The differences in biological behavior and gene expression characteristics between pure and mixed early gastric signet ring cell carcinomas

Background: The biological behavior of signet ring cell carcinoma (SRCC) in early gastric cancer (EGC) is not well understood.Aims: We aimed to investigate the clinicopathologic and prognostic differences, and explore differences in the gene expression characteristics between pure early SRCC and mixed early SRCC. Methods: We retrospectively analyzed 1707 EGC patients. We also conducted a meta-analysis to com-pare biological behavior in pure SRCC and mixed SRCC. We explored gene expression levels of N6-methyadenosine (m6A) regulators in pure SRCC and mixed SRCC. Results: Compared with pure SRCC, mixed SRCC was associated with an increased risk of submucosal invasion, perineural invasion, LVI and LNM. LNM was more common in mixed SRCC than with pure SRCC who met the indications for endoscopic submucosal dissection (ESD) (16.67% vs 2.78%). There was no difference in the overall survival between pure SRCC and mixed SRCC in EGCs ( P = 0.10). Expression of m6A regulators WTAP, FTO and VIRMA was significantly higher in mixed SRCC than that in pure SRCC ( P < 0.05).Conclusion: Mixed SRCC displayed more aggressive biological behavior than pure SRCC in EGC. WTAP, FTO and VIRMA were expressed at significantly different levels in the two types of EGC, and may have important roles in the observed differences in biological behavior.(c) 2022 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.