Integrated single-cell RNA sequencing analysis reveals distinct cellular and transcriptional modules associated with survival in lung cancer

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.

The heterogeneous immune landscape between lung adenocarcinoma and squamous carcinoma revealed by single-cell RNA sequencing

A thorough interrogation of the immune landscape is crucial for immunotherapy strategy selection and prediction of clinical responses in non-small-cell lung cancer(NSCLC)patients.Single-cell RNA sequencing(scRNA-seq)techniques have prompted the opportunity to dissect the distinct immune signatures between lung adenocarcinoma(LUAD)and lung squamous cell carcinoma(LUSC),the two major subtypes of NSCLC.Here,we performed scRNA-seq on 72,475 immune cells from 40 samples of tumor and matched adjacent normal tissues spanning 19 NSCLC patients,and drew a systematic immune cell transcriptome atlas.Joint analyses of the distinct cellular compositions,differentilly expressed genes(DEGs),cell-cell interactions,pseudotime trajectory,transcriptomic factors and prognostic factors based on The Cancer Genome Atlas(TCGA),revealed the central roles of cytotoxic and effector T and NK cells and the distinct functional macrophages(Mo)subtypes in the immune microenvironment heterogeneity between LUAD and LUSC.The dominant subtype of Mo was FABP4-Mp in LUAD and SPP1-Mo in LUSC.Importantly,we identifieda novel lymphocyte-related Mo cluster,which we named SELENOP-Mo,and further established its antitumor role in both types,especially in LUAD.Our comprehensive depiction of the immune heterogeneity and definition of Mp clusters could help design personalized treatment for lung cancer patients in clinical practice.