PMID- 35135134 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220209 IS - 2473-4284 (Electronic) IS - 2473-4284 (Linking) VI - 2 DP - 2018 Nov TI - Translating Gene Signatures Into a Pathologic Feature: Tumor Necrosis Predicts Disease Relapse in Operable and Stage I Lung Adenocarcinoma. PG - 1-13 LID - 10.1200/PO.18.00043 [doi] AB - PURPOSE: The high 5-year disease relapse rate in patients with stage I lung adenocarcinoma indicates the need for additional risk stratification parameters. This study assessed whether gene signatures translate into a pathologic feature for better disease stratification. MATERIALS AND METHODS: The mutual interdependence and risk stratification power of three gene signatures, cell cycle, hypoxia, and mammalian target of rapamycin (mTOR), were investigated in nine cohorts of patients with lung adenocarcinoma and five cohorts of patients with lung squamous cell carcinoma. The translation from gene signatures to a pathologic feature, tumor necrosis, was validated in The Cancer Genome Atlas lung adenocarcinoma cohort. The translation of signature score to pathway activity was further investigated by integrative analyses using The Cancer Genome Atlas and The Cancer Protein Atlas lung adenocarcinoma data sets. RESULTS: The results showed that the three gene signatures were mutually interdependent in lung adenocarcinoma but not in lung squamous cell carcinoma. The signature activities were higher in necrosis-positive tumors than in necrosis-negative tumors. The signature score correlated with the expression level of the representative protein that implicated the activity of each pathway. These signatures stratified patients with operable and stage I lung adenocarcinomas into different risk groups independent of age and stage. Furthermore, the signatures translated to a pathologic feature, tumor necrosis, which predicted shorter overall and relapse-free survival in patients with operable and stage I lung adenocarcinomas. CONCLUSION: This study showed that gene signatures could translate into a pathologic feature, tumor necrosis, with risk stratification ability in patients with operable and stage I lung adenocarcinomas. FAU - Lin, Emily Pei-Ying AU - Lin EP AD - Emily 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. FAU - Hsiao, Tzu-Hung AU - Hsiao TH AD - Emily 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. FAU - Lu, Jo-Yang AU - Lu JY AD - Emily 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. FAU - Wong, Siao-Han AU - Wong SH AD - Emily 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. FAU - Lu, Tzu-Pin AU - Lu TP AD - Emily 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. FAU - Peck, Konan AU - Peck K AD - Emily 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. FAU - Takahashi, Takashi AU - Takahashi T AD - Emily 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. FAU - Yang, Pan-Chyr AU - Yang PC AD - Emily 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. LA - eng PT - Journal Article PL - United States TA - JCO Precis Oncol JT - JCO precision oncology JID - 101705370 SB - IM EDAT- 2018/11/01 00:00 MHDA- 2018/11/01 00:01 CRDT- 2022/02/09 01:00 PHST- 2022/02/09 01:00 [entrez] PHST- 2018/11/01 00:00 [pubmed] PHST- 2018/11/01 00:01 [medline] AID - 10.1200/PO.18.00043 [doi] PST - ppublish SO - JCO Precis Oncol. 2018 Nov;2:1-13. doi: 10.1200/PO.18.00043.