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

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; cetuximab; metastatic; primary; survival.

Figure 1

(A) Internal control gene in HEX channel. (B) KRAS gene Wild-type in FAM channel. (C) KRAS gene mutant-type in FAM channel. (D) KRAS gene double mutant-type in FAM channel.

Figure 2

KRAS gene single mutation rate of codons 12 and 13 in primary and metastatic CRC. Abbreviation: CRC, colorectal cancer.

Figure 3

The Kaplan-Meier survival curve for patients with the KRAS gene. Notes: (A) Overall survival stratified by KRAS Mut and WT. (B) Disease-free survival stratified by KRAS Mut and WT. (C) Overall survival stratified by KRAS status and chemotherapy. (D) Disease-free survival stratified by KRAS status and chemotherapy. (E) Overall survival stratified by KRAS WT and cetuximab. (F) Disease-free survival stratified by KRAS WT and cetuximab. Abbreviations: che, chemotherapy; cet, cetuximab; Mut, mutation; WT, wild-type.