Year-end Sale % OFF 
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 = 0.81). Moreover, advanced classification method had better performances (random forest and naive Bayes). Interestingly, the diagnostic performance could be improved in non-alcohol use subgroup (AUC = 0.84). In conclusion, our data demonstrate the methylation panel of ADHFE1, EOMES, SALL1 and TFPI2 could be an effective methylation-based diagnostic assay for ESCC.
Highlights
Esophageal cancer is one of the most aggressive malignant tumors with high prevalence and poor prognosis worldwide (Siegel et al, 2016)
We found that The Cancer Genome Atlas (TCGA) project has quantified the methylation profiles of 84 esophageal squamous cell carcinoma (ESCC) and 3 normal tissues, as well as 78 esophageal adenocarcinoma (EAC) and 13 normal tissues
Though some of the six CpG sites did not reach the statistical significance threshold due to the limited sample size, we still believed that all of these 6 CpG sites may be of potential as the non-invasive potential biomarkers for ESCC and were included for validation
Summary
Esophageal cancer is one of the most aggressive malignant tumors with high prevalence and poor prognosis worldwide (Siegel et al, 2016). Esophageal cancer usually occurs as two subtypes, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), which differed significantly in pathogenesis, pathology, epidemiology and geographical distribution (Enzinger and Mayer, 2003). The prevalence of ESCC and EAC in these regions are significantly unbalanced with 90% of esophageal cancer patients are ESCCs (Jemal et al, 1972). The majority of ESCCs are diagnosed at advanced stages and the overall 5-year survival rate is relatively poor, while the 5-year survival rate for early stage diagnosed ESCC patients is significantly higher (Besharat et al, 2008). It is imperative to identify biomarkers for early diagnosis of ESCC patients
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
