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Nan Fang

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    MA04 - Models and Biomarkers (ID 122)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Biology
    • Presentations: 1
    • Now Available
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      MA04.02 - Molecular Profiling of Adenocarcinoma and Squamous Cell Lung Cancer at Single Cell Resolution (Now Available) (ID 1358)

      13:30 - 15:00  |  Author(s): Nan Fang

      • Abstract
      • Presentation
      • Slides


      Adenocarcinoma and squamous are two main subgroups of lung cancer: adenocarcinoma (ADC) accounts for 30-50% and squamous cell carcinoma (SCC) accounts for nearly 30% of all cases respectively. ADC and SCC have different pathological phenotypes and respond differently to various therapies, including immunotherapy. However, the underlying molecular mechanism of such differentiated drug responses still needs to be further characterized.


      To achieve high resolution of both tumor cells and their tumor microenvironment (TME), we used single cell RNA sequencing method to characterize ADC and SCC tumors from Stage IV NSCLC patients. Tissue biopsy samples from 21 patients (12 patients with ADC, 9 with SCC) were collected. For each sample, single cell RNA sequencing was performed on an average of 1930 cells. A graph-based clustering approach was used to classify cells into different cell types based on their gene expression patterns. The cellular subtypes of both cancer cells and TME in ADC and SCC samples were analyzed.


      ADC and SCC show distinct patterns at single cell resolution. Cancer cells from all ADC patients form two closely related clusters, while cancer cells from SCC patients show high intra-and inter-patient heterogeneity. Gene Ontology (GO) analysis demonstrated that ADC samples are enriched in genes of neutrophil degranulation and activation, while SCCs are enriched in genes related to epidermal cell differentiation and glutathione metabolic process. Genes related to cancer progression and metastasis, such as LSD1 and FASCIN, are normally expressed at higher level in SCC than in ADC. Furthermore, ADC samples contain higher percentage of a specific myeloid cell population, while SCC has higher percentage of fibroblasts, demonstrating the difference also in TMEs of ACD versus SCC.


      The significantly higher level of heterogeneity for SCC can be a possible reason for poor responses to standard lung cancer therapies, including immunotherapy. Accurate characterization of SCC with single cell resolution could hold the key to more effective therapeutic strategies.

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