KRAS and metastatic colorectal cancer: There were several experimental evidence which supported our findings, such as ubiquitin ligase TRIM65 promoted CRC metastasis by targeting ARHGAP35 for protein degradation (the Regulation of protein ubiquitination) [31], the NTRK2 (TRKB) signaling pathway has been proven as the treatment target for CRC [32], and EGFR on the receptor tyrosine kinase binding pathway associated with patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer [33].