2024 World Conference on Lung Cancer (WCLC) - Posters-P3.06F.06 Spatial Transcriptomic Profiling Reveals Molecular Patterns Associated with Poor Prognosis in ALK-Rearranged NSCLC Patients

P3.06F.06 Spatial Transcriptomic Profiling Reveals Molecular Patterns Associated with Poor Prognosis in ALK-Rearranged NSCLC Patients

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This study investigates molecular patterns linked to poor prognosis in patients with ALK-rearranged non-small cell lung cancer (NSCLC), primarily found in younger, non-smoking individuals with high metastasis rates. Utilizing Spatial Transcriptomics, the research reveals crucial insights into the tumor and its microenvironment, elucidating factors influencing adverse clinical outcomes.<br /><br />Key findings indicate a significant presence of cancer-associated fibroblast (CAF) markers in the stroma of both primary lung tumors and lymph node metastases. This fibro-genic environment enhances tumor progression and disrupts immune responses, a contrast to brain metastasis where these markers are absent. The study highlights the role of DNA damage and stress response pathways in driving accelerated extracellular matrix (ECM) remodeling, which compromises ECM integrity, fostering tumor progression and impairing immune surveillance within these tumors.<br /><br />Furthermore, differential gene expression analysis demonstrates that high-risk lymph node metastasis exhibits weakened immune mechanisms and tissue integrity within the tumor segment. Conversely, the stroma of high-risk patients shows an adaptive response, enhancing stress responses to DNA damage and immune defense. In particular, the olfactory signaling pathway was activated in high-risk lymph node tumors, while oxidative protection and ECM integrity pathways were suppressed.<br /><br />In the stromal segments of high-risk lymph node metastasis cases, significant activation of the "MET activates PTK2 signaling pathway" was noted, which correlates with cancer progression. Simultaneously, suppression of T cell activation and intracellular signaling pathways suggests a compromised immune defense and reduced intracellular communication.<br /><br />These molecular insights aid in understanding the mechanisms driving poor prognosis in ALK-rearranged NSCLC patients, underscoring the need for tailored therapeutic strategies targeting these underlying genetic and environmental factors.

Asset Subtitle

Warisa Khatoon

Meta Tag

Speaker Warisa Khatoon

Topic Pathology & Biomarkers

Keywords

ALK-rearranged NSCLC

Spatial Transcriptomics

cancer-associated fibroblasts

tumor microenvironment

extracellular matrix remodeling

immune surveillance

differential gene expression

MET PTK2 signaling

DNA damage response

therapeutic strategies