Prediction of CCND1 amplification using plasma DNA as a prognostic marker in oesophageal squamous cell carcinoma.
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ABSTRACT: Background
We aimed to develop a new biomarker to predict cyclin D1 (CCND1) status using plasma DNA in oesophageal squamous cell carcinoma (ESCC) patients.Methods
We evaluated the ratio of the CCND1 (11q13) dosage to the dopamine receptor D2 (DRD2; 11q22-23) dosage (C/D ratio) as CCND1 copy number. This study was divided into three steps: (1) Determination of a cutoff value for the C/D ratio in test scale; (2) Comparison of the C/D ratio in between plasma samples and cancer tissues in ESCC patients showing high plasma C/D ratio; (3) Validation study of the clinical application of the plasma C/D ratio as a diagnostic and prognostic marker, by comparing with clinicopathologic factors in 96 ESCC patients.Results
The plasma C/D ratio was significantly higher in the ESCC group than the controls (P=0.0134). A high plasma C/D ratio reflected the tumour C/D ratio, and significantly correlated with a poorer prognosis (P=0.0186). Moreover, the high C/D ratio was found to be an independent prognostic factor on multivariate analysis (P=0.0266; hazard ratio 5.988).Conclusion
Prediction of CCND1 amplification using plasma DNA is thought to be a promising prognostic biomarker in ESCC patients.
SUBMITTER: Takeshita H
PROVIDER: S-EPMC2865765 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundSeveral recent studies demonstrated that microRNAs are stably detectable in plasma/serum. We tested whether miR-18a, which is located in the miR-17-92 cluster and reported to be highly expressed in tissues of oesophageal squamous cell carcinoma (ESCC), served as a plasma biomarker in patients with ESCC.MethodsThis study was divided into three steps: (1) confirmation of higher miR-18a levels in primary ESCC tissues and cell lines than normal ESCC tissues and a human fibroblast cell line. (2) Evaluation of the plasma miR-18a assay using quantitative RT-PCR by comparing results from 106 consecutive patients with ESCC and 54 healthy volunteers. (3) Evaluation of the assay for monitoring tumour dynamics in patients with ESCC.Results(1) Expression of miR-18a was significantly higher in ESCC tissues (P=0.0020) and ESCC cell lines (P=0.0121) than normal tissues and fibroblasts. (2) Plasma concentrations of miR-18a were significantly higher in ESCC patients than healthy volunteers (P<0.0001; ESCC patients vs healthy volunteers (mean±s.d.): 11.77±13.45 vs 0.73±0.54 amol μl(-1)). The value of the area under the receiver-operating characteristic (ROC) curve (AUC) was 0.9449. Furthermore, the ROC curves to detect early ESCC such as pTis-1 and pStage0-I showed AUCs of 0.9479 and 0.9642, respectively. (3) Plasma levels of miR-18a were significantly lower in postoperative samples than preoperative samples (P=0.0076).ConclusionPlasma miR-18a may be a very useful biomarker for cancer detection and the monitoring of tumour dynamics in patients with ESCC.
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