Objective To investigate the effects of KRAS mutation isoforms on tumor regression grade (TRG) of rectal cancer received neoadjuvant therapy.

Methods The clinicopathologic data of patients with locally advanced and metastatic rectal cancer (stage Ⅲ-Ⅳ) who underwent radical tumor resection after neoadjuvant therapy were collected. The correlations between the mutated subtypes of KRAS and TRG as well as the clinicopathological features were analyzed.

Results A total of 95 patients were enrolled, including 55 patients with poor tumor regression. The incidences of G12V mutation in exon 2 and A146 mutation in exon 4 of the KRAS gene were higher in the group with poor tumor regression than those in the significant tumor regression group (P < 0.05). In patients with G12D mutation of KRAS gene, the histological grade of tumor in poor tumor regression was higher than that in significant tumor regression group (P＝0.027). In patients with poor tumor regression, the levels of CD8⁺, PD-1⁺ T-lymphocyte infiltration were higher in G12D mutation subgroup than those in G12V mutation and G13D mutation subgroups (P < 0.05).

Conclusions KRAS G12V mutation and A146 mutation suggest poor neoadjuvant therapy effect for rectal cancer; for patients with KRAS G12D mutation and poor tumor regression, the potential beneficiary for immunotherapy would be screened by detecting CD8⁺ and PD-1⁺ T-lymphocyte infiltration.