Identification of Hyper-Methylated Tumor Suppressor Genes-Based Diagnostic Panel for Esophageal Squamous Cell Carcinoma (ESCC) in a Chinese Han Population

Frontiers in Genetics
Chenji WangMinghua Wang

Abstract

DNA methylation-based biomarkers were suggested to be promising for early cancer diagnosis. However, DNA methylation-based biomarkers for esophageal squamous cell carcinoma (ESCC), especially in Chinese Han populations have not been identified and evaluated quantitatively. Candidate tumor suppressor genes (N = 65) were selected through literature searching and four public high-throughput DNA methylation microarray datasets including 136 samples totally were collected for initial confirmation. Targeted bisulfite sequencing was applied in an independent cohort of 94 pairs of ESCC and normal tissues from a Chinese Han population for eventual validation. We applied nine different classification algorithms for the prediction to evaluate to the prediction performance. ADHFE1, EOMES, SALL1 and TFPI2 were identified and validated in the ESCC samples from a Chinese Han population. All four candidate regions were validated to be significantly hyper-methylated in ESCC samples through Wilcoxon rank-sum test (ADHFE1, P = 1.7 × 10-3; EOMES, P = 2.9 × 10-9; SALL1, P = 3.9 × 10-7; TFPI2, p = 3.4 × 10-6). Logistic regression based prediction model shown a moderately ESCC classification performance (Sensitivity = 66%, Specificity = 87%, AUC = 0....Continue Reading

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Datasets Mentioned

BETA
GSE74693
GSE79366
GSE53045
GSE36054
GSE42861
EGAS00001003158

Methods Mentioned

BETA
PCA
PCR
surgical resection
electrophoresis

Software Mentioned

randomForest
custom
R
Package
ComBat
BSseeker2
PolyT
nnet
stats

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