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. 2019 Mar 29;11(4):446. doi: 10.3390/cancers11040446

Table 3.

Ion channels genes showing very high discriminating ability (AUC > 0.90) in the Talantov dataset were validated in a first round validation in the Raskin dataset. Genes passing the first validation were then validated in the Riker dataset. Genes passing screening phase and all two validations were searched in Pubmed to identify those never directly related to melanoma. Genes showing 0 value in the “Novelty” column are genes never related to melanoma according to Pubmed abstract. Five genes were selected according to this procedure (SCNN1A, GJB3, KCNK7, GJB1, KCNN2). Empty cells indicate lack of validation.

No. Gene Name Screening Phase (in the Talantov Dataset, GEO, GDS1375) First-Round Validation (in the Raskin Dataset, GEO GSE15605) * Second-Round Validation (in the Riker Dataset, Oncomine) ** Novelty (in PubMeds Abstracts) *** Full in Silico Validation
63 Patients 62 Patients 59 Patients
t Test
Melanoma vs. Nevi		 Ratio Melan. vs. Nevi AUC Validation on AUC Value * Validation on Ratio Value Gene Name and Melanoma Words Co-Occurrence
1 SCNN1A 1.0 × 10−14 0.07 0.98 Yes (0.85) Yes (−4.94) 0 graphic file with name cancers-11-00446-i003.jpg
2 ANO1 8.6 × 10−18 0.231 0.98 Yes (0.87)
3 GJA1 2.1 × 10−9 0.086 0.98 Yes (0.88)
4 GJB5 3.4 × 10−13 0.1277 0.97
5 GJB3 2.1 × 10−10 0.2453 0.96 Yes (0.86) Yes (−6.662) 0 graphic file with name cancers-11-00446-i003.jpg
6 AQP3 6.9 × 10−7 0.067 0.97
7 SCNN1B 1.4 × 10−14 0.313 0.96 Yes (0.87)
8 VDAC1 2.0 × 10−10 1.8 0.96
9 CLIC1 1.9 × 10−12 1.738 0.96
10 GABRE 2.3 × 10−13 0.203 0.95 Yes (0.88) Yes (−3.162) ≥1
11 KCNK7 1.8 × 10−17 0.081 0.94 Yes (0.86) Yes (−2.832) 0 graphic file with name cancers-11-00446-i003.jpg
12 KCND3 2.0 × 10−11 0.487 0.94 Yes (0.89)
14 KCNN4 1.5 × 10−6 3.79 0.93
13 ITPR3 1.1 × 10−9 2.311 0.93
15 KCNK1 8.6 × 10−11 0.269 0.93 Yes (0.89)
16 KCNS3 7.7 × 10−6 0.403 0.93
17 TRPM2 6.5 × 10−5 0.219 0.93
18 GRIA1 8.7 × 10−11 0.1049 0.93
19 GJB1 3.4 × 10−8 2.643 0.93 Yes (0.87) Yes (3.303) 0 graphic file with name cancers-11-00446-i003.jpg
20 KCNN2 3.6 × 10−10 4.337 0.91 Yes (0.91) Yes (2.284) 0 graphic file with name cancers-11-00446-i003.jpg

* validation in GSE15605 was considered effective if AUC > 0.85 (AUC is reported in parenthesis); ** validation in Riker dataset was considered effective if difference of melanoma vs. normal skin is <0.5 or >1.5 (difference is reported in parenthesis, calculated from log2 median-centered intensity according to Oncomine); *** Novelty was assessed onto the five genes validated in the first and second validations steps.