title: A multimarker panel for circulating tumor cells detection predicts patient outcome and therapy response in metastatic colorectal cancer.
abstract: 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.
authors.affiliation: Translational Medical Oncology Laboratory, Health Research Institute of Santiago (IDIS), SERGAS, Santiago de Compostela, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Barbazán
authors.forename: Laura
authors.initials: L
authors.lastname: Muinelo-Romay
authors.forename: María
authors.initials: M
authors.lastname: Vieito
authors.forename: Sonia
authors.initials: S
authors.lastname: Candamio
authors.forename: Antonio
authors.initials: A
authors.lastname: Díaz-López
authors.forename: Amparo
authors.initials: A
authors.lastname: Cano
authors.forename: Antonio
authors.initials: A
authors.lastname: Gómez-Tato
authors.forename: María de los Ángeles
authors.initials: Mde L
authors.lastname: Casares de Cal
authors.forename: Miguel
authors.initials: M
authors.lastname: Abal
authors.forename: Rafael
authors.initials: R
authors.lastname: López-López
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D014408:Biomarkers, Tumor / Q000032:analysis*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000069287:Capecitabine; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D005500:Follow-Up Studies; D006801:Humans; D000077146:Irinotecan; D008113:Liver Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000401:mortality / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011379:Prognosis; D015996:Survival Rate
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000068258:Bevacizumab; D000069287:Capecitabine; D000077146:Irinotecan; D000068818:Cetuximab; D005472:Fluorouracil; D002166:Camptothecin
keywords: biomarkers; circulating tumor cells; epithelial to mesenchymal transition; metastatic colorectal cancer; patient outcome; therapy response