690693、TL-2-105、PHA-793887、Tubastatin A和SB52334之间存在显著的负相关。
展开英文摘要原文
BACKGROUND: The abnormal expression of small G protein signaling modulator 2 (SGSM2) is related to the occurrence of thyroid cancer and breast cancer. However, the role of SGSM2 in uveal melanoma (UVM) is unclear.
OBJECTS: To elucidate this ambiguity, our study utilized bioinformatics analysis and experimental validation.
METHODS: The expression of SGSM2 was detected in UVM cell lines through quantitative real-- time PCR (qRT-PCR). We utilized the Cancer Genome Atlas (TCGA) database to assess the relationship between SGSM2 expression and clinical characteristics, as well as its prognostic significance in UVM. Furthermore, the study examined potential regulatory networks involving SGSM2 in relation to immune infiltration, immune checkpoint genes, microsatellite instability (MSI), and drug sensitivity in UVM. The study also examined SGSM2 expression in UVM single-cell sequencing data.
RESULTS: SGSM2 was highly expressed in UVM cell lines. Moreover, elevated levels of SGSM2 in UVM patients were significantly linked to poorer overall survival (OS) (p < 0.001), progress- free survival (PFS) (p < 0.001), and disease-specific survival (DSS) (p < 0.001). Additionally, SGSM2 expression was identified as an independent prognostic factor in UVM patients (p < 0.001). SGSM2 was associated with several pathways, including the calcium signaling pathway, natural killer cell-mediated cytotoxicity, cell adhesion molecules (CAMs), and others. The study revealed that SGSM2 expression in UVM is linked to immune infiltration, immune checkpoint genes, and MSI. Additionally, a significant inverse correlation was observed between SGSM2 expression and the compounds GSK690693, TL-2-105, PHA-793887, Tubastatin A, and SB52334 in UVM patients.
CONCLUSION: SGSM2 may not only serve as an important indicator for prognostic assessment. Still, it may also be a key target for the development of new therapeutic approaches, providing new perspectives on the treatment of UVM patients.
论文信息
- 作者
- Liang D、Zhang Q、Pang Y、Yan R、Ke Y
- 单位
- Department of Ophthalmology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, Guangdong, China.China
- 期刊
- Protein and peptide letters2024