TGFβ 信号通路影响局部晚期结直肠癌的脑转移特征

IF 4.2 3区 医学 Q2 ONCOLOGY
Sven Jacob, Ilja Balonov, Vindi Jurinovic, Christian Heiliger, Tengis Tschaidse, Jörg Kumbrink, Thomas Kirchner, Jens Werner, Martin K. Angele, Marlies Michl, Jens Neumann
{"title":"TGFβ 信号通路影响局部晚期结直肠癌的脑转移特征","authors":"Sven Jacob, Ilja Balonov, Vindi Jurinovic, Christian Heiliger, Tengis Tschaidse, Jörg Kumbrink, Thomas Kirchner, Jens Werner, Martin K. Angele, Marlies Michl, Jens Neumann","doi":"10.1007/s10585-024-10277-3","DOIUrl":null,"url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Rationale</h3><p>Colorectal Cancer (CRC) represents the third most common type of cancer in Germany and the second most common cancer-related cause of death worldwide. Distant metastases are still the main limit for patient survival. While liver metastases as well as peritoneal carcinomatosis can often either be resected or treated with systemic therapy, little options remain for brain metastases. Additionally, a number of studies has already investigated hepatic, peritoneal, pulmonary as well as continuing distant metastases in colorectal cancer. Yet, with respect to tumor biology and brain metastases, little is known so far.</p><h3 data-test=\"abstract-sub-heading\">Material and methods</h3><p>Two cohorts, M0 without distant spread and BRA with brain metastases were build. RNA was isolated from paraffin embedded specimen. Gene expression was performed by an RNA NanoString-Analysis using the nCounter® PanCancer Progression Panel by NanoString-Technologies (Hamburg, Germany). Results were analysed by principal component analysis, gene expression and pathway analysis using commonly available databases such as KEGG as benchmark for comparison.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>We were able to determine a gene signature that provides a sophisticated group separation between M0 and BRA using principal component analysis. All genes with strong loading characteristics on principal component 1 were cross-referenced with the subsequently performed accurate gene set enrichment analysis (GSEA). The GSEA revealed a clear dysregulation of the TGFβ pathway in compared cohorts M0 and BRA. Interestingly, the targeted pathways analysis of the identified genes confirmed that in fact almost all strong loading genes of PC1 play a role in the TGFβ pathway.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Our results suggest the TGFβ pathway as a crucial player in the development of brain metastases in primary CRC. In some types of colorectal cancer, downregulation of the TGFβ pathway might hinder primary colorectal cancer to metastasize to the nervous system. While the paradoxical functioning of the TGFβ pathway is still not fully understood, these shed light on yet another clinical implication of this complex pathway.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":null,"pages":null},"PeriodicalIF":4.2000,"publicationDate":"2024-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"TGFβ signalling pathway impacts brain metastases profiles in locally advanced colorectal cancer\",\"authors\":\"Sven Jacob, Ilja Balonov, Vindi Jurinovic, Christian Heiliger, Tengis Tschaidse, Jörg Kumbrink, Thomas Kirchner, Jens Werner, Martin K. Angele, Marlies Michl, Jens Neumann\",\"doi\":\"10.1007/s10585-024-10277-3\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<h3 data-test=\\\"abstract-sub-heading\\\">Rationale</h3><p>Colorectal Cancer (CRC) represents the third most common type of cancer in Germany and the second most common cancer-related cause of death worldwide. Distant metastases are still the main limit for patient survival. While liver metastases as well as peritoneal carcinomatosis can often either be resected or treated with systemic therapy, little options remain for brain metastases. Additionally, a number of studies has already investigated hepatic, peritoneal, pulmonary as well as continuing distant metastases in colorectal cancer. Yet, with respect to tumor biology and brain metastases, little is known so far.</p><h3 data-test=\\\"abstract-sub-heading\\\">Material and methods</h3><p>Two cohorts, M0 without distant spread and BRA with brain metastases were build. RNA was isolated from paraffin embedded specimen. Gene expression was performed by an RNA NanoString-Analysis using the nCounter® PanCancer Progression Panel by NanoString-Technologies (Hamburg, Germany). Results were analysed by principal component analysis, gene expression and pathway analysis using commonly available databases such as KEGG as benchmark for comparison.</p><h3 data-test=\\\"abstract-sub-heading\\\">Results</h3><p>We were able to determine a gene signature that provides a sophisticated group separation between M0 and BRA using principal component analysis. All genes with strong loading characteristics on principal component 1 were cross-referenced with the subsequently performed accurate gene set enrichment analysis (GSEA). The GSEA revealed a clear dysregulation of the TGFβ pathway in compared cohorts M0 and BRA. Interestingly, the targeted pathways analysis of the identified genes confirmed that in fact almost all strong loading genes of PC1 play a role in the TGFβ pathway.</p><h3 data-test=\\\"abstract-sub-heading\\\">Conclusion</h3><p>Our results suggest the TGFβ pathway as a crucial player in the development of brain metastases in primary CRC. In some types of colorectal cancer, downregulation of the TGFβ pathway might hinder primary colorectal cancer to metastasize to the nervous system. While the paradoxical functioning of the TGFβ pathway is still not fully understood, these shed light on yet another clinical implication of this complex pathway.</p>\",\"PeriodicalId\":10267,\"journal\":{\"name\":\"Clinical & Experimental Metastasis\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.2000,\"publicationDate\":\"2024-03-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical & Experimental Metastasis\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s10585-024-10277-3\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical & Experimental Metastasis","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10585-024-10277-3","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

