Abstract
The risk of developing metachronous gastric cancer (MGC) following curative endoscopic submucosal dissection (ESD) of early gastric cancer (EGC) remains even after eradicating Helicobacter pylori (HP) successfully. We screened initial EGC and adjacent non-cancerous mucosa ESD-resected specimens for somatic variants of 409 cancer-related genes, assessing their mutational burden (MB) to predict molecular markers for metachronous post-ESD development. We compared variants between ten patients diagnosed with MGC more than 3 years after ESD and ten age-matched patients who did not have MGC developments after successful HP eradication. We found no significant background differences between the two groups. In adjacent non-cancerous mucosa, the MB tended to be higher in the patients with metachronous developments than in the others. Somatic genomic alterations of RECQL4, JAK3, ARID1A, and MAGI1 genes were significantly associated with MGC development. The criteria including both the MB and their variants, which had potential significant values for predicting MGC. In conclusion, combined of assessing specific somatic variants and MB may be useful for predicting MGC development. This study included a limited number of subjects; however, our novel findings may encourage further exploration of the significance of the molecular features of EGC that predict MGC development, thereby promoting focused follow-up strategies and helping elucidate the mechanisms.
Highlights
The risk of developing metachronous gastric cancer (MGC) following curative endoscopic submucosal dissection (ESD) of early gastric cancer (EGC) remains even after eradicating Helicobacter pylori (HP) successfully
Our results suggested that alterations of specific somatic variants and mutational burden may be linked to the risk of MGC development
We found no significant differences between the non-MGC development (N) group and the metachronous development (M) group in terms of men/women ratios, alcohol consumption, current smoker rates, tumor locations, macroscopic types, gastric mucosal atrophy degrees, the presence of intestinal metaplasia, and age, body mass index, or maximum size of tumor means
Summary
The risk of developing metachronous gastric cancer (MGC) following curative endoscopic submucosal dissection (ESD) of early gastric cancer (EGC) remains even after eradicating Helicobacter pylori (HP) successfully. Somatic genomic alterations of RECQL4, JAK3, ARID1A, and MAGI1 genes were significantly associated with MGC development The criteria including both the MB and their variants, which had potential significant values for predicting MGC. The non-cancerous gastric mucosa’s methylation level in gastric cancer (GC) patients, especially in the tumor-suppressor miR124a-3, was significantly associated with an increased risk of developing MGC by a multicenter, prospective cohort study[12,13] These findings suggest that altering the normal gastric mucosa or initial EGCs may be markers for MGC occurrence. The further analysis of these alterations, using a large number of patients, may help to estimate the risk of MGC and elucidate the mechanisms
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