Background:There is an urgent clinical need to select the patients with resectable gastrointestinal stromal tumors (GISTs) who can benefit from adjuvant treatment after complete resection based on disease recurrence risk stratification. We hypothesized that integrating biomarkers into available risk assessment tools may improve the precision of GIST prognostic predictions. Methods:Candidate genes that may cause GIST progression were identified using the Gene Expression Omnibus dataset GSE20708. Quantitative Real-time was used to confirm the prognostic value of the candidate genes for recurrence-free survival (RFS) in a cohort of 94 patients. Results: Thirty-seven differentially expressed genes between localized tumors and metastatic primary tumors were found; 14 (37.8%) were upregulated and 23 (62.2%) were downregulated in the latter tumors. Low-density lipoprotein receptor class A domain containing 4 (LDLRAD4) was selected for further prognostic analysis. Although LDLRAD4 mRNA expression was not associated with recurrence risk grades as determined by the revised NIH consensus criteria, multivariate Cox regression analysis showed that LDLRAD4 expression (hazard ratio [HR] = 4.403, 95% confidence interval [CI]: 1.822-10.641, P = 0.001), tumor size (HR = 1.174, 95% CI: 1.027-1.342, P = 0.019) and tumor location (HR = 6.291, 95% CI: 1.128-35.080, P = 0.036) were independent prognostic factors for RFS in patients with resectable GISTs. Moreover, the RFS model constructed by these three factors may effectively predict GIST prognosis within the first 2 postsurgical years. Conclusion: Our study identifies LDLRAD4 as a suitable prognostic marker for GISTs. The integration of biomarkers into risk assessment tools may improve the precision of GIST prognostic predictions.

背景：临床迫切需要根据疾病复发风险分层选择可切除的胃肠道间质瘤（GISTs）患者，这些患者在完全切除后可从辅助治疗中获益。我们假设将生物标志物整合到可用的风险评估工具中可能会提高 GIST 预后预测的准确性。方法：使用基因表达综合数据集 GSE20708 鉴定可能导致 GIST 进展的候选基因。在 94 名患者的队列中，使用实时定量来确认无复发生存 (RFS) 候选基因的预后价值。结果：发现局部肿瘤与转移性原发肿瘤37个差异表达基因；在后一种肿瘤中，14 个（37.8%）上调，23 个（62.2%）下调。选择低密度脂蛋白受体 A 类结构域包含 4 (LDLRAD4) 进行进一步的预后分析。尽管 LDLRAD4 mRNA 表达与修订后的 NIH 共识标准确定的复发风险等级无关，但多变量 Cox 回归分析显示 LDLRAD4 表达（风险比 [HR] = 4.403，95% 置信区间 [CI]：1.822-10.641，P  = 0.001)、肿瘤大小（HR = 1.174，95% CI：1.027-1.342，P  = 0.019）和肿瘤位置（HR = 6.291，95% CI：1.128-35.080，P = 0.036) 是可切除 GIST 患者 RFS 的独立预后因素。此外，由这三个因素构建的RFS模型可以有效预测术后前2年内GIST的预后。结论：我们的研究将 LDLRAD4 确定为 GIST 的合适预后标志物。将生物标志物整合到风险评估工具中可能会提高 GIST 预后预测的准确性。