A multimarker panel for circulating tumor cells detection predicts patient outcome and therapy response in metastatic colorectal cancer

Circulating tumor cells (CTCs), proposed as major players in cancer dissemination, have demonstrated clinical prognostic significance in several cancer types. However, their predictive value remains unclear. Here we evaluated the clinical utility of six CTC markers (tissue specific and epithelial to mesenchymal transition transcripts) both as prognostic and predictive tools in metastatic colorectal cancer (mCRC) patients. CTCs were immunoisolated from blood in 50 mCRC patients at baseline and at 4 and 16 weeks after treatment onset. Expression levels of GAPDH, VIL1, CLU, TIMP1, LOXL3 and ZEB2 were determined by qualitative polymerase chain reaction and normalized to the unspecific cell isolation marker CD45. At baseline, median progression‐free survival (PFS) and overall survival (OS) for patients with high CTC markers were 6.3 and 12.7 months, respectively, versus 12.7 and 24.2 for patients with low CTC markers (PFS; p = 0.0003; OS; p = 0.044). Concerning response to therapy, PFS and OS for patients with increased CTC markers along treatment were, respectively, 6.6 and 13.1 months, compared with 12.7 and 24.3 for patients presenting CTC markers reduction (PFS; p = 0.004; OS; p = 0.007). Of note, CTC markers identified therapy‐refractory patients not detected by standard image techniques. Patients with increased CTC markers along treatment, but classified as responders by computed tomography, showed significantly shorter survival times (PFS: 7.8 vs. 13.2; OS: 14.4 vs. 24.4; months). In conclusion, we have generated a CTC marker panel for prognosis evaluation and the identification of patients benefiting or not from therapy in mCRC. Our methodology efficiently classified patients earlier than routine computed tomography and from a minimally invasive liquid biopsy. What's new? Circulating tumor cells (CTC) play a critical role in disseminating the primary tumor to distant metastases. In colorectal cancer, CTC quantification is used as prognostic marker for disease outcome. Here, the authors tested a panel of tissue‐specific and epithelial‐to‐mesenchymal transition transcripts (GAPDH, VIL1, CLU, TIMP1, LOXL3, ZEB2) in isolated CTCs to improve the prognostic value in patients with metastatic colorectal cancer. High CTC marker expression correlated inversely with patient survival, both before and during treatment, and was a better predictor of patient outcome than standard computed tomography. These data underscore the importance of CTCs and CTC‐derived biomark