Comprehensive genetic analysis of poorly differentiated gastric cancer in young females

IF 3.3 4区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Annals of Gastroenterological Surgery Pub Date : 2025-04-29 DOI:10.1002/ags3.70020

Nobuhiro Nakazawa, Takehiko Yokobori, Yohei Morishita, Akinobu Echigo, Reika Kawabata-Iwakawa, Akiharu Kimura, Akihiko Sano, Makoto Sakai, Ken Shirabe, Hiroshi Saeki

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Abstract

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.

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年轻女性低分化胃癌的综合遗传分析

目的年轻女性低分化胃癌高发的原因尚不清楚。因此，本研究旨在对年轻女性低分化胃癌高发的相关因素进行全面的遗传学分析。方法对2015年4月至2020年12月在群马大学医院接受胃癌手术的299例患者进行分析。其中，我们选取年龄30-50岁的女性低分化胃癌、女性分化胃癌和男性低分化胃癌病例。每种情况下发现三个符合条件的病例并纳入研究。从解剖的福尔马林固定石蜡包埋的组织样本中分离RNA，然后进行RNA测序。利用独创性通路分析方法对结果进行分析，以阐明年轻女性低分化胃癌高发的机制。结果地塞米松、β-雌二醇和白细胞介素-1β是年轻女性低分化胃癌的重要上游调控因子。β-雌二醇的下游靶基因包括雄性生殖细胞相关激酶、生长分化因子6、内皮素2和XI型胶原α 1链。结论我们详细的RNA-seq分析显示，女性性激素β-雌二醇在年轻女性低分化胃癌的发展中起作用。

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