Comprehensive genetic analysis of poorly differentiated gastric cancer in young females.

AIM

The reasons behind the high prevalence of poorly differentiated gastric cancer in young females remain unclear. Therefore, this study aimed to conduct a comprehensive genetic analysis to investigate the factors responsible for the high prevalence of poorly differentiated gastric cancer in young females.

METHODS

We analyzed 299 patients who underwent gastric cancer surgery at the Gunma University Hospital between April 2015 and December 2020. Among them, we selected cases of poorly differentiated gastric cancer in females, differentiated gastric cancer in females, and poorly differentiated gastric cancer in males, aged 30-50 years. Three eligible cases of each condition were found and included in the study. RNA was isolated from dissected formalin-fixed, paraffin-embedded tissue samples, followed by RNA sequencing. The results were analyzed using ingenuity pathway analysis to elucidate the mechanisms contributing to the high incidence of poorly differentiated gastric cancer in young females.

RESULTS

Dexamethasone, β-estradiol, and interleukin-1β were identified as significant upstream regulators associated with poorly differentiated gastric cancer in young females. The downstream target genes of β-estradiol included male germ cell-associated kinase, growth differentiation factor 6, endothelin 2, and collagen type XI alpha 1 chain.

CONCLUSION

Our detailed RNA-seq analysis revealed that the female sex hormone, β-estradiol, plays a role in the development of poorly differentiated gastric cancer in young females.