Meta‐analysis of the prognostic value of CpG island methylator phenotype in gastric cancer

Background CpG island methylator phenotype (CIMP) has been identified as a distinct molecular subtype of gastric cancer, yet associations with survival are conflicting. A meta‐analysis was performed to estimate the prognostic significance of CIMP. Methods Embase, MEDLINE, PubMed, PubMed Central and Cochrane databases were searched systematically for studies related to the association between CIMP and survival in patients undergoing potentially curative resection for gastric cancer. Results A total of 918 patients from ten studies were included, and the median proportion of tumours with CIMP‐high (CIMP‐H) status was 40·9 (range 4·8–63) per cent. Gene panels for assessing CIMP status varied between the studies. Pooled analysis suggested that specimens exhibiting CIMP‐H were associated with poorer 5‐year survival (odds ratio (OR) for death 1·48, 95 per cent c.i. 1·10 to 1·99; P = 0·009). Significant heterogeneity was observed between studies (I2 = 88 per cent, P < 0·001). Subgroup analysis according to whether studies showed a tendency towards poor (5 studies) or improved (5) outcomes for patients with CIMP‐H tumours, revealed that CIMP‐H was associated with both poor (OR for death 8·15, 4·65 to 14·28, P < 0·001; heterogeneity I2 = 52 per cent, P = 0·08) and improved (OR 0·42, 0·27 to 0·65; P < 0·001, heterogeneity I2 = 0 per cent, P = 0·960) survival. Conclusion There was heterogeneity in the gene panels used to identify CIMP, which may explain the survival differences. Heterogeneity in gene panels used