Oncotarget

Research Papers:

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

Ching-Wen Huang, Yi-Ting Chen, Hsiang-Lin Tsai, Yung-Sung Yeh, Wei-Chih Su, Cheng-Jen Ma, Tsen-Ni Tsai and Jaw-Yuan Wang _

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Oncotarget. 2017; 8:114663-114676. https://doi.org/10.18632/oncotarget.23072

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Abstract

Ching-Wen Huang1,2,3, Yi-Ting Chen3,4,5, Hsiang-Lin Tsai1,2, Yung-Sung Yeh1,6,7, Wei-Chih Su1,2,6, Cheng-Jen Ma1,8, Tsen-Ni Tsai1 and Jaw-Yuan Wang1,2,6,9,10,11

1Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

2Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

3Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

4Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

5Department of Pathology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

6Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

7Division of Trauma and Surgical Critical Care, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

8Division of General and Digestive Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

9Center for Biomarkers and Biotech Drugs, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

10Research Center for Environmental Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

11Research Center for Natural Products and Drug Development, Kaohsiung Medical University, Kaohsiung, Taiwan

Correspondence to:

Jaw-Yuan Wang, email: cy614112@ms14.hinet.net, jawyuanwang@gmail.com

Keywords: epidermal growth factor receptor; prognostic value; stage III colorectal cancer; postoperative carcinoembryonic antigen

Received: August 14, 2017     Accepted: November 14, 2017     Published: December 09, 2017

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.


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