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

Abstract

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.

Single-Cell Profiling of Tumor Microenvironment Heterogeneity in Osteosarcoma Identifies a Highly Invasive Subcluster for Predicting Prognosis

“…ScRNA-seq gets more detailed information at the cellular level, and bulk RNA-seq and scRNA-seq have certain consistency. Combining the scRNA-seq with existing bulk data from large cohorts can help decipher the molecular mechanisms of OS progression and metastasis ( 58 ). Based on the above research results, we established a metastasis-associated risk assessment model for OS, which considered five genes: BNIP3, CPE, DKK1, EFEMP2 and GALNT14.…”

Immune infiltration landscape on prognosis and therapeutic response and relevant epigenetic and transcriptomic mechanisms in lung adenocarcinoma

“…Eight immune cell types were notably linked with LUAD prognosis, of which B cells, eosinophils, iDCs, mast cells, T cells, Tem, and Tfh cells acted as risk factors, with Th2 cells as a protective factor. Genetic, epigenetic, cellular, and microenvironmental traits may impact cellular programs and result in diverse pathogeneses of LUAD ( 30 ). Here, two immune infiltration-based subtypes were proposed in LUAD, with disparate OS outcomes.…”

The dynamic dysregulated network identifies stage-specific markers during lung adenocarcinoma malignant progression and metastasis

“…In recent years, increasing research progress on LUAD have been achieved by facilitating the analysis of single-cell transcriptome sequencing. For example, single-cell transcriptomic studies revealed substantial heterogeneity in cellular composition of the tumor microenvironment 8 , 46 , 47 and molecular properties in primary and metastatic LUAD. 48 , 49 Liu et al.…”