The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou 310006, China; Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Zhejiang Cancer Hospital, Hangzhou 310022, China.
The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou 310006, China.
Life Sci. 2023 Aug 1;326:121792. doi: 10.1016/j.lfs.2023.121792. Epub 2023 May 19.
We aim to explore the possibility and mechanism of SH3PXD2B as a reliable biomarker for gastric cancer (GC).
We used public databases to analyze the molecular characteristics and disease associations of SH3PXD2B, and KM database for prognostic analysis. The TCGA gastric cancer dataset was used for single gene correlation, differential expression, functional enrichment and immunoinfiltration analysis. SH3PXD2B protein interaction network was constructed by the STRING database. And the GSCALite database was used to explore sensitive drugs and perform SH3PXD2B molecular docking. The impact of SH3PXD2B silencing and over-expression by lentivirus transduction on the proliferation and invasion of human GC HGC-27 and NUGC-3 cells was determined.
The high expression of SH3PXD2B in gastric cancer was related to the poor prognosis of patients. It may affect the progression of gastric cancer by forming a regulatory network with FBN1, ADAM15 and other molecules, and the mechanism may involve regulating the infiltration of Treg, TAM and other immunosuppressive cells. The cytofunctional experiments verified that it significantly promoted the proliferation and migration of gastric cancer cells. In addition, we found that some drugs were sensitive to the expression of SH3PXD2B such as sotrastaurin, BHG712 and sirolimus, and they had strong molecular combination of SH3PXD2B, which may provide guidance for the treatment of gastric cancer.
Our study strongly suggests that SH3PXD2B is a carcinogenic molecule that can be used as a biomarker for GC detection, prognosis, treatment design, and follow-up.
本研究旨在探讨 SH3PXD2B 作为胃癌（GC）可靠生物标志物的可能性和机制。
我们使用公共数据库分析 SH3PXD2B 的分子特征和疾病相关性，并使用 KM 数据库进行预后分析。我们使用 TCGA 胃癌数据集进行单基因相关性、差异表达、功能富集和免疫浸润分析。通过 STRING 数据库构建 SH3PXD2B 蛋白相互作用网络。并使用 GSCALite 数据库探索敏感药物并进行 SH3PXD2B 分子对接。通过慢病毒转导沉默和过表达 SH3PXD2B 来确定其对人 GC HGC-27 和 NUGC-3 细胞增殖和侵袭的影响。
胃癌中 SH3PXD2B 的高表达与患者的不良预后相关。它可能通过与 FBN1、ADAM15 和其他分子形成调节网络来影响胃癌的进展，其机制可能涉及调节 Treg、TAM 和其他免疫抑制细胞的浸润。细胞功能实验验证了它能显著促进胃癌细胞的增殖和迁移。此外，我们发现一些药物如 sotrastaurin、BHG712 和 sirolimus 对 SH3PXD2B 的表达敏感，它们与 SH3PXD2B 具有很强的分子结合，这可能为胃癌的治疗提供指导。
我们的研究强烈表明 SH3PXD2B 是一种致癌分子，可作为 GC 检测、预后、治疗设计和随访的生物标志物。
