Circulating miR-200c as a diagnostic and prognostic biomarker for gastric cancer

Journal of Translational Medicine

Lourdes Calvo⁴  Luis Miguel Antón-Aparicio³  Angélica Figueroa⁴  Alberto Carral⁴  Maria Quindós⁴  Juan Fernández-Tajes²  Moisés Blanco⁴  Isabel Santamarina⁴  Mar Haz⁴  Maria José Lorenzo-Patiño¹  Pilar Iglesias-Díaz¹  Vanessa Medina-Villaamil⁴  Margarita Reboredo⁴  Manuel Valladares-Ayerbes⁴ 

[1] Pathology Department, La Coruña University Hospital, Servicio Galego de Saúde (SERGAS), As Xubias, 84, La Coruña, PC, 15006, Spain;Genomic Group, INIBIC- Biomedical Research Institute (INIBIC), Carretera del Pasaje, s/n, La Coruña, PC, 15006, Spain;Medicine Department, La Coruña University (UDC), Campus de Oza, s/n, La Coruña, PC, 15006, Spain;Translational Cancer Research Lab, Biomedical Research Institute (INIBIC), Carretera del Pasaje, s/n, La Coruña, PC, 15006, Spain

关键词: Prognostic factors;    Biomarker;    Blood;    miR-200;    MicroRNA;    Gastric cancer;   

Others  :  829685
DOI  :  10.1186/1479-5876-10-186

 received in 2012-05-28, accepted in 2012-08-31,  发布年份 2012

【 摘 要 】

Background

MicroRNAs are aberrantly expressed and correlate with tumourigenesis and the progression of solid tumours. The miR-200 family determines the epithelial phenotype of cancer cells and regulates invasiveness and migration. Thus, we hypothesised that the quantitative detection of the miR-200 family as epithelial-specific microRNAs in the blood could be a useful clinical biomarker for gastric cancer (GC).

Methods

We initially validated the expression levels of miR-200a, 200b, 200c and 141 in GC cell lines (n = 2) and blood from healthy controls (n = 19) using real-time quantitative reverse transcription PCR (qRT-PCR). The microarray expression profiles of the miR-200 family in 160 paired samples of non-tumour gastric mucosae and GC were downloaded through ArrayExpress and analysed. MiR-200c was selected for clinical validation. The qRT-PCR prospective assessment of miR-200c was performed using 67 blood samples (52 stage I-IV GC patients and 15 controls); the area under the receiver operating characteristic curve (AUC-ROC) was estimated. The Kaplan-Meier and Breslow-Wilcoxon tests were used to assess the correlation of miR-200c with overall and progression-free survival (OS and PFS). Multivariate analyses were performed using the Cox model.

Results

The miR-200c blood expression levels in GC patients were significantly higher than in normal controls (p = 0.018). The AUC-ROC was 0.715 (p = 0.012). The sensitivity, specificity and accuracy rates of 65.4%, 100% and 73.1%, respectively, were observed. The levels of miR-200c in the blood above the cutoff defined by the ROC curve was found in 17.6% of stage I-II GC patients, 20.6% of stage III patients and 67.7% of stage IV patients (p < 0.001). The miR-200c expression levels were not associated with clinical or pathological characteristics or recent surgical procedures. There was a correlation (p = 0.016) with the number of lymph node metastases and the increased expression levels of miR-200c in blood were significantly associated with a poor OS (median OS, 9 vs 24 months; p = 0.016) and PFS (median PFS, 4 vs 11 months; p = 0.044). Multivariate analyses confirmed that the upregulation of miR-200c in the blood was associated with OS (HR = 2.24; p = 0.028) and PFS (HR = 2.27; p = 0.028), independent of clinical covariates.

Conclusions

These data suggest that increased miR-200c levels are detected in the blood of gastric cancer patients. MiR-200c has the potential to be a predictor of progression and survival.

【 授权许可】

   
2012 Valladares-Ayerbes et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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