ETS Family Transcription Factors in Gastric Cancer and the Role of ELF3 in the Core Metaplasia Transcription Factor Network.

[BACKGROUND] E26 transformation-specific (ETS) family transcription factors have confirmed roles in several types of cancers. This study aimed to clarify the role of ETS family transcription factor alterations in gastric cancers.

[METHODS] This study examines molecular alterations of ETS transcription factors in gastric adenocarcinomas based on an analysis of publicly available cohorts from the Protein Atlas and the Cancer Genome Atlas. The expression and relationships of members of the ETS transcription factor family with other important factors in the process of gastric carcinogenesis were evaluated using the same resources.

[RESULTS] mRNA expression levels of ETS family members in gastric carcinoma tissues were variable, with ELF3, ETS2, EHF, ERF, and ELF1 being the family members with the highest expression. Mutations in individual transcription factors of the ETS family were rare in gastric cancers. The family member ELF3 was well expressed in the mRNA level in a subset of gastric cancers (n = 91), and its expression correlated with the expression of other transcription factors involved in gastric cancer pathogenesis, including HNF4A, HNF1A, CDX2, GATA4, GATA6, and EHF. Cancers with high co-expression of ELF3 and HNF4A were frequently chromosomally instability (CIN), intestinal-type adenocarcinomas, and harbored mutations and deletions.

[CONCLUSION] Expression of E74 like ETS transcription factor 3 (ELF3), an ETS transcription family member, correlates with expression of other key factors in gastric cancer and confers specific characteristics that may become exploited in targeted therapeutic interventions.