Department of Nephrology, The First Affiliated Hospital of Nanchang University, Jiangxi, China; Urological Cancer Center for Research and Innovation (UCCRI), St Joseph's Hospital, Hamilton, ON L8N 4A6, Canada; Department of Surgery, McMaster University, Hamilton, ON L8S 4K1, Canada; The Research Institute of St Joe's Hamilton, St Joseph's Hospital, Hamilton, ON L8N 4A6, Canada.
Urological Cancer Center for Research and Innovation (UCCRI), St Joseph's Hospital, Hamilton, ON L8N 4A6, Canada; Department of Surgery, McMaster University, Hamilton, ON L8S 4K1, Canada; The Research Institute of St Joe's Hamilton, St Joseph's Hospital, Hamilton, ON L8N 4A6, Canada.
J Adv Res. 2023 Dec;54:195-210. doi: 10.1016/j.jare.2023.01.015. Epub 2023 Jan 18.
IQGAP3 possesses oncogenic actions; its impact on prostate cancer (PC) remains unclear.
We will investigate IQGAP3's association with PC progression, key mechanisms, prognosis, and immune evasion.
IQGAP3 expression in PC was examined by immunohistochemistry and using multiple datasets. IQGAP3 network was analyzed for pathway alterations and used to construct a multigene signature (SigIQGAP3NW). SigIQGAP3NW was characterized using LNCaP cell-derived castration-resistant PCs (CRPCs), analyzed for prognostic value in 26 human cancer types, and studied for association with immune evasion.
Increases in IQGAP3 expression associated with PC tumorigenesis, tumor grade, metastasis, and p53 mutation. IQGAP3 correlative genes were dominantly involved in mitosis. IQGAP3 correlated with PLK1 and TOP2A expression at Spearman correlation/R = 0.89 (p ≤ 3.069e-169). Both correlations were enriched in advanced PCs and Taxane-treated CRPCs and occurred at high levels (R > 0.8) in multiple cancer types. SigIQGAP3NW effectively predicted cancer recurrence and poor prognosis in independent PC cohorts and across 26 cancer types. SigIQGAP3NW stratified PC recurrence after adjustment for age at diagnosis, grade, stage, and surgical margin. SigIQGAP3NW component genes were upregulated in PC, metastasis, LNCaP cell-produced CRPC, and showed an association with p53 mutation. SigIQGAP3NW correlated with immune cell infiltration, including Treg in PC and other cancers. RELT, a SigIQGAP3NW component gene, was associated with elevations of multiple immune checkpoints and the infiltration of Treg and myeloid-derived suppressor cells in PC and across cancer types. RELT and SigIQGAP3NW predict response to immune checkpoint blockade (ICB) therapy.
In multiple cancers, IQGAP3 robustly correlates with PLK1 and TOP2A expression, and SigIQGAP3NW and/or RELT effectively predict mortality risk and/or resistance to ICB therapy. PLK1 and TOP2A inhibitors should be investigated for treating cancers with elevated IQGAP3 expression. SigIQGAP3NW and/or RELT can be developed for clinical applications in risk stratification and management of ICB therapy.
IQGAP3 具有致癌作用；其对前列腺癌（PC）的影响尚不清楚。
我们将研究 IQGAP3 与 PC 进展、关键机制、预后和免疫逃逸的关系。
通过免疫组织化学和使用多个数据集检查 IQGAP3 在 PC 中的表达。分析 IQGAP3 网络的通路改变，并用于构建多基因特征（SigIQGAP3NW）。使用来源于 LNCaP 细胞的去势抵抗性前列腺癌（CRPC）来描述 SigIQGAP3NW 的特征，分析其在 26 种人类癌症类型中的预后价值，并研究其与免疫逃逸的关系。
IQGAP3 表达的增加与 PC 的发生、肿瘤分级、转移和 p53 突变有关。IQGAP3 相关基因主要参与有丝分裂。IQGAP3 与 Spearman 相关分析中的 PLK1 和 TOP2A 表达呈正相关/R=0.89（p≤3.069e-169）。这两种相关性在晚期 PC 和紫杉醇治疗的 CRPC 中均丰富，并且在多种癌症类型中均呈高水平（R>0.8）。SigIQGAP3NW 在独立的 PC 队列和 26 种癌症类型中均能有效预测癌症复发和不良预后。SigIQGAP3NW 在调整诊断时的年龄、分级、分期和手术切缘后，对 PC 复发进行分层。SigIQGAP3NW 组成基因在 PC、转移、LNCaP 细胞产生的 CRPC 中上调，并与 p53 突变相关。SigIQGAP3NW 与包括 PC 中的 Treg 和其他癌症中的 Treg 和髓源抑制细胞在内的免疫细胞浸润相关。SigIQGAP3NW 的组成基因 RELT 与多个免疫检查点的升高以及 Treg 和髓源抑制细胞在 PC 和癌症类型中的浸润相关。RELT 和 SigIQGAP3NW 预测对免疫检查点阻断（ICB）治疗的反应。
在多种癌症中，IQGAP3 与 PLK1 和 TOP2A 表达密切相关，SigIQGAP3NW 和/或 RELT 可有效预测死亡率风险和/或对 ICB 治疗的耐药性。应研究 PLK1 和 TOP2A 抑制剂治疗 IQGAP3 表达升高的癌症。SigIQGAP3NW 和/或 RELT 可用于临床风险分层和 ICB 治疗管理。
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