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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.

Exploratory biomarker analysis for treatment response in KRAS wild type metastatic colorectal cancer patients who received cetuximab plus irinotecan