Plasma YKL-40 as a biomarker for poor prognosis in patients with metastatic colorectal cancer treated with 3. line cetuximab and irinotecan

Background

YKL-40 (CHI3L1) plays a major role in inflammation and angiogenesis. In patients with metastatic colorectal cancer (mCRC) we wanted to test if high pretreatment levels of plasma YKL-40 and change of YKL-40 during therapy with cetuximab and irinotecan was independent of KRAS mutation status and associated with progression free (PFS) and overall survival (OS).

Methods

Two independent studies of 162 patients and 98 patients (Study I and II) with mCRC resistant to 5-FU, oxaliplatin and irinotecan treated with cetuximab and irinotecan without knowledge of their KRAS mutation status were performed in Denmark between 2006 and 2008. Plasma YKL-40 was determined by ELISA. Seven mutations in the KRAS oncogene were determined by the DxS TheraScreen kit.

Results

In both studies a high pretreatment plasmaYKL-40 (log transformed continuous variable) was significantly associated to short overall survival (OS) independent of KRAS mutation status (Study I: HR = 1.17, 95% CI 1.04-1.30, P = 0.009; interaction between KRAS and YKL-40 P = 0.75; Study II: HR = 1.34, 95% CI 1.12-1.59, P = 0.0001; interaction between KRAS and YKL-40 p = 0.85). Multivariate Cox analysis including YKL-40, age, sex, performance status (PS), number of metastatic sites and KRAS mutation status demonstrated that elevated pretreatment plasma YKL-40 was an independent biomarker of OS (Study I: HR = 1.53, 95% CI 1.10-2.13, P = 0.013; Study II: HR = 2.89, 1.84-4.53, P 

Conclusions

In two independent studies plasma YKL-40 before and during treatment of patients with mCRC with cetuximab and irinotecan was a strong independent biomarker of PFS and OS independent of KRAS mutation status.

Clinical trial identification

EudraCT number 2006-001-961-40

Legal entity responsible for the study

Department of Oncology, Herlev and Gentofte Hospital, University of Copenhagen

Funding

Department of Oncology, Herlev and Gentofte Hospital, University of Copenhagen

Disclosure

All authors have declared no conflicts of interest.