Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan.
Department of Medical Imaging, Chi Mei Medical Center, Tainan, Taiwan.
Oncology. 2020;98(8):549-557. doi: 10.1159/000506991. Epub 2020 May 14.
BACKGROUND/AIM: A great proportion of patients with rectal cancer initially present with locally advanced disease and can potentially benefit from neoadjuvant concurrent chemoradiotherapy (CCRT) for downstaging before surgery. However, risk and clinical outcome stratification remain a great challenge. We aimed to find the potential biomarker to predict the effect of neoadjuvant CCRT on rectal cancer.
We identified epiregulin (EREG) as the most significant predictive marker for neoadjuvant CCRT response from the published rectal cancer transcriptome data set GSE35452. We collected 172 biopsy specimens from rectal cancer patients who received neoadjuvant CCRT followed by radical proctectomy, performed EREG immunohistochemistry, and analyzed the H-scores. We further examined the correlations between the expression level of EREG and clinicopathological features, tumor regression grade, and survival, including disease-specific survival (DSS), locoregional recurrence-free survival (LRFS), and metastasis-free survival (MeFS).
High EREG expression was significantly related to early pretreatment (pre-Tx) and posttreatment (post-Tx) tumor status (T1, T2, p = 0.047 and p < 0.001), pre-Tx and post-Tx negative nodal status (N0, p < 0.001 and p = 0.004), less vascular and perineurial invasion (p = 0.015 and p = 0.023), and higher tumor regression grade (p < 0.001). In the survival analysis, high EREG expression was significantly associated with better DSS (p < 0.0001), LRFS (p = 0.0004), and MeFS (p < 0.0001). In the multivariate analysis, high EREG expression remained prognostically significant for better DSS (p = 0.003; hazard ratio: 5.599).
These data suggest that EREG is a potential predictive marker and therapeutic target in rectal cancer patients receiving neoadjuvant CCRT.
背景/目的：相当一部分直肠癌患者最初表现为局部晚期疾病，在手术前进行新辅助同期放化疗（CCRT）降期可能会受益。然而，风险和临床结果分层仍然是一个巨大的挑战。我们旨在寻找预测新辅助 CCRT 对直肠癌疗效的潜在生物标志物。
我们从已发表的直肠癌转录组数据集 GSE35452 中确定表皮调节素（EREG）为新辅助 CCRT 反应的最显著预测标志物。我们收集了 172 例接受新辅助 CCRT 后行根治性直肠切除术的直肠癌患者的活检标本，进行 EREG 免疫组织化学染色，并分析 H 评分。我们进一步研究了 EREG 表达水平与临床病理特征、肿瘤退缩分级以及生存（包括疾病特异性生存（DSS）、局部无复发生存（LRFS）和无转移生存（MeFS））之间的相关性。
高 EREG 表达与早期预处理（pre-Tx）和后处理（post-Tx）肿瘤状态（T1、T2，p = 0.047 和 p < 0.001）、pre-Tx 和 post-Tx 阴性淋巴结状态（N0，p < 0.001 和 p = 0.004）、较少的血管和神经周围侵犯（p = 0.015 和 p = 0.023）以及更高的肿瘤退缩分级（p < 0.001）显著相关。在生存分析中，高 EREG 表达与更好的 DSS（p < 0.0001）、LRFS（p = 0.0004）和 MeFS（p < 0.0001）显著相关。在多变量分析中，高 EREG 表达仍然是 DSS 预后良好的显著因素（p = 0.003；风险比：5.599）。
这些数据表明，EREG 是接受新辅助 CCRT 的直肠癌患者的潜在预测标志物和治疗靶点。
