2023 World Conference on Lung Cancer (Posters)-P2.13. Spatially Resolved Transcriptomics deciphers Inter- and Intra-Tumor Heterogeneity of Small Cell Lung Cancer

P2.13. Spatially Resolved Transcriptomics deciphers Inter- and Intra-Tumor Heterogeneity of Small Cell Lung Cancer - PDF(Slides)

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Small cell lung cancer (SCLC) is a highly heterogeneous cancer with aggressive progression and poor prognosis. The current subtypes based on neuroendocrine differentiation and transcription factors are still controversial in terms of prognostic significance and clinical treatment correlation. In this study, the researchers aimed to define and decipher inter- and intra-tumor heterogeneity (ITH) in SCLC and explore its clinical relevance.<br /><br />The researchers used digital spatial profiling (DSP) to quantify the whole transcriptomes and calculate the ITH score at the RNA level. They also adopted deconvoluted algorithms to calculate immune infiltration and constructed a machine learning model to determine tumor heterogeneity and facilitate prognostic stratification. <br /><br />Using DSP RNA expression data from resected limited stage SCLC patients, the researchers differentiated intra-/inter-tumor heterogeneity subtypes and classified them into high-ITH, median-ITH, and low-ITH phenotypes. They also classified the patients into two distinct subgroups based on the complexity of the tumor microenvironment. The presence of high ITH was consistently associated with unfavorable prognoses and reduced responsiveness to immune-based therapies.<br /><br />The researchers also identified spatially resolved gene signatures that allow for patient risk stratification and validated them in multicenter bulk RNA sequencing cohorts.<br /><br />In conclusion, this study successfully deciphered the inter- and intra-tumor heterogeneity of SCLC and proposed a new framework for improving risk stratification and molecular classification. This framework shows promise in postoperative stratified management of limited stage SCLC patients and assessing the efficacy of immunotherapy in advanced stage patients.

Asset Subtitle

xujie Sun

Meta Tag

Speaker xujie Sun

Topic SCLC & Neuroendocrine Tumors: Biomarkers & Radiomics

Keywords

Small cell lung cancer

SCLC

neuroendocrine differentiation

transcription factors

prognostic significance

digital spatial profiling

immune infiltration

tumor microenvironment

gene signatures

immunotherapy