A Prognostic Gene Signature Expressed in Primary Cutaneous Melanoma: Synergism With Conventional Staging

JNCI Cancer Spectrum

Heinecke, Achim¹  Brunner, Georg²  Suter, Ludwig²  Schulze, Hans-Joachim³  Berking, Carola⁴  Atzpodien, Jens⁵  Blödorn-Schlicht, Norbert⁶  Falk, Thomas M⁶  Ertas, Beyhan⁶ 

[1] Department of Biometry and Clinical Research, Westphalian Wilhelms University, Muenster, Germany;Department of Cancer Research;Department of Dermatology, Skin Cancer Center Hornheide, Muenster, Germany;Department of Dermatology, University Hospital, Munich, Germany;Department of Medical Oncology, Niels Stensen Clinics, Osnabrück, Germany;Dermatologikum Hamburg, Hamburg, Germany

关键词: gene expression profiling;    melanoma;    patient prognosis;    malignant melanoma, cutaneous;    genes;    neoplasms;    polymerase chain reaction;   

DOI  :  10.1093/jncics/pky032

学科分类：肿瘤学

来源: Oxford University Press

【 摘 要 】

BackgroundCurrent clinico-pathological American Joint Committee on Cancer (AJCC) staging of primary cutaneous melanoma is limited in its ability to determine clinical outcome, and complementary biomarkers are not available for routine prognostic assessment. We therefore adapted a gene signature, previously identified in fresh-frozen (FF) melanomas and adjacent stroma, to formalin-fixed paraffin-embedded (FFPE) melanomas. The aim was to develop a gene expression profiling (GEP) score to define patient survival probability at the time of first diagnosis.MethodsExpression of 11 FF melanoma signature genes was quantified by reverse transcription polymerase chain reaction in an FFPE melanoma training cohort (n = 125), corresponding to the combined FF melanoma training and validation cohorts. The resulting GEP score was validated technically and clinically in an independent FFPE melanoma cohort (n = 211). All statistical tests were two-sided.ResultsWe identified a prognostic eight-gene signature in the tumor area (tumor and adjacent tissue) of AJCC stage I–III melanomas. A signature-based GEP score correlated with melanoma-specific survival (MSS; Kaplan-Meier analysis: P < .0001) was independent of tumor stage (multivariable regression analysis: P = .0032) and stroma content (<5%–90%) and complemented conventional AJCC staging (receiver operating characteristic curve analysis: area under the curve = 0.91). In the clinical validation cohort, the GEP score remained statistically significant (P = .0131) in a multivariable analysis accounting for conventional staging. The GEP score was technically robust (reproducibility: 93%; n = 84) and clinically useful, as a binary as well as a continuous score, in predicting stage-specific patient MSS.ConclusionsThe GEP score is a clinically significant prognostic tool, contributes additional information regarding the MSS of melanoma patients, and complements conventional staging.

【 授权许可】

CC BY-NC-ND