Li Houqiang, Zheng Lanqing, Zhang Xia, Yu Xunbin, Zhong Guodong, Chen Xiaoyan, Chen Xin, Chen Linying
Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian 350001, P.R. China.
Department of Pathology, Fuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian 350001, P.R. China.
Oncol Lett. 2024 Oct 17;29(1):8. doi: 10.3892/ol.2024.14754. eCollection 2025 Jan.
SH3 domain-binding glutamic acid-rich protein-like 3 (SH3BGRL3) is involved in several human cancers. However, its relationship with gastric cancer (GC) remains elusive. Multiple online bioinformatic tools were used to evaluate the messenger (m)RNA expression levels of SH3BGRL3 in GC using data from The Cancer Genome Atlas and Gene Expression Omnibus databases. Reverse transcription-quantitative PCR and tissue microarray-based immunohistochemistry were performed to assess SH3BGRL3 expression in relation to clinicopathological parameters and outcomes in patients with GC. Significant differentially expressed genes (DEGs) of SH3BGRL3 were enriched and visualized. Furthermore, associations between the expression of SH3BGRL3 and the infiltration of immune cells were explored. SH3BGRL3 exhibited aberrant expression in tumor tissues compared with adjacent normal tissues at the mRNA and protein expression levels, especially in Epstein-Barr virus-negative GC (EBVnGC). Higher SH3BGRL3 expression was significantly associated with increasing tumor-node-metastasis staging, tumor budding, perineural invasion, EGFR expression, and a notably higher preoperative blood glucose concentration in clinical specimens. Multivariate analysis revealed that higher SH3BGRL3 expression was an independent adverse prognostic factor for the overall survival of patients with EBVnGC (hazard ratio, 1.666; P=0.018). Furthermore, the stratified analysis revealed that the SH3BGRL3 phenotype could help to refine prognosis in patients. The C-index of the nomogram was 0.740 when combining SH3BGRL3 with other clinicopathological parameters, which indicated a good model for clinical follow-up decisions. Gene functional enrichment analysis also revealed that the DEGs of SH3BGRL3 were mainly enriched in regulating ATP metabolism, ATP synthesis, oxidative phosphorylation and the electron transport chain in GC. Moreover, a higher SH3BGRL3 expression was significantly positively correlated with the infiltrating macrophages in GC. In conclusion, SH3BGRL3 is upregulated in GC, particularly in EBVnGC. Higher SH3BGRL3 expression is closely associated with hyperglycemia and poor outcomes in patients with EBVnGC, suggesting its potential as a biomarker and prognostic predictor.
SH3结构域结合富含谷氨酸蛋白样3（SH3BGRL3）与多种人类癌症相关。然而，其与胃癌（GC）的关系仍不明确。利用来自癌症基因组图谱（The Cancer Genome Atlas）和基因表达综合数据库（Gene Expression Omnibus）的数据，使用多种在线生物信息学工具评估SH3BGRL3在胃癌中的信使核糖核酸（mRNA）表达水平。进行逆转录定量聚合酶链反应和基于组织芯片的免疫组织化学分析，以评估SH3BGRL3表达与胃癌患者临床病理参数及预后的关系。对SH3BGRL3的显著差异表达基因（DEG）进行富集和可视化分析。此外，还探讨了SH3BGRL3表达与免疫细胞浸润之间的关联。在mRNA和蛋白质表达水平上，与相邻正常组织相比，SH3BGRL3在肿瘤组织中呈现异常表达，尤其是在爱泼斯坦-巴尔病毒阴性胃癌（EBVnGC）中。SH3BGRL3表达升高与临床标本中肿瘤-淋巴结-转移分期增加、肿瘤芽生、神经周围浸润、表皮生长因子受体（EGFR）表达以及术前血糖浓度显著升高显著相关。多变量分析显示，SH3BGRL3表达升高是EBVnGC患者总生存的独立不良预后因素（风险比，1.666；P=0.018）。此外，分层分析显示，SH3BGRL3表型有助于细化患者的预后。当将SH3BGRL3与其他临床病理参数结合时，列线图的C指数为0.740，这表明该模型可用于临床随访决策。基因功能富集分析还显示，SH3BGRL3的DEG主要富集于胃癌中调节ATP代谢、ATP合成、氧化磷酸化和电子传递链。此外，SH3BGRL3表达升高与胃癌中浸润性巨噬细胞显著正相关。总之，SH3BGRL3在胃癌中上调，尤其是在EBVnGC中。SH3BGRL3表达升高与EBVnGC患者的高血糖和不良预后密切相关，提示其作为生物标志物和预后预测指标的潜力。
