title: Molecular markers in circulating tumour cells from metastatic colorectal cancer patients.
abstract: The prognosis of metastatic cancer patients is still largely affected by treatment failure, mainly due to drug resistance. The hypothesis that chemotherapy might miss circulating tumour cells (CTCs) and particularly a subpopulation of more aggressive, stem-like CTCs, characterized by multidrug resistance, has been recently raised. We investigated the prognostic value of drug resistance and stemness markers in CTCs from metastatic colorectal cancer patients treated with oxaliplatin (L-OHP) and 5-fluoruracil (5-FU) based regimens. Forty patients with metastatic colorectal cancer were enrolled. CTCs were isolated from peripheral blood and analysed for the expression of aldheyde dehydrogenase 1 (ALDH1), CD44, CD133 (used as markers of stemness), multidrug resistance related protein 5 (MRP5 used as marker of resistance to 5-FU and L-OHP) and survivin (used as a marker of apoptosis resistance). CTCs were found in 27/40 (67%) patients. No correlation was found between the expression of either CD44 and CD133 in CTCs and the outcome of patients, while a statistically significant shorter progression-free survival was found in patients with CTCs positive for the expression of ALDH1, survivin and MRP5. These results support the idea that isolating survivin and MRP5+ CTCs may help in the selection of metastatic colorectal cancer patients resistant to standard 5-FU and L-OHP based chemotherapy, for which alternative regimens may be appropriate.
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Italy. paola.gazzaniga@uniroma1.it
authors.forename: Paola
authors.initials: P
authors.lastname: Gazzaniga
authors.forename: Angela
authors.initials: A
authors.lastname: Gradilone
authors.forename: Arianna
authors.initials: A
authors.lastname: Petracca
authors.forename: Chiara
authors.initials: C
authors.lastname: Nicolazzo
authors.forename: Cristina
authors.initials: C
authors.lastname: Raimondi
authors.forename: Roberto
authors.initials: R
authors.lastname: Iacovelli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Naso
authors.forename: Enrico
authors.initials: E
authors.lastname: Cortesi
mesh_terms: D000071916:AC133 Antigen; D000444:Aldehyde Dehydrogenase / Q000235:genetics; D000080924:Aldehyde Dehydrogenase 1 Family; D015703:Antigens, CD / Q000235:genetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000008:administration & dosage; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics; D051034:Inhibitor of Apoptosis Proteins; D007527:Isoenzymes / Q000235:genetics; D053208:Kaplan-Meier Estimate; D008869:Microtubule-Associated Proteins / Q000235:genetics; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000378:metabolism* / Q000473:pathology; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010455:Peptides / Q000235:genetics; D050697:Retinal Dehydrogenase; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin; D016896:Treatment Outcome
chemical_list: D000071916:AC133 Antigen; D000444:Aldehyde Dehydrogenase; D000080924:Aldehyde Dehydrogenase 1 Family; D015703:Antigens, CD; D014408:Biomarkers, Tumor; D005472:Fluorouracil; D006023:Glycoproteins; D018960:Hyaluronan Receptors; D051034:Inhibitor of Apoptosis Proteins; D007527:Isoenzymes; D008869:Microtubule-Associated Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D010455:Peptides; D050697:Retinal Dehydrogenase; D000077022:Survivin; C120809:ABCC5 protein, human; C107489:BIRC5 protein, human; C000606023:PROM1 protein, human; C510223:ALDH1A1 protein, human