Representing ECM composition and EMT pathways in gastric cancer using a new metastatic gene signature.

IF 4.6 2区生物学 Q2 CELL BIOLOGY Frontiers in Cell and Developmental Biology Pub Date : 2024-11-05 eCollection Date: 2024-01-01 DOI:10.3389/fcell.2024.1481818

Francesco Albano, Sabino Russi, Simona Laurino, Pellegrino Mazzone, Giuseppina Di Paola, Pietro Zoppoli, Elena Amendola, Chiara Balzamo, Ottavia Bartolo, Mario Ciuffi, Orazio Ignomirelli, Alessandro Sgambato, Rocco Galasso, Mario De Felice, Geppino Falco, Giovanni Calice

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Abstract

Introduction: Gastric cancer (GC) is an aggressive and heterogeneous malignancy marked by cellular and molecular diversity. In GC, cancer cells invade locally in the stomach at stage I and can progress to metastasis in distant organs by stage IV, where it often becomes fatal.

Methods: We analyzed gene expression profiles from 719 stage I and stage IV GC patients across seven public datasets, conducting functional enrichment analysis to identify a gene signature linked to disease progression. Additionally, we developed an in vitro model of a simplified extracellular matrix (ECM) for cell-based assays.

Results: Our analysis identified a progression-associated gene signature (APOD, COL1A2, FSTL1, GEM, LUM, and SPARC) that characterizes stage IV GC. This signature is associated with ECM organization and epithelial-to-mesenchymal transition (EMT), both of which influence the tumor microenvironment by promoting cell invasion and triggering EMT.

Discussion: This gene signature may help identify stage I GC patients at higher risk, offering potential utility in early-stage patient management. Furthermore, our experimental ECM model may serve as a platform for investigating molecular mechanisms underlying metastatic spread in gastric cancer.

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利用新的转移基因特征表示胃癌中的 ECM 组成和 EMT 通路。

简介胃癌（GC）是一种侵袭性和异质性恶性肿瘤，具有细胞和分子多样性。在 GC 中，癌细胞在 I 期时从胃部局部侵入，到 IV 期时可发展到远处器官转移，并往往致命：我们分析了 719 例 I 期和 IV 期 GC 患者在 7 个公开数据集中的基因表达谱，并进行了功能富集分析，以确定与疾病进展相关的基因特征。此外，我们还开发了一个简化细胞外基质（ECM）的体外模型，用于基于细胞的检测：结果：我们的分析确定了一个与疾病进展相关的基因特征（APOD、COL1A2、FSTL1、GEM、LUM 和 SPARC），它是 IV 期 GC 的特征。该特征与 ECM 组织和上皮细胞向间质转化（EMT）有关，两者都会通过促进细胞侵袭和引发 EMT 来影响肿瘤微环境：该基因特征可能有助于识别风险较高的 I 期 GC 患者，为早期患者管理提供了潜在的实用性。此外，我们的 ECM 实验模型可作为研究胃癌转移扩散分子机制的平台。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Frontiers in Cell and Developmental Biology Biochemistry, Genetics and Molecular Biology-Cell Biology

CiteScore

9.70

自引率

3.60%

发文量

2531

审稿时长

12 weeks

期刊介绍： Frontiers in Cell and Developmental Biology is a broad-scope, interdisciplinary open-access journal, focusing on the fundamental processes of life, led by Prof Amanda Fisher and supported by a geographically diverse, high-quality editorial board. The journal welcomes submissions on a wide spectrum of cell and developmental biology, covering intracellular and extracellular dynamics, with sections focusing on signaling, adhesion, migration, cell death and survival and membrane trafficking. Additionally, the journal offers sections dedicated to the cutting edge of fundamental and translational research in molecular medicine and stem cell biology. With a collaborative, rigorous and transparent peer-review, the journal produces the highest scientific quality in both fundamental and applied research, and advanced article level metrics measure the real-time impact and influence of each publication.