2024 World Conference on Lung Cancer (WCLC) - ePosters-EP.07F.04 Differences in High-Order, Three-Dimensional Chromatin Structure Between Tumor and Adjacent Normal Tissues in Lung Adenocarcinoma

EP.07F.04 Differences in High-Order, Three-Dimensional Chromatin Structure Between Tumor and Adjacent Normal Tissues in Lung Adenocarcinoma

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The study by Li Li and Shuanghu Yuan investigates the differences in the three-dimensional (3-D) chromatin structure between tumor and adjacent normal tissues in lung adenocarcinoma (LUAD). Researchers enrolled 30 patients and analyzed paired samples of tumor and adjacent normal tissues, focusing on chromosomal interactions and structures.<br /><br />The team used Hi-C chromosome conformation capture techniques and RNA sequencing to profile chromatin interactions and lncRNA expression. Notably, Hi-C heatmaps identified specific interchromosomal interactions distinct to tumor tissues, such as interactions between chromosomes 6 and 8, and chromosomes 13 and 15. Circos plots demonstrated increased interactions from chromosome 17 to 11 and from chromosome 15 to 5 in tumor tissues. Conversely, chromosome X had decreased interaction with chromosomes 2 and 3 in tumor samples.<br /><br />The study found that tumor tissues exhibited a higher number of topologically associated domains (TADs) that merged and shifted at intra-TAD boundaries in chromosomes 11, 15, and X. A Pearson correlation matrix further indicated an increase in component A/B location switching, especially in chromosome X, where over 40% of the A compartment shifted to the B compartment, suggesting a change from active to inactive gene loci.<br /><br />RNA sequencing revealed an up-regulation of long non-coding RNAs (lncRNAs) in chromosomes 15 and X within tumor tissues. Pathway enrichment analyses highlighted significant enrichment of differentially expressed genes in biological regulation and metabolic processes.<br /><br />The research concludes that understanding chromatin structures could help identify biomarkers and molecular targets for targeted gene therapies, aiding in a deeper comprehension of the regulatory networks of LUAD. The top up-regulated lncRNAs were located in shifted TAD boundaries of chromosomes 11, 15, and X, crucial for their altered function and regulation in tumor progression.

Asset Subtitle

Li Li

Meta Tag

Speaker Li Li

Topic Early-Stage Non-small Cell Lung Cancer

Keywords

3-D chromatin structure

lung adenocarcinoma

Hi-C chromosome conformation

lncRNA expression

interchromosomal interactions

topologically associated domains

chromosome X

RNA sequencing

pathway enrichment

gene therapies