Exploratory Biomarker Analysis for Treatment Response in KRAS Wild Type Metastatic Colorectal Cancer Patients Who Received Cetuximab Plus Irinotecan

Overview

Journal BMC Cancer

Publisher Biomed Central

Specialty Oncology

Date 2015 Oct 22

PMID 26486455

Citations 9

Authors

Seung Tae Kim

Tae Jin Ahn

Eunjin Lee

In-Gu Do

Su Jin Lee

Se Hoon Park

Joon Oh Park

Young Suk Park

Ho Yeong Lim

Won Ki Kang

Suk Hyeong Kim

Jeeyun Lee

Hee Cheol Kim

Affiliations

Soon will be listed here.

Abstract

Background: More than half of the patients selected based on KRAS mutation status fail to respond to the treatment with cetuximab in metastatic colorectal cancer (mCRC). We designed a study to identify additional biomarkers that could act as indicators for cetuximab treatment in mCRC.

Methods: We investigated 58 tumor samples from wild type KRAS CRC patients treated with cetuximab plus irinotecan (CI). We conducted the genotyping for mutations in either BRAF or PIK3CA and profiled comprehensively the expression of 522 kinase genes.

Results: BRAF mutation was detected in 5.1 % (3/58) of patients. All 50 patients showed wild type PIK3CA. Gene expression patterns that categorized patients with or without the disease control to CI were compared by supervised classification analysis. PSKH1, TLK2 and PHKG2 were overexpressed significantly in patients with the disease control to IC. The higher expression value of PSKH1 (r = 0.462, p < 0.001) and TLK2 (r = 0.361, p = 0.005) had the significant correlation to prolonged PFS.

Conclusion: The result of this work demonstrated that expression nature of kinase genes such as PSKH1, TLK2 and PHKG2 may be informative to predict the efficacy of CI in wild type KRAS CRC. Mutations in either BRAF or PIK3CA were rare subsets in wild type KRAS CRC.

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