EGFR expression in patients with stage III colorectal cancer after adjuvant chemotherapy and on cancer cell function

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.

Gefitinib loaded nanostructured lipid carriers: characterization, evaluation and anti-human colon cancer activity in vitro

“…Thus, the rate of incidence and mortality of colorectal cancer have been low compared to earlier days (Siegel et al, 2017). Among the cancer pathways, epidermal growth factor receptor (EGFR) plays a crucial role in the carcinogenesis, invasion and metastasis of colorectal cancer (Huang et al, 2017). Gefitinib (GEF) is a selective inhibitor of EGFR tyrosine kinase and it has been widely used in the treatment of lung cancer, either as monotherapy or in combination with other agents (Chang et al, 2018).…”

“…Gefitinib (GEF) is a selective inhibitor of EGFR tyrosine kinase and it has been widely used in the treatment of lung cancer, either as monotherapy or in combination with other agents (Chang et al, 2018). In colorectal cancer, GEF has been significantly reduced cell proliferation, colony formation and migration in vitro (Huang et al, 2017). Clinical trial conducted with GEF as single or combination therapy showed promising results in colorectal cancers (Gelibter et al, 2007).…”

The Survival Impact of Fluoropyrimidine Metronomic Maintenance Therapy Following Adjuvant Oxaliplatin-based Chemotherapy in Patients with Stage III Colorectal Cancer after Radical Resection: Functional Roles of EGFR as a Potential Predictor

“…Moreover, cell proliferation and migration could be inhibited by fluoropyrimidine-based therapy. In this study, we used Caco-2 cells to perform the in vitro and in vivo experiments because they express EGFR and exhibit no mutations in the oncogenic gene KRAS [20]. We showed that after CRISPR gRNA transfection, the EGFR protein level in the Caco-2 cells decreased substantially.…”

“…Immunoreactivity for EGFR (membrane staining) was categorized according to the presence of tumor cell staining and staining intensity, as mentioned in our previous studies [19,20]. The Caco-2 cells were cultured in DMEM supplemented with 10% FBS and 1% penicillinstreptomycin at 37% and 5% CO2 in humidified atmosphere.…”

“…Our previous study demonstrated that epidermal growth factor receptor (EGFR) expression has a prognostic value specifically in patients with metachronous metastatic CRC (mCRC) [19]. We also demonstrated that tumor EGFR expression is a significant independent negative predictive factor for postoperative relapse and a significant independent negative prognostic factor for DFS and OS in patients with stage III CRC who have undergone radical resection surgery and adjuvant chemotherapy with the FOLFOX regimen [20]. Accordingly, we conducted the present retrospective study to evaluate the survival effects of metronomic maintenance therapy with capecitabine after adjuvant oxaliplatin-based regimen therapy in patients with stage III CRC who had undergone radical resection; the conducted this evaluation according to EGFR expression levels.…”