Abstract:

Objective To investigate the role of circulating tumor DNA （ctDNA） V-Ki-ras2 Kirsten ratsarcoma viral oncogene homolog （KRAS） mutation determination for therapeutic effectiveness assessment of neo-adjuvant therapy in locally advanced colorectal cancer patients （cT3N1-2M0 or cT4N0-2M0）. Methods Totally,53 patients with KRAS-mutated locally advanced colorectal cancer who received neo-adjuvant therapy were enrolled. The ctDNA KRAS mutation mutant-allele frequencies （MAF） before and after neo-adjuvant therapy were determined by droplet digital polymerase chain reaction （ddPCR）. The results of computed tomography （CT） of the chest,abdomen and pelvis were collected,and serum carcinoembryonic antigen （CEA） and carbohydrate antigen 19-9 （CA19-9） were determined. Results The MAF values of ctDNA KRAS mutation before neo-adjuvant therapy had statistical significance compared with that after neo-adjuvant therapy in the 53 locally advanced colorectal cancer patients （P<0.05）. With MAF difference （MAF before treatment–MAF after treatment） as dependent variable,the comparative analysis using least-significant difference （LSD） demonstrated that MAF differences were statistically significant between-in the grading groups classified by therapeutic effectiveness assessment with both radiography and pathology （P<0.05）. The changes of serum CEA and CA19-9 （levels before treatment–levels after treatment） were also statistically significant between-in the grading groups of radiographic and pathological therapeutic effectiveness assessment（P<0.05）. Conclusions Peripheral blood ctDNA KRAS mutation allele frequency can be used as a new molecular marker to evaluate the therapeutic effectiveness of neo-adjuvant therapy,which supplements the traditional therapeutic effectiveness assessment of locally advanced colorectal cancer.

Key words: Circulating tumor DNA, V-Ki-ras2 Kirsten ratsarcoma viral oncogene homolog, Neo-adjuvant therapy, Colorectal cancer