Huang Ching-Wen, Chen Yi-Ting, Tsai Hsiang-Lin, Yeh Yung-Sung, Su Wei-Chih, Ma Cheng-Jen, Tsai Tsen-Ni, Wang Jaw-Yuan
Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Oncotarget. 2017 Dec 9;8(70):114663-114676. doi: 10.18632/oncotarget.23072. eCollection 2017 Dec 29.
The epidermal growth factor receptor (EGFR)/RAS/RAF/MEK/MAPK pathway plays a crucial role in the carcinogenesis, invasion and metastasis of colorectal cancer (CRC). However, its role in the prognosis and prediction of relapse in patients with stage III CRC after adjuvant chemotherapy remains controversial. In the present study, the clinicopathological features of 173 patients with stage III CRC who underwent radical resection and adjuvant chemotherapy with the fluoropyrimidine/folinic acid, and oxaliplatin (FOLFOX) regimen, and their prognostic values of EGFR expression were retrospectively analyzed. By conducting an CRC cell line study through the knockdown of expression, we analyzed cell proliferation, colony formation and migration. Positive EGFR expression and an abnormal postoperative serum carcinoembryonic antigen (CEA) level were found to be significant independent negative predictive factors for postoperative relapse. Furthermore, positive EGFR expression was a significant independent negative prognostic factor for disease-free survival (DFS) and overall survival (OS). Additionally, an cell line study showed that the knockdown of EGFR expression significantly reduced CRC cell proliferation, colony formation and migration. The results of and experiments demonstrated that EGFR expression had a prognostic value for OS and DFS, as well as predictive roles for postoperative relapse, in patients with stage III CRC. By analyzing both EGFR expression and the postoperative CEA, the patients with stage III CRC who were at a high risk of postoperative relapse, or mortality following adjuvant chemotherapy could be identified. In short, CRC cells with EGFR expression would exhibit a highly malignant behavior.
表皮生长因子受体(EGFR)/RAS/RAF/MEK/MAPK信号通路在结直肠癌(CRC)的发生、侵袭和转移中起关键作用。然而,其在III期CRC患者辅助化疗后复发的预后和预测中的作用仍存在争议。在本研究中,回顾性分析了173例接受根治性切除并采用氟嘧啶/亚叶酸和奥沙利铂(FOLFOX)方案进行辅助化疗的III期CRC患者的临床病理特征及其EGFR表达的预后价值。通过对EGFR表达进行敲低的CRC细胞系研究,分析细胞增殖、集落形成和迁移情况。发现EGFR阳性表达和术后血清癌胚抗原(CEA)水平异常是术后复发的显著独立负性预测因素。此外,EGFR阳性表达是无病生存期(DFS)和总生存期(OS)的显著独立负性预后因素。另外,细胞系研究表明,敲低EGFR表达可显著降低CRC细胞增殖、集落形成和迁移。体内和体外实验结果表明,EGFR表达对III期CRC患者的OS和DFS具有预后价值,对术后复发也具有预测作用。通过分析EGFR表达和术后CEA,可识别出III期CRC患者中术后复发或辅助化疗后死亡风险较高的患者。简而言之,具有EGFR表达的CRC细胞将表现出高度恶性行为。