理论依据在德国,直肠癌(CRC)是第三大常见癌症类型,也是全球第二大最常见的癌症相关死因。远处转移仍然是限制患者生存的主要因素。虽然肝转移和腹膜癌通常可以切除或采用全身治疗,但对于脑转移却没有什么办法。此外,许多研究已经对结直肠癌的肝转移、腹膜转移、肺转移以及持续性远处转移进行了调查。材料和方法建立了两个队列:无远处转移的 M0 和有脑转移的 BRA。从石蜡包埋标本中分离出 RNA。基因表达采用 NanoString-Technologies 公司(德国汉堡)的 nCounter® PanCancer Progression Panel 进行 RNA NanoString 分析。通过主成分分析、基因表达和通路分析对结果进行了分析,并将常用数据库(如 KEGG)作为比较基准。所有在主成分 1 上具有较强负载特征的基因都与随后进行的精确基因组富集分析(GSEA)进行了交叉比对。GSEA显示,在M0和BRA的比较组中,TGFβ通路明显失调。有趣的是,对鉴定出的基因进行的靶向通路分析证实,事实上 PC1 的几乎所有强负荷基因都在 TGFβ 通路中发挥作用。在某些类型的结直肠癌中,TGFβ通路的下调可能会阻碍原发性结直肠癌向神经系统转移。尽管人们对 TGFβ 通路的自相矛盾的功能仍不完全了解,但这些研究揭示了这一复杂通路的另一个临床意义。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

TGFβ signalling pathway impacts brain metastases profiles in locally advanced colorectal cancer

TGFβ signalling pathway impacts brain metastases profiles in locally advanced colorectal cancer

Rationale

Colorectal Cancer (CRC) represents the third most common type of cancer in Germany and the second most common cancer-related cause of death worldwide. Distant metastases are still the main limit for patient survival. While liver metastases as well as peritoneal carcinomatosis can often either be resected or treated with systemic therapy, little options remain for brain metastases. Additionally, a number of studies has already investigated hepatic, peritoneal, pulmonary as well as continuing distant metastases in colorectal cancer. Yet, with respect to tumor biology and brain metastases, little is known so far.

Material and methods

Two cohorts, M0 without distant spread and BRA with brain metastases were build. RNA was isolated from paraffin embedded specimen. Gene expression was performed by an RNA NanoString-Analysis using the nCounter® PanCancer Progression Panel by NanoString-Technologies (Hamburg, Germany). Results were analysed by principal component analysis, gene expression and pathway analysis using commonly available databases such as KEGG as benchmark for comparison.

Results

We were able to determine a gene signature that provides a sophisticated group separation between M0 and BRA using principal component analysis. All genes with strong loading characteristics on principal component 1 were cross-referenced with the subsequently performed accurate gene set enrichment analysis (GSEA). The GSEA revealed a clear dysregulation of the TGFβ pathway in compared cohorts M0 and BRA. Interestingly, the targeted pathways analysis of the identified genes confirmed that in fact almost all strong loading genes of PC1 play a role in the TGFβ pathway.

Conclusion

Our results suggest the TGFβ pathway as a crucial player in the development of brain metastases in primary CRC. In some types of colorectal cancer, downregulation of the TGFβ pathway might hinder primary colorectal cancer to metastasize to the nervous system. While the paradoxical functioning of the TGFβ pathway is still not fully understood, these shed light on yet another clinical implication of this complex pathway.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
CiteScore
7.80
自引率
5.00%
发文量
55
审稿时长
12 months
期刊介绍: The Journal''s scope encompasses all aspects of metastasis research, whether laboratory-based, experimental or clinical and therapeutic. It covers such areas as molecular biology, pharmacology, tumor biology, and clinical cancer treatment (with all its subdivisions of surgery, chemotherapy and radio-therapy as well as pathology and epidemiology) insofar as these disciplines are concerned with the Journal''s core subject of metastasis formation, prevention and treatment.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信