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Translating Gene Signatures Into a Pathologic Feature: Tumor Necrosis Predicts Disease Relapse in Operable and Stage
Emily Pei-Ying Lin1, Tzu-Hung Hsiao1, Jo-Yang Lu1
1Emily Pei-Ying Lin, Tzu-Hung Hsiao, and Pan-Chyr Yang, National Taiwan University Hospital; Tzu-Pin Lu, National Taiwan University; Emily Pei-Ying Lin, Tzu-Hung Hsiao, Jo-Yang Lu, Siao-Han Wong, Konan Peck, and Pan-Chyr Yang, Academia Sinica, Taipei; Tzu-Hung Hsiao, Taichung Veterans General Hospital, Taichung, Taiwan; and Takashi Takahashi, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Gene signatures for cell cycle, hypoxia, and mTOR pathways can predict lung adenocarcinoma relapse. These signatures translate to tumor necrosis, a pathologic feature aiding risk stratification for early-stage lung cancer patients.
Area of Science:
- Oncology
- Molecular Biology
- Pathology
Background:
- High 5-year relapse rates in stage I lung adenocarcinoma necessitate improved risk stratification.
- Current methods may not fully capture the heterogeneity of early-stage lung adenocarcinoma.
Purpose of the Study:
- To assess if gene signatures can be translated into a pathologic feature for enhanced disease stratification in lung adenocarcinoma.
- To investigate the interdependence and risk stratification power of cell cycle, hypoxia, and mammalian target of rapamycin (mTOR) gene signatures.
Main Methods:
- Investigated three gene signatures (cell cycle, hypoxia, mTOR) in multiple lung adenocarcinoma and squamous cell carcinoma cohorts.
- Validated the translation of gene signatures to tumor necrosis in The Cancer Genome Atlas (TCGA) lung adenocarcinoma cohort.
- Performed integrative analyses using TCGA and The Cancer Protein Atlas data to link signature scores to pathway activity.
Main Results:
- Gene signatures were interdependent in lung adenocarcinoma but not squamous cell carcinoma.
- Higher signature activities were observed in necrosis-positive tumors.
- Signatures stratified patients into distinct risk groups, independent of age and stage, and tumor necrosis predicted survival outcomes.
Conclusions:
- Gene signatures can be translated into the pathologic feature of tumor necrosis.
- Tumor necrosis, informed by gene signatures, possesses risk stratification ability for operable, stage I lung adenocarcinomas.
