Dataset Information

Circulating microRNAs in plasma of patients with oesophageal squamous cell carcinoma.

ABSTRACT:

Background

Several recent studies demonstrated that microRNAs (miRNAs) are stably detectable in plasma/serum. We hypothesised that plasma miRNAs concentrations contributed to potential biomarkers in patients with oesophageal squamous cell carcinoma (ESCC).

Methods

We selected three oncogenic miRNAs (miR-21, miR-184, miR-221) and one tumour suppressive miRNA (miR-375), which are frequently reported in squamous cell carcinoma, as candidate targets for this plasma miRNA assay. This study was divided into three steps: (1) Determination of appropriate plasma miRNAs in preliminary tests. (2) Evaluation of whether the plasma miRNA assays could monitor tumour dynamics. (3) Validation study on the clinical application of plasma miRNA assays in 50 ESCC patients and 20 healthy volunteers.

Results

(1) In preliminary tests, the plasma level of miR-21 was significantly higher (P=0.0218) and that of miR-375 (P=0.0052) was significantly lower in ESCC patients than controls. (2) The high plasma miR-21 levels reflected tumour levels in all cases (100%). The plasma level of miR-21 was significantly reduced in postoperative samples (P=0.0058). (3) On validation analysis, the plasma level of miR-21 tended to be higher in ESCC patients (P=0.0649), while that of miR-375 was significantly lower (P<0.0001) and the miR-21/miR-375 ratio was significantly higher (P<0.0001) in ESCC patients than in controls. The value of the area under the receiver-operating characteristic curve (AUC) was 0.816 for the miR-21/miR-375 ratio assay. Patients with a high plasma level of miR-21 tended to have greater vascular invasion (P=0.1554) and to show a high correlation with recurrence (P=0.0164).

Conclusion

Detection of circulating miRNAs might provide new complementary tumour markers for ESCC.

SUBMITTER: Komatsu S

PROVIDER: S-EPMC3137413 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundOesophageal squamous cell carcinoma (ESCC) is the predominant subtype of oesophageal carcinoma in China, with the overall 5-year survival rate of <10%. The current tumour-node-metastasis (TNM) staging system has become so complex that it is not easy to use in the life expectancy assessment. We aim to combine clinical variables and biomarkers to develop and validate a relative simple and reliable model, named the FENSAM, for ESCC prognosis.MethodsTo build the FENSAM, we analysed 22 potential prognostic factors from 461 patients, including 9 biomarkers (Ezrin, Fascin, desmocollin 2 (DSC2), pFascin, activating transcription factor 3 (ATF3), connective-tissue growth factor (CTGF), neutrophil gelatinase-associated lipocalin (NGAL), NGAL receptor (NGALR), and cysteine-rich angiogenic protein 61 (CYR61)) and other 13 clinical variables. We selected significant factors associated with survival of ESCC patients, and used them to build our FENSAM model. We then obtained the hazard risk score of the model to classify ESCC patients. In addition, we validated the model in an independent cohort of 290 patients from the same hospital. The predictive performance of the model was assessed by the Area under the Receiver Operating Characteristic Curve (AUC) and Kaplan-Meier survival analysis.ResultsWe found six markers significantly associated with survival of ESCC patients (Ezrin, Fascin, ATF3, surgery extent, N-stage, and M-stage). They were combined to create a novel four-stage FENSAM model for patients' classification. FENSAM possessed a high classification precision similar to the TNM staging system, but with a much simpler model. The efficiency of FENSAM was evaluated by different quantiles of AUC and the results of survival analysis. The validation result demonstrated the potential of the FENSAM model to improve classification accuracy for ESCC patients.ConclusionsFENSAM provides an alternative classifier for ESCC patients with a high classification precision using a simple model.