Lung adenocarcinoma(LUAD)and squamous carcinoma(LUSC)are two major subtypes of non-small cell lung cancer with distinct pathologic features and treatment paradigms.The heterogeneity can be attributed to genetic,transc...Lung adenocarcinoma(LUAD)and squamous carcinoma(LUSC)are two major subtypes of non-small cell lung cancer with distinct pathologic features and treatment paradigms.The heterogeneity can be attributed to genetic,transcriptional,and epigenetic parameters.Here,we established a multi-omics atlas,integrating 52 single-cell RNA sequencing and 2342 public bulk RNA sequencing.We investigated their differences in genetic amplification,cellular compositions,and expression modules.We revealed that LUAD and LUSC contained amplifications occurring selectively in subclusters of AT2 and basal cells,and had distinct cellular composition modules associated with poor survival of lung cancer.Malignant and stage-specific gene analyses further uncovered critical transcription factors and genes in tumor progression.Moreover,we identified subclusters with proliferating and differentiating properties in AT2 and basal cells.Overexpression assays of ten genes,including sub-cluster markers AQP5 and KPNA2,further indicated their functional roles,providing potential targets for early diagnosis and treatment in lung cancer.展开更多
基金This study was funded by the National Key Research and Development Program of China,Stem Cell and Translational Research(2017YFA0106800 and 2017YFA0106500)the National Natural Science Foundation of China(grants 81974363,81772478,81871890,81722004 and 91859203).
文摘Lung adenocarcinoma(LUAD)and squamous carcinoma(LUSC)are two major subtypes of non-small cell lung cancer with distinct pathologic features and treatment paradigms.The heterogeneity can be attributed to genetic,transcriptional,and epigenetic parameters.Here,we established a multi-omics atlas,integrating 52 single-cell RNA sequencing and 2342 public bulk RNA sequencing.We investigated their differences in genetic amplification,cellular compositions,and expression modules.We revealed that LUAD and LUSC contained amplifications occurring selectively in subclusters of AT2 and basal cells,and had distinct cellular composition modules associated with poor survival of lung cancer.Malignant and stage-specific gene analyses further uncovered critical transcription factors and genes in tumor progression.Moreover,we identified subclusters with proliferating and differentiating properties in AT2 and basal cells.Overexpression assays of ten genes,including sub-cluster markers AQP5 and KPNA2,further indicated their functional roles,providing potential targets for early diagnosis and treatment in lung cancer.
