Abstract

For patients with metastatic colorectal cancer (mCRC), epidermal growth factor receptor (EGFR) inhibitors are limited to patients with RAS wild-type tumours. Not all patients will benefit from treatment and better predictive biomarkers are needed. Here we investigated the prognostic and predictive impact of the EGFR ligands amphiregulin (AREG) and epiregulin (EREG). Expression levels were assessed by immunohistochemistry on 99 KRAS wild-type tumours. AREG and EREG positivity was seen in 49% and 50% of cases, respectively. No difference in expression was observed by primary tumour side. There was no significant difference in OS by AREG or EREG expression. In the subset of patients who received an EGFR inhibitor, EREG positivity was associated with longer OS (median 34.0 vs. 27.0 months, p = 0.033), driven by a difference in patients with a left-sided primary (HR 0.37, p = 0.015). Our study supports further investigation into EREG as a predictive biomarker in mCRC.

摘要

对于转移性结直肠癌 (mCRC) 患者，表皮生长因子受体 (EGFR) 抑制剂仅限于RAS野生型肿瘤患者。并非所有患者都会从治疗中受益，因此需要更好的预测性生物标志物。在这里，我们研究了 EGFR 配体双调蛋白 (AREG) 和上皮调节蛋白 (EREG) 的预后和预测影响。通过免疫组织化学对 99 KRAS评估表达水平野生型肿瘤。AREG 和 EREG 阳性分别见于 49% 和 50% 的病例。原发肿瘤侧未观察到表达差异。AREG 或 EREG 表达对 OS 没有显着差异。在接受 EGFR 抑制剂的患者亚组中，EREG 阳性与更长的 OS 相关（中位 34.0 个月对 27.0 个月，p  = 0.033），这是由左侧原发性患者的差异驱动的（HR 0.37，p  = 0.015 ）。我们的研究支持进一步研究 EREG 作为 mCRC 的预测性生物标志物。