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Association between clinicopathological features and survival in patients with primary and paired metastatic colorectal cancer and KRAS mutation

Authors Pang X, Li Q, Ma Z, Shi Y, Ma Y, Li X, Cui W, Zhang W

Received 25 January 2017

Accepted for publication 31 March 2017

Published 19 May 2017 Volume 2017:10 Pages 2645—2654

DOI https://doi.org/10.2147/OTT.S133203

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Federico Perche

Peer reviewer comments 2

Editor who approved publication: Dr William Cho

Xue-Lian Pang,* Qiao-Xin Li,* Zhi-Ping Ma, Yi Shi, Yu-Qing Ma, Xin-Xia Li, Wen-Li Cui, Wei Zhang

Department of Pathology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China

*These authors contributed equally to this work

Abstract: The KRAS gene mutation is involved in several types of tumors. However, the potential role of the KRAS mutation in human primary and paired metastatic colorectal cancer (CRC) among different nationalities is poorly understood. In the present study, we assessed the relationship between KRAS mutation status and overall survival (OS) and disease-free survival (DFS) in 230 patients with primary and paired metastatic CRC. The KRAS mutation rate in primary CRC tissue was 43.0% (99/230), which was higher than in paired metastatic CRC, which was 31.9% (23/72; P<0.001). Clinicopathologically, the KRAS gene mutation rate was higher in tumors that had infiltrated more deeply (T3, T4) and in lymph node (LN) metastases (N1/N2) (P=0.029 and P=0.010, respectively). The KRAS gene status did not differ between the Han and Uyghur nationalities in both primary and metastatic CRC. In 72 paired cases, the KRAS mutation rate in primary CRC was significantly higher than in metastatic CRC (P<0.001) and in metastatic CRC that had infiltrated more deeply (T3, T4) (P=0.034). In the metastatic cases, the KRAS gene mutation rate was higher in patients aged over 65 years (P=0.035). Specifically, KRAS mutation was correlated with a poorer OS and DFS (P=0.004 and P=0.029, respectively). In our study, 35 patients with wild-type KRAS who received cetuximab targeted therapy had a better DFS than patients with mutant KRAS (P=0.029). The results of the current study demonstrate that the KRAS status is significantly associated with infiltrating LN metastases and the TNM stage in primary CRC. In addition, the results show that the KRAS mutation is significantly more common in primary tumors than in paired metastatic CRC, and the KRAS mutation is correlated with a shorter OS and DFS, as patients with wild-type KRAS who received cetuximab experienced a longer DFS.

Keywords: CRC, KRAS, primary, metastatic, cetuximab, survival
 

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