2022 World Conference on Lung Cancer (ePosters)-EP16.04-013. Spatial Multi-Omics Landscape of Radiologically Preinvasive/Invasive Lesion in Part-Solid Lung Adenocarcinoma

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Researchers conducted a study to examine the distinct spatial structures of radiologically preinvasive/invasive lesions in part-solid lung adenocarcinoma. It is known that early-stage lung adenocarcinoma can present as a part-solid nodule in chest computed tomography, consisting of invasive and preinvasive lesions. However, there have been few studies on the characteristics of the tumor microenvironment (TME) in part-solid lung adenocarcinoma. The researchers constructed and analyzed high-resolution spatial transcriptomics of early-stage lung adenocarcinoma presented as part-solid nodules.<br /><br />The study involved analyzing spatial transcriptomic-genomic alterations in the preinvasive and invasive regions of lung adenocarcinoma. The spatial genomic and transcriptomic changes, as well as alterations in immune cell compositions, provided insights into the cancer evolution with TME changes in lung adenocarcinoma.<br /><br />The research included spatial transcriptome data from eight samples taken from four patients with part-solid nodules. Unsupervised clustering analysis and trajectory analysis across spots were performed to identify spatial transcriptomic characteristics. Additionally, single-cell RNA-seq data was used to estimate the composition of immune/stromal cells in each spot.<br /><br />The study found that there was no discernible variation in spatial transcriptomic characteristics between solid and ground-glass lesions. Malignancy-specific epithelium was common across all samples, while normal-like epithelium was more common in preinvasive lesions. CD8 T cells were primarily found near malignancy-specific epithelium, while CD4 T-helper cells were dispersed in areas without normal-like epithelium.<br /><br />In terms of genomic analysis, the researchers observed shared somatic mutations, including an EGFR L858R mutation, in all tumor regions. However, DNA copy numbers of certain chromosomes differed between invasive and preinvasive regions, suggesting a branched trajectory in the clonal evolution of the tumor. The clonal divergence of major clones in the invasive and preinvasive regions occurred after acquiring the EGFR activating mutation, and copy number alterations were acquired in clonal lineages of the invasive regions.<br /><br />Overall, this study provides insights into the spatial structures and characteristics of radiologically preinvasive and invasive lesions in part-solid lung adenocarcinoma, shedding light on the understanding of cancer evolution and progression in the tumor microenvironment.

Asset Subtitle

Kwon Joong Na

Meta Tag

Speaker Kwon Joong Na

Topic Tumour Biology and Biomarkers - Tumour Biology & Preclinical Studies

Keywords

part-solid lung adenocarcinoma

radiologically preinvasive/invasive lesions

tumor microenvironment (TME)

spatial transcriptomics

early-stage lung adenocarcinoma

high-resolution spatial transcriptomics

spatial genomic alterations

immune cell compositions

single-cell RNA-seq

clonal evolution of the tumor