Abstract
Background: Prognosis of esophageal squamous cell carcinoma (ESCC) patients remains poor, and the chemoradiotherapy (CRT) applied to ESCC patients often failed. Therefore, development of biomarkers to predict CRT response is immensely important for choosing the best treatment strategy of an individual patient. Methods: The methylation array and pyrosequencing methylation assay were performed in pre-treatment endoscopic biopsies to identify probes with differential CpG methylation levels between good and poor CRT responders in a cohort of 12 ESCC patients. Receiver operating characteristic curves and multivariate logistic regressions were conducted to build the risk score equation of selected CpG probes in another cohort of 91 ESCC patients to predict CRT response. Kaplan–Meier analysis was used to estimate progression-free survival or time-to-progression of patients predicted with good and poor CRT responses. Results: Nine differentially methylated CpG probes were identified to be associated with CRT response. A risk score equation comprising six CpG probes located in IFNGR2, KCNK4, NOTCH4, NPY, PAX6, and SOX17 genes were built. The risk score was derived from the sum of each probe multiplied by its corresponding coefficient. Such a risk score has a good prediction performance in discriminating poor CRT responders from good responders (AUC: 0.930). Moreover, poor CRT responders predicted by risk score significantly had poorer prognosis in terms of shorter progression-free survival and time-to-progression (p = 0.004–0.008). Conclusion: We established a proof-of-concept CRT response prediction panel consisting of six-CpG methylation biomarkers in identifying ESCC patients who are at high risk of CRT failure and need intensive care.
| Original language | English |
|---|---|
| Pages (from-to) | 705-714 |
| Number of pages | 10 |
| Journal | Journal of Gastroenterology |
| Volume | 52 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 2017 Jun 1 |
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All Science Journal Classification (ASJC) codes
- Gastroenterology
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A six-CpG panel with DNA methylation biomarkers predicting treatment response of chemoradiation in esophageal squamous cell carcinoma. / Chang, Wei Lun; Lai, Wu Wei; Kuo, I. Ying; Lin, Chien Yu; Lu, Pei Jung; Sheu, Bor Shyang; Wang, Yi Ching.
In: Journal of Gastroenterology, Vol. 52, No. 6, 01.06.2017, p. 705-714.Research output: Contribution to journal › Article
TY - JOUR
T1 - A six-CpG panel with DNA methylation biomarkers predicting treatment response of chemoradiation in esophageal squamous cell carcinoma
AU - Chang, Wei Lun
AU - Lai, Wu Wei
AU - Kuo, I. Ying
AU - Lin, Chien Yu
AU - Lu, Pei Jung
AU - Sheu, Bor Shyang
AU - Wang, Yi Ching
PY - 2017/6/1
Y1 - 2017/6/1
N2 - Background: Prognosis of esophageal squamous cell carcinoma (ESCC) patients remains poor, and the chemoradiotherapy (CRT) applied to ESCC patients often failed. Therefore, development of biomarkers to predict CRT response is immensely important for choosing the best treatment strategy of an individual patient. Methods: The methylation array and pyrosequencing methylation assay were performed in pre-treatment endoscopic biopsies to identify probes with differential CpG methylation levels between good and poor CRT responders in a cohort of 12 ESCC patients. Receiver operating characteristic curves and multivariate logistic regressions were conducted to build the risk score equation of selected CpG probes in another cohort of 91 ESCC patients to predict CRT response. Kaplan–Meier analysis was used to estimate progression-free survival or time-to-progression of patients predicted with good and poor CRT responses. Results: Nine differentially methylated CpG probes were identified to be associated with CRT response. A risk score equation comprising six CpG probes located in IFNGR2, KCNK4, NOTCH4, NPY, PAX6, and SOX17 genes were built. The risk score was derived from the sum of each probe multiplied by its corresponding coefficient. Such a risk score has a good prediction performance in discriminating poor CRT responders from good responders (AUC: 0.930). Moreover, poor CRT responders predicted by risk score significantly had poorer prognosis in terms of shorter progression-free survival and time-to-progression (p = 0.004–0.008). Conclusion: We established a proof-of-concept CRT response prediction panel consisting of six-CpG methylation biomarkers in identifying ESCC patients who are at high risk of CRT failure and need intensive care.
AB - Background: Prognosis of esophageal squamous cell carcinoma (ESCC) patients remains poor, and the chemoradiotherapy (CRT) applied to ESCC patients often failed. Therefore, development of biomarkers to predict CRT response is immensely important for choosing the best treatment strategy of an individual patient. Methods: The methylation array and pyrosequencing methylation assay were performed in pre-treatment endoscopic biopsies to identify probes with differential CpG methylation levels between good and poor CRT responders in a cohort of 12 ESCC patients. Receiver operating characteristic curves and multivariate logistic regressions were conducted to build the risk score equation of selected CpG probes in another cohort of 91 ESCC patients to predict CRT response. Kaplan–Meier analysis was used to estimate progression-free survival or time-to-progression of patients predicted with good and poor CRT responses. Results: Nine differentially methylated CpG probes were identified to be associated with CRT response. A risk score equation comprising six CpG probes located in IFNGR2, KCNK4, NOTCH4, NPY, PAX6, and SOX17 genes were built. The risk score was derived from the sum of each probe multiplied by its corresponding coefficient. Such a risk score has a good prediction performance in discriminating poor CRT responders from good responders (AUC: 0.930). Moreover, poor CRT responders predicted by risk score significantly had poorer prognosis in terms of shorter progression-free survival and time-to-progression (p = 0.004–0.008). Conclusion: We established a proof-of-concept CRT response prediction panel consisting of six-CpG methylation biomarkers in identifying ESCC patients who are at high risk of CRT failure and need intensive care.
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U2 - 10.1007/s00535-016-1265-2
DO - 10.1007/s00535-016-1265-2
M3 - Article
C2 - 27671002
AN - SCOPUS:84991394310
VL - 52
SP - 705
EP - 714
JO - Journal of Gastroenterology
JF - Journal of Gastroenterology
SN - 0944-1174
IS - 6
ER -