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