Novel mutational landscapes and expression signatures of lung squamous cell carcinoma

Donghai Xiong, Jing Pan, Yuxin Yin, Hui Jiang, Eva Szabo, Ronald A. Lubet, Yian Wang, Ming You

    Research output: Contribution to journalArticlepeer-review

    18 Scopus citations

    Abstract

    Lung squamous cell carcinoma (LUSC) is a major subtype of Non-Small Cell Lung Cancer. To increase our understanding of the LUSC pathobiology, we performed exome sequencing and RNA-seq in 16 murine carcinogen-induced LUSC tumors and 8 normal murine lung tissue samples. Additionally, we conducted single-cell RNAseq on two independent tumors from the same murine model. We identified a list of 59 cancer genes recurrently mutated in the mice LUSC tumors, 47 (80%) of which were also mutated in human LUSCs. At the single cell level, we detected unique clonal mutation patterns for each of the two LUSC tumors, being initiated from clones carrying the mutant Igfbp7 and Trp53 genes, respectively. We also identified an expression signature serving as an effective classifier for LUSC tumors and a strong predictor of survival outcomes of lung cancer patients. Lastly, we found that some of the mutant LUSC genes were associated with the significantly altered tumoral expression of inhibitory immune checkpoint genes such as PD-L1, VISTA, TIM3 and LAG3 in human LUSCs. The novel findings of clonal evolution, mutational landscapes and expression signatures of LUSC suggested new targets for the overall LUSC therapy and the immunotherapy of LUSC.

    Original languageEnglish (US)
    Pages (from-to)7424-7441
    Number of pages18
    JournalOncotarget
    Volume9
    Issue number7
    DOIs
    StatePublished - Jan 26 2018

    Keywords

    • Expression signature
    • Immunotherapy
    • LUSC (lung squamous cell carcinoma)
    • Somatic mutation
    • Tumor evolution

    ASJC Scopus subject areas

    • Oncology

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