scholarly journals Heterogeneity and targeted therapy-induced adaptations in lung cancer revealed by longitudinal single-cell RNA sequencing

2019 ◽  
Author(s):  
Ashley Maynard ◽  
Caroline E. McCoach ◽  
Julia K. Rotow ◽  
Lincoln Harris ◽  
Franziska Haderk ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Targeted Therapy ◽  
Single Cell ◽  
Cancer Cells ◽  
Rna Sequencing ◽  
Clinical Outcomes ◽  
Residual Disease ◽  
Metastatic Cancer ◽  
Immunosuppressive Cell ◽  
Single Cell Rna Sequencing

Lung cancer, the leading cause of cancer mortality, exhibits heterogeneity that enables adaptability, limits therapeutic success, and remains incompletely understood. Single-cell RNA sequencing (scRNAseq) of metastatic lung cancer was performed using 44 tumor biopsies obtained longitudinally from 27 patients before and during targeted therapy. Over 20,000 cancer and tumor microenvironment (TME) single-cell profiles exposed a rich and dynamic tumor ecosystem. scRNAseq of cancer cells illuminated targetable oncogenes beyond those detected clinically. Cancer cells surviving therapy as residual disease (RD) expressed an alveolar-regenerative cell signature suggesting a therapy-induced primitive cell state transition, whereas those present at on-therapy progressive disease (PD) upregulated kynurenine, plasminogen, and gap junction pathways. Active T-lymphocytes and decreased macrophages were present at RD and immunosuppressive cell states characterized PD. Biological features revealed by scRNAseq were biomarkers of clinical outcomes in independent cohorts. This study highlights how therapy-induced adaptation of the multi-cellular ecosystem of metastatic cancer shapes clinical outcomes.

Single-cell RNA-sequencing of migratory breast cancer cells: discovering genes associated with cancer metastasis

The Analyst ◽  
2019 ◽  
Vol 144 (24) ◽  
pp. 7296-7309 ◽  
Author(s):  
Yu-Chih Chen ◽  
Saswat Sahoo ◽  
Riley Brien ◽  
Seungwon Jung ◽  
Brock Humphries ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Single Cell ◽  
Cancer Cells ◽  
Rna Sequencing ◽  
Breast Cancer Cells ◽  
Cancer Metastasis ◽  
Tumor Formation ◽  
Single Cell Rna Sequencing ◽  
Migratory Cells

We enriched migratory breast cancer cells with enhanced tumor formation and metastasis capability using microfluidics and performed single-cell RNA-sequencing to identify unique EMT and CSC signature of migratory cells.

scholarly journals Single-cell RNA sequencing in human lung cancer

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Zhi-Xiong Chong ◽  
Wan-Yong Ho ◽  
Swee-Keong Yeap ◽  
Mong-Lien Wang ◽  
Yueh Chien ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Single Cell ◽  
Rna Sequencing ◽  
Human Lung ◽  
Human Lung Cancer ◽  
Single Cell Rna Sequencing

Abstract A09: Single-cell RNA sequencing reveals phenotypic plasticity of drug tolerant, clonal populations of cancer cells

2015 ◽  
Author(s):  
Fernando Lopez-Diaz ◽  
Mei-Chong Wendy Lee ◽  
Muhammad Tariq ◽  
Shahid Khan ◽  
Yelena Dayn ◽  
...  
Keyword(s):  
Phenotypic Plasticity ◽  
Single Cell ◽  
Cancer Cells ◽  
Rna Sequencing ◽  
Single Cell Rna Sequencing

scholarly journals Identification of a targetable KRAS-mutant epithelial population in non-small cell lung cancer

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Giorgia Maroni ◽  
Mahmoud A. Bassal ◽  
Indira Krishnan ◽  
Chee Wai Fhu ◽  
Virginia Savova ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Targeted Therapy ◽  
Single Cell ◽  
Murine Model ◽  
Tumor Heterogeneity ◽  
Small Cell ◽  
Small Cell Lung ◽  
Murine Lung ◽  
Single Cell Rna Sequencing

AbstractLung cancer is the leading cause of cancer deaths. Tumor heterogeneity, which hampers development of targeted therapies, was herein deconvoluted via single cell RNA sequencing in aggressive human adenocarcinomas (carrying Kras-mutations) and comparable murine model. We identified a tumor-specific, mutant-KRAS-associated subpopulation which is conserved in both human and murine lung cancer. We previously reported a key role for the oncogene BMI-1 in adenocarcinomas. We therefore investigated the effects of in vivo PTC596 treatment, which affects BMI-1 activity, in our murine model. Post-treatment, MRI analysis showed decreased tumor size, while single cell transcriptomics concomitantly detected near complete ablation of the mutant-KRAS-associated subpopulation, signifying the presence of a pharmacologically targetable, tumor-associated subpopulation. Our findings therefore hold promise for the development of a targeted therapy for KRAS-mutant adenocarcinomas.

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

2022 ◽  
Vol 7 (1) ◽  
Author(s):  
Li Zhang ◽  
Yiming Zhang ◽  
Chengdi Wang ◽  
Ying Yang ◽  
Yinyun Ni ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Single Cell ◽  
Rna Sequencing ◽  
Squamous Carcinoma ◽  
Specific Gene ◽  
Sequencing Analysis ◽  
Basal Cells ◽  
Functional Roles ◽  
Pathologic Features ◽  
Single Cell Rna Sequencing

AbstractLung 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.

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