and mutations predict overall survival of stage II/III colorectal cancer patients.

AIM

To investigate the predictive value of and mutation status in colorectal cancer (CRC) patients treated with 5-fluorouracil-based chemotherapy.

METHODS

In this study, a total of 315 patients with histologically proven CRC were enrolled from Yangpu Hospital affiliated to Shanghai Tongji University between 2007 and 2011. Of these patients, 241 with stage II/III CRC received 5-fluorouracil-based adjuvant chemotherapy. Formalin-fixed paraffin-embedded lesion samples of the patients with curatively resected CRC were collected. Next-generation sequencing was performed to identify somatic gene mutations. The correlation of and mutation status with overall survival (OS) was analyzed using a Cox proportional hazard model and the Kaplan-Meier method.

RESULTS

Among the 241 patients with stage II/III in this cohort, the and/or mutation was detected in 177 patients, among which 54 patients had and double mutations. The or mutation was not significantly correlated with OS in univariate and multivariate analyses. Compared with patients without and mutations, those with double mutations showed a significantly worse survival (univariate HR = 2.21; 95%CI: 1.15-4.24; multivariate HR = 2.02; 95%CI: 1.04-3.91). The mutation located in the kinase domain showed a trend toward a shorter OS compared with wild-type tumors (multivariate HR = 1.56; 95%CI: 1.00-2.44; = 0.052). The Kaplan-Meier curve showed that patients harboring the mutation located in the kinase domain had a worse clinical outcome than those with wild-type status (Log-rank = 0.041).

CONCLUSION

Double mutation of and is correlated with a shorter OS in stage II/III CRC patients treated with 5-fluorouracil-based therapy.