2024 World Conference on Lung Cancer (WCLC) - Posters-P1.03B.01 Multi-Omics Profiling Reveals the Genomic Origin and Adeno-Squamous Transdifferentiation Mechanism in Adenosquamous Carcinoma

P1.03B.01 Multi-Omics Profiling Reveals the Genomic Origin and Adeno-Squamous Transdifferentiation Mechanism in Adenosquamous Carcinoma

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The study titled "Multi-Omics Profiling Reveals the Genomic Origin and Adeno-Squamous Transdifferentiation Mechanism in Adenosquamous Carcinoma" by Gen Lin and colleagues, investigates the rare type of non-small-cell lung cancer known as adenosquamous carcinoma (ASC), which accounts for 0.4-4% of cases and is associated with poor prognosis. The research aims to fill the knowledge gap regarding the genomic and molecular mechanisms of adeno-squamous transdifferentiation in lung ASC through comprehensive multi-omics analysis.<br /><br />Methods involved examining 69 samples from 31 ASC patients and included whole-exome sequencing, whole-genome methylation profiling, transcriptomics, single-cell RNA sequencing, and spatial transcriptomics. Comparisons were also made with pure Lung Adenocarcinoma and pure Squamous Cell Carcinoma samples to assess differences and similarities in genetic and epigenetic profiles.<br /><br />Key findings revealed that adenocarcinoma (AC) and squamous cell carcinoma (SCC) components of ASC shared similar genomic mutation landscapes, suggesting a common genomic origin. Differential methylation analysis indicated hypomethylation at the TP63 gene locus correlated with increased RNA expression, and immune infiltration patterns indicated a shift from immune-infiltrated to immune-desert phenotypes during the ASC transformation process.<br /><br />A notable discovery was the role of IL36G in the transdifferentiation process; it acts as a critical player and potential therapeutic target due to its high expression levels in SCC components and its positive correlation with squamous marker P63. This suggests IL36G's involvement in promoting adeno-squamous differentiation.<br /><br />In conclusion, the study highlights IL36G as a potential target for new ASC treatments and underscores the effectiveness of multi-omic approaches for uncovering novel biomarkers and therapeutic targets. Future research should further explore the detailed pathways and mechanisms in ASC to improve patient outcomes.

Asset Subtitle

Gen Lin

Meta Tag

Speaker Gen Lin

Topic Tumor Biology – Translational Biology

Keywords

Multi-Omics Profiling

Adenosquamous Carcinoma

Non-Small-Cell Lung Cancer

Genomic Origin

Transdifferentiation Mechanism

Whole-Exome Sequencing

Methylation Profiling

IL36G

Immune Infiltration

Therapeutic Targets