整合素β5 是一种无创性的诊断生物标志物，与胃癌的不良预后和免疫治疗疗效相关。
Integrin β5, a noninvasive diagnostic biomarker, is associated with unfavorable prognosis and immunotherapy efficacy in gastric cancer.
机构信息
Department of Clinical Laboratory, Harbin Medical University Cancer Hospital, Harbin, 150081, China.
Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, 150081, China.
出版信息
BMC Gastroenterol. 2024 Oct 11;24(1):362. doi: 10.1186/s12876-024-03447-w.
BACKGROUND
Integrin β5 (ITGB5) is a pivotal player in the pathogenesis of gastric cancer (GC). We aimed to explore the potential value of ITGB5 as a predictor of diagnosis and immunotherapy in gastric cancer.
METHODS
The expression of ITGB5 in GC was assessed using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and verified through quantitative polymerase chain reaction (qPCR) and immunohistochemistry. Kaplan-Meier curves were conducted to evaluate the prognostic significance. The immune cells infiltration, tumor mutational burden (TMB), and immunophenoscore (IPS) were examined using CIBERSORT, TIMER, and TISIDB. In addition, colony formation, scratch assays, and transwell assays were employed to determine the impact on tumor progression and metastasis. CD276 expression was detected by western blotting following the knockdown of ITGB5. ELISA was utilized to measure serum ITGB5 levels.
RESULTS
The expression of ITGB5 in GC tissue surpassed that in normal tissue, it might contribute to GC pathogenesis through pathways including PI3K-AKT, ECM-receptor interaction, and TGF-beta. The elevated ITGB5 expression is associated with poor prognosis in GC patients. In addition, a strong positive association between ITGB5 overexpression and the infiltration levels of macrophages and monocytes, and it significantly influenced immune response. Moreover, lower expression of ITGB5 was associated with better immunotherapy efficacy. Subsequent investigation demonstrated that silencing of ITGB5 suppressed the proliferation and migration of GC cell lines in vitro. ITGB5 expression was positively correlated with CD276 expression and the knockdown of ITGB5 resulted a notable decrease CD276 expression. Futhermore, a significantly high level of serum ITGB5 was observed in GC patients. The combined assessment of ITGB5, CEA, and CA19-9 improved the diagnostic accuracy.
CONCLUSIONS
ITGB5 potentially serve as both a diagnostic biomarker and therapeutic target in managing GC.
背景
整合素β5（ITGB5）是胃癌（GC）发病机制中的关键因素。我们旨在探讨 ITGB5 作为 GC 诊断和免疫治疗预测因子的潜在价值。
方法
使用癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）评估 ITGB5 在 GC 中的表达，并通过定量聚合酶链反应（qPCR）和免疫组织化学进行验证。采用 Kaplan-Meier 曲线评估预后意义。使用 CIBERSORT、TIMER 和 TISIDB 检测免疫细胞浸润、肿瘤突变负担（TMB）和免疫表型评分（IPS）。此外，采用集落形成、划痕试验和 Transwell 试验来确定其对肿瘤进展和转移的影响。敲低 ITGB5 后，通过 Western blot 检测 CD276 的表达。采用 ELISA 测量血清 ITGB5 水平。
结果
GC 组织中 ITGB5 的表达高于正常组织，其可能通过 PI3K-AKT、ECM-受体相互作用和 TGF-β等途径促进 GC 的发病机制。ITGB5 高表达与 GC 患者的不良预后相关。此外，ITGB5 过表达与巨噬细胞和单核细胞浸润水平呈强烈正相关，显著影响免疫反应。此外，ITGB5 低表达与更好的免疫治疗疗效相关。进一步研究表明，体外沉默 ITGB5 抑制 GC 细胞系的增殖和迁移。ITGB5 表达与 CD276 表达呈正相关，敲低 ITGB5 导致 CD276 表达显著下降。此外，GC 患者血清中 ITGB5 水平明显升高。联合评估 ITGB5、CEA 和 CA19-9 可提高诊断准确性。
结论
ITGB5 可能作为 GC 诊断和治疗的生物标志物和治疗靶点。
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