A time course-dependent metastatic gene expression signature predicts outcome in human metastatic melanomas

Diagnostic Pathology

Jiaxi Lin¹  Nan Li¹  Ying Zhou¹  Guoxue Zhang¹  Rongyi Chen¹ 

[1] Department of Dermatology, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China

关键词: Gene signature;    Prediction;    Prognosis;    Metastasis;    Melanomas;   

Others  :  1150023
DOI  :  10.1186/s13000-014-0155-2

 received in 2014-05-13, accepted in 2014-07-29,  发布年份 2014

【 摘 要 】

Background

The prognosis of patients with metastatic melanomas is extremely heterogeneous. Therefore, identifying high-risk subgroups by using innovative prediction models would help to improve selection of appropriate management options.

Methods

In this study, two datasets (GSE7929 and GSE7956) of mRNA expression microarray in an animal melanoma model were normalized by frozen Robust Multi-Array Analysis and then combined by the distance-weighted discrimination method to identify time course-dependent metastasis-related gene signatures by Biometric Research Branch-ArrayTools (BRB)-ArrayTools. Then two datasets (GSE8401 and GSE19234) of clinical melanoma samples with relevant clinical and survival data were used to validate the prognosis signature.

Results

A novel 192-gene set that varies significantly in parallel with the increasing of metastatic potentials was identified in the animal melanoma model. Further, this gene signature was validated to correlate with poor prognosis of human metastatic melanomas but not of primary melanomas in two independent datasets. Furthermore, multivariate Cox proportional hazards regression analyses demonstrated that the prognostic value of the 192-gene set is independent of the TNM stage and has higher areas under the receiver operating characteristic curve than stage information in both validation datasets.

Conclusion

Our findings suggest that a time course-dependent metastasis-related gene expression signature is useful in predicting survival of malignant melanomas and might be useful in informing treatment decisions for these patients.

【 授权许可】

   
2014 Chen et al.; licensee BioMed Central Ltd.

【 图 表 】

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