Int. J. Mol. Sci. 2012, 13(4), 4367-4387; doi:10.3390/ijms13044367
Evaluation of the Adenocarcinoma-Associated Gene AGR2 and the Intestinal Stem Cell Marker LGR5 as Biomarkers in Colorectal Cancer
1
Medical Oncology Department, La Coruña University Hospital, Servicio Galego de Saúde (SERGAS), As Xubias, 84. PC 15006, La Coruña, Spain
2
Translational Cancer Research Lab, Biomedical Research Institute (INIBIC), Carretera del Pasaje, s/n. PC 15006, La Coruña, Spain
3
Pathology Department, La Coruña University Hospital, Servicio Galego de Saúde (SERGAS), As Xubias, 84. PC 15006, La Coruña, Spain
4
Tissue Engineering and Cellular Therapy Lab, INIBIC, Carretera del Pasaje, s/n. PC 15006, La Coruña, Spain
5
Medicine Department, La Coruña University (UDC), Campus de Oza, s/n, PC 15006, La Coruña, Spain
6
Biostatistics and Clinical Epidemiology Unit, La Coruña University Hospital, Servicio Galego de Saúde (SERGAS), As Xubias 84, PC 15006, La Coruña, Spain
*
Author to whom correspondence should be addressed.
Received: 1 March 2012 / Revised: 20 March 2012 / Accepted: 23 March 2012 / Published: 5 April 2012
(This article belongs to the Special Issue Advances in Molecular Oncology (special issue))
Abstract
We aim to estimate the diagnostic performances of anterior gradient homolog-2 (AGR2) and Leucine-rich repeat-containing-G-protein-coupled receptor 5 (LGR5) in peripheral blood (PB) as mRNA biomarkers in colorectal cancer (CRC) and to explore their prognostic significance. Real-time PCR was used to analyze AGR2 and LGR5 in 54 stages I-IV CRC patients and 19 controls. Both mRNAs were significantly increased in PB from CRC patients compared to controls. The area under the receiver-operating characteristic curves were 0.722 (p = 0.006), 0.376 (p = 0.123) and 0.767 (p = 0.001) for AGR2, LGR5 and combined AGR2/LGR5, respectively. The AGR2/LGR5 assay resulted in 67.4% sensitivity and 94.7% specificity. AGR2 correlated with pT3–pT4 and high-grade tumors. LGR5 correlated with metastasis, R2 resections and high-grade. The progression-free survival (PFS) of patients with high AGR2 was reduced (p = 0.037; HR, 2.32), also in the stage I-III subgroup (p = 0.046). LGR5 indicated a poor prognosis regarding both PFS (p = 0.007; HR, 1.013) and overall survival (p = 0.045; HR, 1.01). High AGR2/LGR5 was associated with poor PFS (p = 0.014; HR, 2.8) by multivariate analysis. Our findings indicate that the assessment of AGR2 and LGR5 in PB might reflect the presence of circulating tumor cells (CTC) and stem cell like CTC in CRC. Increased AGR2 and LGR5 are associated with poor outcomes.Keywords:
colorectal cancer; real-time PCR; circulating tumor cells; prognostic markers; stem cells; anterior gradient homolog-2; leucine-rich repeat-containing G-protein-coupled receptor 5
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
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Valladares-Ayerbes, M.; Blanco-Calvo, M.; Reboredo, M.; Lorenzo-Patiño, M.J.; Iglesias-Díaz, P.; Haz, M.; Díaz-Prado, S.; Medina, V.; Santamarina, I.; Pértega, S.; Figueroa, A.; Antón-Aparicio, L.M. Evaluation of the Adenocarcinoma-Associated Gene AGR2 and the Intestinal Stem Cell Marker LGR5 as Biomarkers in Colorectal Cancer. Int. J. Mol. Sci. 2012, 13, 4367-4387.
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