Abstract
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 in vitro CRC cell line study through the knockdown of EGFR 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 in vitro cell line study showed that the knockdown of EGFR expression significantly reduced CRC cell proliferation, colony formation and migration. The results of in vitro and in vivo 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.
Highlights
Colorectal cancer (CRC) is the third most common cancer and the third leading cause of cancer death in the United States where an estimated 135,430 newly diagnosed cases of colorectal cancer (CRC) and an estimated 50,260 cancer deaths due to CRC were reported in 2017 [1]
We demonstrated that epidermal growth factor receptor (EGFR) expression has a prognostic value only in patients with metachronous metastatic CRC [12]
Positive EGFR expression was more common in the men than in the women (67.6% vs. 32.4%, p = 0.028)
Summary
Colorectal cancer (CRC) is the third most common cancer and the third leading cause of cancer death in the United States where an estimated 135,430 newly diagnosed cases of CRC and an estimated 50,260 cancer deaths due to CRC were reported in 2017 [1]. In Taiwan, CRC is the most common type of cancer; its prevalence has increased rapidly, and it has been the third leading cause of cancer-related death since 2015. In Taiwan, the 5-year overall survival (OS) for stage I, II, III, and IV CRC were 80.9%, 71.2%, 59.9%, and 12.3%, respectively, in 2013 [2]. Yang et al [3] reported that the 5-year OS rates for stage I and II, III, and IV CRC were 80%–90%, 60%, and 8%, respectively. Patients with locally advanced CRC who underwent adjuvant chemotherapy had a 5-year disease free survival (DFS) of 73.3% [4]. CRC is a heterogenous disease, which means that its clinicopathological features and the conventional tumor-node-metastasis (TNM) staging system can not reflect its real prognosis. The identification of molecular markers that can predict the progress, relapse, and metastasis of CRC is necessary
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