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Updated: Jun 4, 2026
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
An integrative investigation on significant mutations and their down-stream pathways in lung squamous cell carcinoma
Zongang Liu1, Meiyan Deng1, Lin Wu2
1Department of Thoracic Surgery, Shengjing Hospital of China Medical University, No.36 Sanhao Street, Heping District Shenyang, Liaoning, 110004, People's Republic of China.
Background:
Molecular mechanism of lung squamous cell carcinoma (LUSC) remains poorly understood, hampering effective targeted therapies or precision diagnosis about LUSC. We devised an integrative framework to investigate on the molecular patterns of LUSC by systematically mining the genomic, transcriptional and clinical information.
Methods:
We utilized the genomics and transcriptomics data for the LUSC cohorts in The Cancer Genome Atlas.. Both kinds of omics data for 33 types of cancers were downloaded from The NCI's Genomic Data Commons (GDC) (https://gdc.cancer.gov/about-data/publications/pancanatlas). The genomics data were processed in mutation annotation format (maf), and the transcriptomics data were determined by RNA-seq method. Mutation significance was estimated by MutSigCV. Prognosis analysis was based on the cox proportional hazards regression (Coxph) model.
Results:
Significant somatic mutated genes (SMGs) like NFE2L2, RASA1 and COL11A1 and their potential down-stream pathways were recognized. Furthermore, two LUSC-specific and prognosis-meaningful subtypes were identified. Interestingly, the good prognosis subtype was enriched with mutations in CUL3/KEAP1/NRF2 pathway and with markedly suppressed expressions of multiple down-stream pathways like epithelial mesenchymal transition. The subtypes were verified by the other two cohorts. Additionally, primarily regulated down-stream elements of different SMGs were also estimated. NFE2L2, KEAP1 and RASA1 mutations showed remarkable effects on the subtype-determinant gene expressions, especially for the inflammatory relevant genes.
Conclusions:
This study supplies valuable references on potential down-stream processes of SMGs and an alternative way to classify LUSC.
Insights
This study identifies key molecular patterns in lung squamous cell carcinoma (LUSC) by analyzing genomic and transcriptomic data. It reveals two distinct LUSC subtypes with prognostic significance, offering new diagnostic and therapeutic insights.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- The molecular mechanisms driving lung squamous cell carcinoma (LUSC) are not fully understood, limiting targeted therapies and precise diagnosis.
- An integrative framework was developed to analyze genomic, transcriptional, and clinical data for LUSC.
Purpose of the Study:
- To investigate the molecular patterns of LUSC.
- To identify potential therapeutic targets and diagnostic markers for LUSC.
Main Methods:
- Utilized genomics and transcriptomics data from The Cancer Genome Atlas (TCGA) LUSC cohorts.
- Employed MutSigCV for mutation significance and Cox proportional hazards regression for prognosis analysis.
- Analyzed RNA-seq and mutation annotation format (maf) data.
Main Results:
- Identified significant somatic mutated genes (SMGs) including NFE2L2, RASA1, and COL11A1, along with their downstream pathways.
- Discovered two LUSC subtypes with prognostic value, one associated with the CUL3/KEAP1/NRF2 pathway and suppressed epithelial-mesenchymal transition.
- Confirmed that mutations in NFE2L2, KEAP1, and RASA1 impact gene expression, particularly inflammatory genes.
Conclusions:
- Provides valuable insights into the downstream processes of SMGs in LUSC.
- Offers an alternative molecular classification system for LUSC, aiding in diagnosis and treatment strategies.
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