Prognostic value of KRAS mutation status in colorectal cancer patients: a population-based competing risk analysis

Dongjun Dai; Yanmei Wang; Liyuan Zhu; Hongchuan Jin; Xian Wang

doi:10.7717/peerj.9149

Prognostic value of KRAS mutation status in colorectal cancer patients: a population-based competing risk analysis

PeerJ. 2020 Jun 1:8:e9149. doi: 10.7717/peerj.9149. eCollection 2020.

Authors

Dongjun Dai¹, Yanmei Wang¹, Liyuan Zhu², Hongchuan Jin², Xian Wang¹

Affiliations

¹ Department of Medical Oncology, Sir Run Run Shaw Hospital, Medical School of Zhejiang University, Zhejiang University, Hangzhou, Zhejiang, China.
² Laboratory of Cancer Biology, Key Lab of Biotherapy, Sir Run Run Shaw Hospital, Medical School of Zhejiang University, Zhejiang University, Hangzhou, Zhejiang, China.

Abstract

Background: To use competing analyses to estimate the prognostic value of KRAS mutation status in colorectal cancer (CRC) patients and to build nomogram for CRC patients who had KRAS testing.

Method: The cohort was selected from the Surveillance, Epidemiology, and End Results database. Cumulative incidence function model and multivariate Fine-Gray regression for proportional hazards modeling of the subdistribution hazard (SH) model were used to estimate the prognosis. An SH model based nomogram was built after a variable selection process. The validation of the nomogram was conducted by discrimination and calibration with 1,000 bootstraps.

Results: We included 8,983 CRC patients who had KRAS testing. SH model found that KRAS mutant patients had worse CSS than KRAS wild type patients in overall cohort (HR = 1.10 (95% CI [1.04-1.17]), p < 0.05), and in subgroups that comprised stage III CRC (HR = 1.28 (95% CI [1.09-1.49]), p < 0.05) and stage IV CRC (HR = 1.14 (95% CI [1.06-1.23]), p < 0.05), left side colon cancer (HR = 1.28 (95% CI [1.15-1.42]), p < 0.05) and rectal cancer (HR = 1.23 (95% CI [1.07-1.43]), p < 0.05). We built the SH model based nomogram, which showed good accuracy by internal validation of discrimination and calibration. Calibration curves represented good agreement between the nomogram predicted CRC caused death and actual observed CRC caused death. The time dependent area under the curve of receiver operating characteristic curves (AUC) was over 0.75 for the nomogram.

Conclusion: This is the first population based competing risk study on the association between KRAS mutation status and the CRC prognosis. The mutation of KRAS indicated a poor prognosis of CRC patients. The current competing risk nomogram would help physicians to predict cancer specific death of CRC patients who had KRAS testing.

Keywords: Colorectal cancer; Competing risk; KRAS; Nomograms; Prognosis; SEER.

Grants and funding

This grant was supported by the National Natural Science Foundation of China (81372178; 81502386; 81772944; 81572715) and the High level health innovative talents program in Zhejiang and Natural Science Foundation of Zhejiang (LZ17H60003). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.