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年轻女性低分化胃癌的综合基因分析

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

作者信息

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

机构信息

Department of General Surgical Science Gunma University Graduate School of Medicine Maebashi Gunma Japan.

Division of Integrated Oncology Research Gunma University, Initiative for Advanced Research (GIAR) Maebashi Gunma Japan.

出版信息

Ann Gastroenterol Surg. 2025 Apr 29;9(5):926-932. doi: 10.1002/ags3.70020. eCollection 2025 Sep.

DOI:10.1002/ags3.70020
PMID:40922916
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12414586/
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.

摘要

目的

年轻女性中低分化胃癌高发的原因尚不清楚。因此，本研究旨在进行全面的基因分析，以探究导致年轻女性低分化胃癌高发的因素。

方法

我们分析了2015年4月至2020年12月期间在群马大学医院接受胃癌手术的299例患者。其中，我们选取了年龄在30至50岁之间的女性低分化胃癌病例、女性高分化胃癌病例以及男性低分化胃癌病例。每种情况各找到3例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组织样本中分离RNA，随后进行RNA测序。使用 Ingenuity Pathway Analysis 对结果进行分析，以阐明导致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被确定为与年轻女性低分化胃癌相关的重要上游调节因子。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α1链。

结论

我们详细的RNA测序分析表明，女性性激素β-雌二醇在年轻女性低分化胃癌的发生发展中起作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38fa/12414586/c04582fa8bd9/AGS3-9-926-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38fa/12414586/ddfc123520ea/AGS3-9-926-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38fa/12414586/c04582fa8bd9/AGS3-9-926-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38fa/12414586/ddfc123520ea/AGS3-9-926-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38fa/12414586/c04582fa8bd9/AGS3-9-926-g001.jpg

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