Impact of KRAS,NRAS,and BRAF gene mutations on the efficacy of neoadjuvant therapy and postoperative hepatic metastasis occurrence in patients with stage Ⅱ-Ⅲ mid-low rectal cancer
10.3969/j.issn.1009-9905.2025.06.005
- VernacularTitle:KRAS、NRAS、BRAF基因突变对Ⅱ~Ⅲ期中低位直肠癌患者新辅助治疗疗效及术后肝转移的影响
- Author:
Li-dan LUO
1
;
Ping-ping LIU
1
;
Xian-yin CHEN
1
;
Da-chao CHEN
1
Author Information
1. 第九〇九医院(厦门大学附属东南医院)肿瘤科(福建 漳州 363000)
- Publication Type:Journal Article
- Keywords:
Rectal neoplasms;
Gene mutation;
Neoadjuvant therapy;
Liver metastasis
- From:
Chinese Journal of Current Advances in General Surgery
2025;28(6):451-456
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect of KRAS,NRAS and BRAF gene mutations on the efficacy of pre-operative short-course radiotherapy combined with chemotherapy and postoperative liver metastasis in patients with stage Ⅱ~Ⅲ mid-low rectal cancer.Methods:The clinical data of 149 patients with stage Ⅱ~Ⅲ low rectal cancer admitted to Dongnan Hospital of Xiamen University from January 2017 to June 2020 were retrospectively analyzed.All patients received neoadjuvant therapy with preoperative short-course radiotherapy combined with chemotherapy and radical surgery,and were followed up until June 30,2023.The mutations of KRAS,NRAS and BRAF genes were de-tected by pathological tissue before surgery.The effect of neoadjuvant therapy was evaluated according to tumor re-gression grade(TRG).The risk factors of postoperative liver metastasis were analyzed by Logistic multivariate analysis.Results:There were 44 cases of KRAS,10 cases of NRAS and 12 cases of BRAF gene mutation in 149 patients with stage Ⅱ~Ⅲ low rectal cancer,and the mutation rates were 29.53%,6.71%and 8.05%.The incidence of positive vas-cular invasion in patients with KRAS gene mutation was higher than negative(P<0.05).In NRAS mutation patients,the incidence of positive lymph node metastasis was higher than negative(P<0.05),and the incidence of maximum tumor diameter≥5 cm was higher than that of maximum tumor diameter<5 cm(P<0.05).The clinical stage of BRAF muta-tion was higher in stage Ⅲ than in stage Ⅱ(P<0.05),and the incidence of positive lymph node metastasis was higher than negative(P<0.05).During the follow-up period,liver metastasis occurred in 42 patients,and the liver metastasis rate was 28.18%.The KRAS,NRAS and BRAF gene mutations in the effective group were 25.81%,2.15%and 3.23%,lower than those in the ineffective group(35.71%,14.29%and 17.07%,P<0.05).Multiple factors found clinical stage Ⅲ(OR=10.620,95%CI:2.645~22.575),lymph node metastasis was positive(OR=8.774,95%CI:1.878~19.645),neoadju-vant therapy failed(OR=3.373,95%CI:1.014~11.218),KRAS gene mutation(OR=6.245,95%CI:1.876~20.789),BRAF gene mutation(OR=9.497,95%CI:1.754~19.335)were independent risk factors for postoperative liver metastasis of stage Ⅱ~Ⅲ mid-low rectal cancer.Conclusion:Mutations in the KRAS and BRAF genes of middle are associated with poorer efficacy of neoadjuvant therapy in patients with stage Ⅱ~Ⅲ mid-low rectal cancer and are also indepen-dent risk factors for postoperative liver metastasis.