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Methylated DNA markers predict gastric cancer
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HONOLULU — New research presented in a plenary session at ACG 2015 showed that multiple methylated DNA markers accurately predicted gastric cancer among U.S. and Korean cohorts.
“In this study, we identified novel methylated DNA markers by whole methylome sequencing and then validated best candidates in tissues from patient cohorts in the U.S. and South Korea,” Bradley W. Anderson, MD, Mayo Clinic, Rochester, Minnesota, said during his presentation.
Seventeen methylated DNA marker candidates from 35 patients from the U.S. and 50 from Korea with intact adenocarcinoma were evaluated by Anderson and colleagues and compared them with controls. The U.S. cohort was compared with 65 healthy controls with normal gastric epithelia. The 50 Korean gastric patients were treated at Seoul University Hospital, South Korea, and served as their own controls. Adjacent normal mucosa was sampled at the time of endoscopic intervention for the Korean gastric cancer cases, according to Anderson.
For each marker, area under the curve (AUC) was calculated using nominal logistic regression. The DNA from microdissected tissues was assayed via methylation-specific polymerase chain reaction and marker levels were standardized to template DNA or assayed beta-actin, according to the research.
The researchers found the top 10 DNA markers included ARHGEF4, ELMO1, ABCB1, CLEC11A, ST8SIA1, SFMBT2, CD1D, CYP26C1, ZNF569 and C13ORF18.
A panel of the 10 markers detected gastric cancer in 100% of the U.S. cohort and 94% of the South Korean cohort, with a specificity of 95%.
The AUCs in the U.S. cohort were 0.92 for ARHGEF4; 0.91 for ELMO1; 0.89 for ABCB1; 0.88 for CLEC11A; 0.85 for ST8SIA1; 0.82 for SFMBT2; 0.82 for CD1D; 0.81 for CYP26C1; 0.75 for ZNF569; and 0.66 for C13ORF18.
Among the South Korean patients, AUCs were 0.73 for ARHGEF4; 0.9 for ELMO1; 0.78 for ABCB1; 0.75 for CLEC11A; 0.8 for ST8SIA1; 0.94 for SFMBT2; 0.87 for CD1D; 0.79 for CYP26C1; 0.75 for ZNF569; and 0.79 for C13ORF18.
“[The biomarkers] had high accuracy and some markers were similarly discriminant between cohorts,” Anderson said.
Specific markers, such as ELMO1, showed “high discrimination” for gastric cancer in both patient cohorts. However, other markers, including ARHGEF4, had more varied discrimination due to high background on normal controls across patient cohorts.
“A panel of informative methylated DNA markers were identified with high sensitivity and specificity for [gastric cancer] in both U.S. and South Korean patients,” Anderson concluded. “Further exploration of these candidate methylated DNA markers for application in early [gastric cancer] detection is warranted.” – by Melinda Stevens
Reference:
Anderson BW, et al. Abstract 16. Presented at: ACG; Oct. 16-21, 2015; Honolulu.
Disclosures: The researchers report no relevant financial disclosures.