Protein biomarkers are widely used in
cancer diagnosis, prognosis, and prediction of treatment response. Here we introduce the use of targeted multiplex proteomics (
TMP) as a tool to simultaneously measure a panel of 54
proteins involved in oncogenic, tumour suppression, drug metabolism and resistance, in patients with metastatic
colorectal cancer (mCRC).
TMP provided valuable diagnostic information by unmasking an occult neuroendocrine differentiation and identifying a misclassified case based on abnormal
proteins phenotype. No significant differences in
protein levels between unpaired primary and metastatic samples were observed. Four
proteins were found differentially expressed in KRAS-mutant as compared to wild-type tumours (overexpressed in mutant: KRAS, EGFR; overexpressed in wild-type: TOPO1, TOP2A). Survival analyses revealed the association between
mesothelin expression and poor overall survival, whereas lack of
PTEN protein expression associated with lower progression-free survival with anti-EGFR-based
therapy in the first-line setting for patients with RAS wild-type tumour. Finally, outlier analysis identified putative targetable
proteins in 65% of patients lacking a targetable genomic alteration. Our data show that
TMP constitutes a promising, novel molecular prescreening tool in mCRC to identify
protein expression alterations that may impact on patient outcomes and more precisely guide patient eligibility to clinical trials with novel targeted
experimental therapies.