鉴定与胃癌预后和转移相关的新型基因特征

IF 6.6 2区 医学 Q1 Medicine
Cellular Oncology Pub Date : 2024-08-01 Epub Date: 2024-03-13 DOI:10.1007/s13402-024-00932-y
Joseba Elizazu, Aizpea Artetxe-Zurutuza, Maddalen Otaegi-Ugartemendia, Veronica Moncho-Amor, Manuel Moreno-Valladares, Ander Matheu, Estefania Carrasco-Garcia
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引用次数: 0

摘要

背景:胃癌(GC)的预后较差,这是早期复发和转移率高的结果。复发或转移性胃癌患者的中位预期寿命仅为 8 个月。人们对 GC 进展的机制仍知之甚少:我们利用 TCGA 的 GEPIA 公开 GC 数据集,在与总生存期(OS)和无病生存期(DFS)最显著相关的 100 个基因中确定了匹配基因。结果在 ACRG 队列中得到了证实,并在使用我们自己的分析管道从多个队列中整合获得的 2000 多个 GC 病例中得到了证实。Kaplan-Meier方法和多变量Cox回归分析用于确定预后意义,线性建模和相关性分析用于确定与临床病理参数和生物学特征的关联。在GC细胞中对候选基因进行了体外和体内功能研究,并通过RNA测序研究了相关的分子通路:结果:ANKRD6、ITIH3、SORCS3、NPY1R和CCDC178单独或作为特征基因的高表达与GC的不良预后和疾病复发有关。此外,ANKRD6和ITIH3在转移中的表达量明显较高,其水平与上皮到间质转化(EMT)和干性标志物相关。与此相一致,RNAseq分析揭示了参与EMT的基因在ANKRD6沉默细胞中的不同表达。最后,GC转移细胞中的ANKRD6沉默显示了GC体外和体内致瘤和转移特性的减弱:我们的研究发现了一种参与 GC 恶性肿瘤和预后的新型特征,并揭示了 ANKRD6 在 GC 中的新型促转移作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Identification of a novel gene signature related to prognosis and metastasis in gastric cancer.

Identification of a novel gene signature related to prognosis and metastasis in gastric cancer.

Background: Gastric Cancer (GC) presents poor outcome, which is consequence of the high incidence of recurrence and metastasis at early stages. GC patients presenting recurrent or metastatic disease display a median life expectancy of only 8 months. The mechanisms underlying GC progression remain poorly understood.

Methods: We took advantage of public available GC datasets from TCGA using GEPIA, and identified the matched genes among the 100 genes most significantly associated with overall survival (OS) and disease free survival (DFS). Results were confirmed in ACRG cohort and in over 2000 GC cases obtained from several cohorts integrated using our own analysis pipeline. The Kaplan-Meier method and multivariate Cox regression analyses were used for prognostic significance and linear modelling and correlation analyses for association with clinic-pathological parameters and biological hallmarks. In vitro and in vivo functional studies were performed in GC cells with candidate genes and the related molecular pathways were studied by RNA sequencing.

Results: High expression of ANKRD6, ITIH3, SORCS3, NPY1R and CCDC178 individually and as a signature was associated with poor prognosis and recurrent disease in GC. Moreover, the expression of ANKRD6 and ITIH3 was significantly higher in metastasis and their levels associated to Epithelial to Mesenchymal Transition (EMT) and stemness markers. In line with this, RNAseq analysis revealed genes involved in EMT differentially expressed in ANKRD6 silencing cells. Finally, ANKRD6 silencing in GC metastatic cells showed impairment in GC tumorigenic and metastatic traits in vitro and in vivo.

Conclusions: Our study identified a novel signature involved in GC malignancy and prognosis, and revealed a novel pro-metastatic role of ANKRD6 in GC.

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来源期刊
Cellular Oncology
Cellular Oncology Biochemistry, Genetics and Molecular Biology-Cancer Research
CiteScore
10.40
自引率
1.50%
发文量
0
审稿时长
16 weeks
期刊介绍: The Official Journal of the International Society for Cellular Oncology Focuses on translational research Addresses the conversion of cell biology to clinical applications Cellular Oncology publishes scientific contributions from various biomedical and clinical disciplines involved in basic and translational cancer research on the cell and tissue level, technical and bioinformatics developments in this area, and clinical applications. This includes a variety of fields like genome technology, micro-arrays and other high-throughput techniques, genomic instability, SNP, DNA methylation, signaling pathways, DNA organization, (sub)microscopic imaging, proteomics, bioinformatics, functional effects of genomics, drug design and development, molecular diagnostics and targeted cancer therapies, genotype-phenotype interactions. A major goal is to translate the latest developments in these fields from the research laboratory into routine patient management. To this end Cellular Oncology forms a platform of scientific information exchange between molecular biologists and geneticists, technical developers, pathologists, (medical) oncologists and other clinicians involved in the management of cancer patients. In vitro studies are preferentially supported by validations in tumor tissue with clinicopathological associations.
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