Department of Pathology, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan.
Department of Surgery, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan.
Pathol Int. 2021 Nov;71(11):752-764. doi: 10.1111/pin.13160. Epub 2021 Sep 15.
It is unclear which prognostic factor such as pathological features and gene mutation are majorly relevant for stage III disease and whether they aid in determining patients who will be benefit from postoperative adjuvant chemotherapy. The expression of astrocyte-elevated gene-1 (AEG-1), thymidylate synthase (TS), excision repair cross-complementation group 1 (ERCC1), epidermal growth factor receptor (EGFR), and vascular endothelial growth factor (VEGF) was examined to investigate their role in adjuvant chemotherapy for patients with resectable stage III colorectal cancer (CRC). A significant positive correlation was observed between AEG-1, TS, ERCC1, EGFR, and VEGF gene expression levels in CRC cell lines, and low AEG-1 and TS expression were highly sensitive to 5-fluorouracil treatment. Our results showed that AEG-1 expression was high in T4 and caused CRC recurrence or metastasis. Patients with T4, high AEG-1, TS and VEGF expression had a significantly short disease-free survival and overall survival. In multivariate Cox regression analysis, high AEG-1 expression could be an independent prognostic factor indicating poor survival in patients with resectable stage III CRC treated with adjuvant chemotherapy. In conclusion, AEG-1 expression and tumor grade are potential prognostic factors for recurrence and survival in patients with stage III CRC receiving adjuvant fluoropyrimidine-based chemotherapy.
尚不清楚哪些预后因素,如病理特征和基因突变,与 III 期疾病关系更密切,以及它们是否有助于确定将从术后辅助化疗中获益的患者。检测了星形细胞上调基因-1(AEG-1)、胸苷酸合成酶(TS)、切除修复交叉互补组 1(ERCC1)、表皮生长因子受体(EGFR)和血管内皮生长因子(VEGF)的表达,以研究它们在可切除的 III 期结直肠癌(CRC)患者辅助化疗中的作用。在 CRC 细胞系中观察到 AEG-1、TS、ERCC1、EGFR 和 VEGF 基因表达水平之间存在显著的正相关,并且低 AEG-1 和 TS 表达对 5-氟尿嘧啶治疗高度敏感。我们的结果表明,AEG-1 在 T4 中高表达导致 CRC 复发或转移。T4、高 AEG-1、TS 和 VEGF 表达的患者无病生存和总生存时间明显缩短。多变量 Cox 回归分析表明,高 AEG-1 表达可作为独立的预后因素,表明接受辅助氟嘧啶类化疗的可切除 III 期 CRC 患者生存不良。总之,AEG-1 表达和肿瘤分级是接受辅助氟嘧啶类化疗的 III 期 CRC 患者复发和生存的潜在预后因素。