Sentinel Lymph Node Genes to Predict Prognosis in Node-Positive Melanoma Patients.
OBJECTIVE
Melanoma patients with a single microscopically-positive sentinel lymph node (SLN) are classified as stage III and are often advised to undergo expensive and substantially toxic adjuvant therapy. However, the 5-year survival rate for these patients, with or without adjuvant therapy, varies from 14 to 85 %, representing a heterogeneous biological population with a variable prognosis. We aimed to identify an SLN gene signature to aid in risk stratification of patients with tumor-positive SLNs.


METHODS
Microarray experiments were performed to screen SLN genes in recurrence (N = 39) versus non-recurrence (N = 58) groups in the training dataset. Quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) assay was applied to confirm the expression of selected SLN genes, which were further verified using an independent validation cohort (N = 30). Area under the receiver operating characteristic curve (AUC) was calculated to evaluate prognostic accuracy of the selected SLN gene panel, and the prognostic value of our SLN gene signature was also compared with the current American Joint Committee on Cancer (AJCC) staging system.


RESULTS
We identified two SLN genes (PIGR and TFAP2A) that provided high prognostic accuracy in SLN-positive melanoma patients (AUC = 0.864). These two SLN genes, along with clinicopathological features, can differentiate the high- and low-risk groups in node-positive melanoma patients in this cohort.


CONCLUSIONS
The two SLN genes, when combined with clinicopathological features, may offer a new tool for personalized patient risk assessment.
Department of Surgery, University of Louisville School of Medicine, Louisville, KY, USA.
Hongying
H
Hao
Department of Surgery, University of Louisville School of Medicine, Louisville, KY, USA.
Deyi
D
Xiao
Biostatistics Shared Facility, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA.
Jianmin
J
Pan
Department of Surgery, University of Louisville School of Medicine, Louisville, KY, USA.
Jifu
J
Qu
Department of Surgery, University of Louisville School of Medicine, Louisville, KY, USA.
Michael
M
Egger
Genomics Facility, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA.
Sabine
S
Waigel
Department of Pathology, University of Louisville School of Medicine, Louisville, KY, USA.
Mary Ann G
MA
Sanders
Genomics Facility, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA.|Department of Medicine and Department of Pharmacology and Toxicology, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA.
Wolfgang
W
Zacharias
Biostatistics Shared Facility, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA.
Shesh N
SN
Rai
Department of Surgery, University of Louisville School of Medicine, Louisville, KY, USA. mcmasters@louisville.edu.
Kelly M
KM
McMasters
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis / Q000473:pathology*; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology*; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D019056:Receptors, Polymeric Immunoglobulin / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D000071036:Sentinel Lymph Node / Q000473:pathology*; D021701:Sentinel Lymph Node Biopsy; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology*; D015996:Survival Rate; D050656:Transcription Factor AP-2 / Q000235:genetics*
D019056:Receptors, Polymeric Immunoglobulin; C493673:TFAP2A protein, human; D050656:Transcription Factor AP-2