A specific KRAS codon 13 mutation is an independent predictor for colorectal cancer metachronous distant metastases

Qingyang Feng; Li Liang; Li Ren; Jingwen Chen; Ye Wei; Wenju Chang; Dexiang Zhu; Qi Lin; Peng Zheng; Jianmin Xu

A specific KRAS codon 13 mutation is an independent predictor for colorectal cancer metachronous distant metastases

Am J Cancer Res. 2015 Jan 15;5(2):674-88. eCollection 2015.

Authors

Qingyang Feng¹, Li Liang², Li Ren¹, Jingwen Chen¹, Ye Wei¹, Wenju Chang¹, Dexiang Zhu¹, Qi Lin¹, Peng Zheng¹, Jianmin Xu¹

Affiliations

¹ Department of General Surgery, Zhongshan Hospital, Fudan University Shanghai, China.
² Department of Internal Medicine/Oncology, Zhongshan Hospital, Fudan University Shanghai, China.

PMID: 25973306
PMCID: PMC4396022

Abstract

Background: In colorectal cancer, there are significant differences between synchronous and metachronous distant metastases. However in recent studies, synchronous and metachronous metastases were always lumped together, neglecting their clinical and molecular differences. The mechanism of the latency of metachronous metastases is still unclear. We conducted this study to reveal the relationship between EGFR pathways and metachronous metastases, and try to find efficient predictors.

Methods: PCRs and pyrosequencing were used to detect KRAS, BRAF, PIK3CA and PTEN mutations in primary tumor tissues in a total of 281 patients from 2002 to 2008. Patients were identified into three groups: no-metastases group, synchronous-metastases group and metachronous-metastases group. Clinical and survival data were collected from a prospective database.

Results: KRAS codon 13 mutation was an independent predictor only for metachronous distant metastases (OR = 11.857, P < 0.001), but not for synchronous metastases. Male gender (OR = 2.233, P = 0.024), primary tumor located at rectum (OR = 0.404, P = 0.041), and primary pN2 stage (OR = 3.361, P = 0.01) were also independent predictors for metachronous distant metastases. Different SNPs in KRAS worked significantly different in determining synchronous or metachronous metastases. BRAF mutation (Univariate, OR = 11.5, P = 0.039) and > 200 ng/ml preoperative CEA (Univariate, OR = 41, P = 0.011) potentially predicted metastases within 6 months after primary tumor resection. After metachronous metastases, radical resection (HR = 0.280, P = 0.002) was the most important protective factor for long-term survival.

Conclusion: There were significant clinical and molecular differences between synchronous and metachronous metastases. As an independent predictor, KRAS codon 13 mutation might be the key to explain the mechanism of colorectal cancer metachronous distant metastases. Together with clinical characteristics, it could aid in the early detection of metachronous metastases.

Keywords: Colorectal cancer; KRAS mutation; metachronous metastases; predictor.