2023 World Conference on Lung Cancer (Posters)-EP06.03. Elucidating Tumor Heterogeneity from Spatially Resolved Transcriptomics in ALK-Rearranged Non-small Cell Lung Cancer

EP06.03. Elucidating Tumor Heterogeneity from Spatially Resolved Transcriptomics in ALK-Rearranged Non-small Cell Lung Cancer - PDF(Slides)

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A study was conducted to investigate tumor heterogeneity in ALK-rearranged non-small cell lung cancer (NSCLC) through spatially resolved transcriptomics analysis. The study aimed to understand the mechanisms contributing to treatment resistance and to identify potential ways to overcome resistance to targeted therapies for ALK-positive tumors.<br /><br />The researchers collected 10 tissue specimens from patients with ALK-rearranged NSCLC and performed spatial transcriptomics analysis. They used H&E staining to visualize the heterogeneity in gene expression patterns within the tissue sections. The data was processed using dimensionality reduction and clustering methods.<br /><br />The analysis revealed distinct clusters of cells in the tumor samples. Cluster 9 was identified as myofibroblastic cancer-associated fibroblasts (myoCAFs) characterized by high expression of MMP11 and COL1A1 genes involved in generating collagenous extracellular matrix. Cluster 5 appeared to be a B cell-rich area, while cluster 8 showed high expression of the OLFML3 gene associated with vascular tissue remodeling and angiogenesis.<br /><br />Further analysis using trajectory and pseudotime analysis confirmed the presence of two branches in the tumor region. Deconvolution analysis using the CARD R package identified cluster 9 as a myofibroblast-rich region and cluster 5 as a B cell-rich region.<br /><br />The study highlights the intratumoral heterogeneity in ALK-rearranged lung cancer and how these tumors progress within the tumor. Understanding the heterogeneity and identifying different cell types within the tumor could provide insights into treatment resistance and help develop better strategies to overcome resistance to targeted therapies.<br /><br />The research was supported by grants from the National Research Foundation of Korea. The findings could potentially be linked to clinical conditions and contribute to improved treatment outcomes for patients with ALK-rearranged NSCLC.

Asset Subtitle

JungHan Oh

Meta Tag

Speaker JungHan Oh

Topic Pathology & Biomarkers: Genetic Biomarkers

Keywords

tumor heterogeneity

ALK-rearranged non-small cell lung cancer

spatially resolved transcriptomics analysis

treatment resistance

targeted therapies

gene expression patterns

myofibroblastic cancer-associated fibroblasts

B cell-rich area

vascular tissue remodeling

intratumoral heterogeneity