We conducted a proteomic analysis using mass spectrometry to identify and validate protein biomarkers for accurately predicting recurrence risk in gastrointestinal stromal tumors (GIST) patients, focusing on differentially expressed proteins in metastatic versus primary GIST tissues. We selected five biomarkers—GPX4, RBM4, TPM3, PFKFB2, and PGAM5—and validated their expressions in primary tumors of recurrent and non-recurrent GIST patients via immunohistochemistry. Our analysis of the association between these biomarkers with recurrence-free survival (RFS) and overall survival (OS), along with their interrelationships, revealed that immunohistochemistry confirmed significantly higher expressions of these biomarkers in primary GIST tissues of recurrent patients. Kaplan-Meier survival analysis showed that high expressions of GPX4, RBM4, TPM3, PFKFB2, and PGAM5 correlated with lower RFS, and GPX4 and RBM4 with lower OS. All biomarker pairs showed positive associations, with high expressions correlating with increased recurrence rates, and GPX4 and RBM4 with higher mortality rates. In conclusion, the biomarkers GPX4, RBM4, TPM3, PFKFB2, and PGAM5 are clinically relevant for predicting GIST recurrence, with their high expressions in primary tumors linked to poorer RFS and OS. They serve as potential prognostic indicators, enabling early treatment and improved outcomes. The observed interrelationships among these biomarkers further validate their accuracy in predicting GIST recurrence.

中文翻译：

---

预测胃肠道间质瘤复发的蛋白质生物标志物的鉴定和验证

我们使用质谱法进行了蛋白质组学分析，以识别和验证蛋白质生物标志物，以准确预测胃肠道间质瘤 (GIST) 患者的复发风险，重点关注转移性与原发性 GIST 组织中差异表达的蛋白质。我们选择了五种生物标志物——GPX4、RBM4、TPM3、PFKFB2和PGAM5——并通过免疫组织化学验证了它们在复发性和非复发性GIST患者的原发性肿瘤中的表达。我们对这些生物标志物与无复发生存期 (RFS) 和总生存期 (OS) 之间的关联及其相互关系的分析表明，免疫组织化学证实这些生物标志物在复发患者的原发性 GIST 组织中表达显着较高。Kaplan-Meier 生存分析显示，GPX4、RBM4、TPM3、PFKFB2 和 PGAM5 的高表达与较低的 RFS 相关，而 GPX4 和 RBM4 与较低的 OS 相关。所有生物标志物对均显示出正相关性，高表达与复发率增加相关，GPX4 和 RBM4 与更高的死亡率相关。总之，生物标志物 GPX4、RBM4、TPM3、PFKFB2 和 PGAM5 在临床上与预测 GIST 复发相关，它们在原发肿瘤中的高表达与较差的 RFS 和 OS 相关。它们作为潜在的预后指标，有助于早期治疗和改善结果。观察到的这些生物标志物之间的相互关系进一步验证了它们预测 GIST 复发的准确性。