Department of Laboratory Medicine and Pathology, University of Alberta, 8440 112 Street NW, Edmonton, AB, T6G 2B7, Canada.
Department of Laboratory Medicine and Pathology, University of Alberta and Cross Cancer Institute, 11560 University Avenue, Edmonton, AB, T6G 1Z2, Canada.
J Cancer Res Clin Oncol. 2022 Jun;148(6):1325-1336. doi: 10.1007/s00432-022-03924-3. Epub 2022 Jan 28.
The risk assessment classification schemes for gastrointestinal stromal tumors (GIST) include tumor site, size, mitotic count and variably tumor rupture. Heterogeneity in high-risk GIST poses limitations for current classification schemes. This study aims to demonstrate the clinical utility of risk stratification by gene expression profiling (GEP) using Nanostring technology.
Fifty-six GIST cases were analyzed using a 231 gene expression panel. GEP results were correlated with clinical and pathological data. The prognostic performance was assessed in 34 patients with available survival data using ROC curves, Kaplan-Meier survival curves and compared with traditional risk assessment schemes. Volcano plot analysis identified seven genes with significantly higher expression (FDR < .0.05) in high-risk than in non-high-risk tumors, namely TYMS, CDC2, TOP2A, CCNA2, E2F1, PCNA, and BIRC5. Together, these transcripts exhibited significantly higher expression in high-risk tumors than in intermediate (P < 0.01), low (P < 0.001), and very low (P = 0.01) risk tumors. Receiver-operating characteristic curve analysis demonstrated area under the curve (AUC) to be 0.858 for the separation of high-risk and non-high-risk tumors. Kaplan-Meier survival analysis demonstrated improved risk stratification (log-rank test P < 0.001) compared to the current risk assessment classification (P = 0.231).
In addition to current clinical and histology-based risk classification for patients with GIST, gene expression may offer complementary prognostic information.
胃肠道间质瘤（GIST）的风险评估分类方案包括肿瘤部位、大小、有丝分裂计数和肿瘤破裂的可变性。高危 GIST 的异质性对当前的分类方案提出了限制。本研究旨在展示使用 Nanostring 技术进行基因表达谱（GEP）风险分层的临床实用性。
使用 231 个基因表达谱分析了 56 例 GIST 病例。GEP 结果与临床和病理数据相关联。在 34 例具有可用生存数据的患者中，使用 ROC 曲线、Kaplan-Meier 生存曲线评估预后性能，并与传统风险评估方案进行比较。火山图分析鉴定出在高危肿瘤中表达显著更高（FDR < 0.05）的七个基因，即 TYMS、CDC2、TOP2A、CCNA2、E2F1、PCNA 和 BIRC5。这些转录物一起在高危肿瘤中的表达明显高于中危（P < 0.01）、低危（P < 0.001）和极低危（P = 0.01）肿瘤。接收者操作特征曲线分析表明，高危和非高危肿瘤之间的曲线下面积（AUC）为 0.858。Kaplan-Meier 生存分析表明，与当前风险评估分类（P = 0.231）相比，风险分层得到了改善（对数秩检验 P < 0.001）。
除了患者 GIST 的当前临床和基于组织学的风险分类外，基因表达可能提供补充的预后信息。
