Yuanhe Wang1, Jianyi Li1, Cheng Shao1, Xiaojie Tang1,2, Yukun Du1, Tongshuai Xu1, Zheng Zhao1, Huiqiang Hu1, Yingyi Sheng1, Chuan Hu3, Yongming Xi4. 1. Department of Orthopaedic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266071, China. 2. Department of Spinal Surgery, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, 264100, China. 3. Department of Orthopaedic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266071, China. 2018020760@qdu.edu.cn. 4. Department of Orthopaedic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266071, China. xym700118@163.com.
Abstract
BACKGROUND: Autophagy-related genes (ARGs) have been confirmed to have an important role in tumorigenesis and tumor microenvironment formation. Nevertheless, a systematic analysis of ARGs and their clinical significance in sarcoma patients is lacking. METHODS: Gene expression files from The Cancer Genome Atlas (TCGA) database and Genotype-Tissue Expression (GTEx) were used to select differentially expressed genes (DEGs). Differentially expressed ARGs (DEARGs) were determined by matching the DEG and HADb gene sets, which were evaluated by functional enrichment analysis. Unsupervised clustering of the identified DEARGs was conducted, and associations with tumor microenvironment (TME), immune checkpoints, and immune cells were analyzed simultaneously. Two prognostic signatures, one for overall survival (OS) and one for disease-free survival (DFS), were established and validated in an independent set. RESULTS: In total, 84 DEARGs and two clusters were identified. TME scores, five immune checkpoints, and several types of immune cells were found to be significantly different between two clusters. Two prognostic signatures incorporating DEARGs showed favorable discrimination and were successfully validated. Two nomograms combining signature and clinical variables were generated. The C-indexes were 0.818 and 0.747 for the OS and DFS nomograms, respectively. CONCLUSION: This comprehensive analyses of the ARG landscape in sarcoma showed novel ARGs related to carcinogenesis and the immune microenvironment. These findings have implications for prognosis and therapeutic responses, which reveal novel potential prognostic biomarkers, promote precision medicine, and provide potential novel targets for immunotherapy.
BACKGROUND: Autophagy-related genes (ARGs) have been confirmed to have an important role in tumorigenesis and tumor microenvironment formation. Nevertheless, a systematic analysis of ARGs and their clinical significance in sarcomapatients is lacking. METHODS: Gene expression files from The Cancer Genome Atlas (TCGA) database and Genotype-Tissue Expression (GTEx) were used to select differentially expressed genes (DEGs). Differentially expressed ARGs (DEARGs) were determined by matching the DEG and HADb gene sets, which were evaluated by functional enrichment analysis. Unsupervised clustering of the identified DEARGs was conducted, and associations with tumor microenvironment (TME), immune checkpoints, and immune cells were analyzed simultaneously. Two prognostic signatures, one for overall survival (OS) and one for disease-free survival (DFS), were established and validated in an independent set. RESULTS: In total, 84 DEARGs and two clusters were identified. TME scores, five immune checkpoints, and several types of immune cells were found to be significantly different between two clusters. Two prognostic signatures incorporating DEARGs showed favorable discrimination and were successfully validated. Two nomograms combining signature and clinical variables were generated. The C-indexes were 0.818 and 0.747 for the OS and DFS nomograms, respectively. CONCLUSION: This comprehensive analyses of the ARG landscape in sarcoma showed novel ARGs related to carcinogenesis and the immune microenvironment. These findings have implications for prognosis and therapeutic responses, which reveal novel potential prognostic biomarkers, promote precision medicine, and provide potential novel targets for immunotherapy.
Authors: Nabil Ahmed; Vita S Brawley; Meenakshi Hegde; Catherine Robertson; Alexia Ghazi; Claudia Gerken; Enli Liu; Olga Dakhova; Aidin Ashoori; Amanda Corder; Tara Gray; Meng-Fen Wu; Hao Liu; John Hicks; Nino Rainusso; Gianpietro Dotti; Zhuyong Mei; Bambi Grilley; Adrian Gee; Cliona M Rooney; Malcolm K Brenner; Helen E Heslop; Winfried S Wels; Lisa L Wang; Peter Anderson; Stephen Gottschalk Journal: J Clin Oncol Date: 2015-03-23 Impact factor: 44.544
Authors: Alexandria C Rutkovsky; Elizabeth S Yeh; Stephen T Guest; Victoria J Findlay; Robin C Muise-Helmericks; Kent Armeson; Stephen P Ethier Journal: BMC Cancer Date: 2019-05-23 Impact factor: 4.430