Related Experiment Video
Updated: Jan 9, 2026
Molecular Profiling of the Invasive Tumor Microenvironment in a 3-Dimensional Model of Colorectal Cancer Cells and Ex vivo Fibroblasts
Published on: April 29, 2014
Subtype-specific RNA sequencing using micro-dissection revealed extracellular matrix alterations as key factors in
Chongze Yuan1,2,3, Xiao Chen1,2,3, Yizhou Peng1,2,3
1Departments of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, Shanghai, China.
Background:
Tumor invasion is a critical step in tumorigenesis and represents an important therapeutic target. However, the molecular mechanisms underlying the invasion process of lung adenocarcinoma (LUAD) remain poorly understood. In this study, we investigated the transcriptomic and epigenetic alterations occurring during LUAD invasion to elucidate the key biological processes.
Methods:
Frozen section of LUAD tumors, which contained both invasive and non-invasive subtypes, was selected as the study model. These subtypes were identified, micro-dissected, and separately processed for RNA sequencing (RNA-seq). Subsequent analysis identified differentially expressed genes (DEGs) and significantly enriched biological processes. Additionally, RNA-seq data from independent LUAD tissues were analyzed to screen for critical genes, and H3K27ac chromatin immunoprecipitation sequencing (ChIP-seq) was conducted to explore potential regulatory mechanisms. Finally, survival analysis was performed using The Cancer Genome Atlas (TCGA) database to validate the clinical relevance of the identified genes.
Results:
Subtype-specific RNA-seq analysis revealed that alteration in the extracellular matrix (ECM) was a key hallmark of LUAD invasion, which was validated by transcriptomic changes in independent tissue samples. Furthermore, several of these ECM genes were significantly associated with LUAD prognosis. Based on these findings, we hypothesized that epigenetic alterations during LUAD progression may drive these ECM changes, and that subsequent remodeling of the immune microenvironment may also contribute to the invasive process.
Conclusions:
Our integrated analysis demonstrated that epigenetic and transcriptomic dysregulation-induced ECM alterations were critical for LUAD invasion. Specifically, key ECM genes, including AGER and CGNL1, were identified as central regulators of invasion and thus represent promising therapeutic targets for LUAD.
Insights
Tumor invasion in lung adenocarcinoma (LUAD) is driven by epigenetic and transcriptomic changes affecting the extracellular matrix (ECM). Key ECM genes like AGER and CGNL1 are critical for invasion and offer potential therapeutic targets for LUAD.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Tumor invasion is a critical step in cancer progression and a key therapeutic target.
- The molecular mechanisms of lung adenocarcinoma (LUAD) invasion are not fully understood.
- Investigating transcriptomic and epigenetic alterations is crucial for elucidating LUAD invasion.
Purpose of the Study:
- To investigate transcriptomic and epigenetic alterations during LUAD invasion.
- To identify key biological processes and genes involved in LUAD invasion.
- To explore the clinical relevance of identified genes in LUAD prognosis.
Main Methods:
- RNA sequencing (RNA-seq) of invasive and non-invasive LUAD subtypes.
- Analysis of differentially expressed genes (DEGs) and enriched biological pathways.
- Chromatin immunoprecipitation sequencing (ChIP-seq) for H3K27ac.
- Survival analysis using The Cancer Genome Atlas (TCGA) database.
Main Results:
- Extracellular matrix (ECM) alterations are a hallmark of LUAD invasion.
- Transcriptomic analysis revealed significant ECM gene changes associated with LUAD prognosis.
- Epigenetic alterations potentially drive ECM changes during LUAD progression.
Conclusions:
- Epigenetic and transcriptomic dysregulation drives ECM alterations critical for LUAD invasion.
- Key ECM genes, including AGER and CGNL1, are central regulators of LUAD invasion.
- AGER and CGNL1 represent promising therapeutic targets for lung adenocarcinoma.
