Molecular markers in circulating tumour cells from metastatic colorectal cancer patients

Paola Gazzaniga, Angela Gradilone, Arianna Petracca, Chiara Nicolazzo, Cristina Raimondi, Roberto Iacovelli, Giuseppe Naso, Enrico Cortesi

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)2073-2077
Number of pages5
JournalJournal of Cellular and Molecular Medicine
Volume14
Issue number8
DOIs
Publication statusPublished - Aug 2010

Keywords

  • Aldheyde dehydrogenase 1 survivin
  • Circulating tumour cells
  • Colorectal cancer
  • Drug resistance
  • Multidrug resistance related protein 5

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine

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