Multiregion gene expression profiling reveals heterogeneity in molecular subtypes and immunotherapy response signatures in lung cancer. (June 2018)

• Record Type: Journal Article
• Authors: Lee, Won-Chul; Diao, Lixia; Wang, Jing; Zhang, Jianhua; Roarty, Emily; Varghese, Susan; Chow, Chi-Wan; Fujimoto, Junya; Behrens, Carmen; Cascone, Tina; Peng, Weiyi; Kalhor, Neda; Moran, Cesar; Weissferdt, Annikka; Johnson, Faye; William, William; Swisher, Stephen; Lee, J.; Hong, Waun; Heymach, John; Wistuba, Ignacio; Futreal, P.; Zhang, Jianjun
• Is Part Of: Modern pathology. Volume 31:Number 6(2018)
• Page Start: 947
• Page End: 955
• Publication Date: 2018-06
• Subjects: Pathology -- Periodicals; Diagnosis, Laboratory -- Periodicals; Pathologie -- Périodiques; Diagnostics biologiques -- Périodiques; Diagnosis, Laboratory; Pathology; Pathology -- Abstracts; Pathology -- Periodicals; Periodicals; Electronic journals; 616.07
• DOI: 10.1038/s41379-018-0029-3
• Languages: English
• ISSNs: 0893-3952

Abstract

Abstract Intra-tumor heterogeneity may be present at all molecular levels. Genomic intra-tumor heterogeneity at the exome level has been reported in many cancer types, but comprehensive gene expression intra-tumor heterogeneity has not been well studied. Here, we delineated the gene expression intra-tumor heterogeneity by exploring gene expression profiles of 35 tumor regions from 10 non-small cell lung cancer tumors (three or four regions/tumor), including adenocarcinoma, squamous cell carcinoma, large-cell carcinoma, and pleomorphic carcinoma of the lung. Using Affymetrix Gene 1.0 ST arrays, we generated the gene expression data for every sample. Inter-tumor heterogeneity was generally higher than intra-tumor heterogeneity, but some tumors showed a substantial level of intra-tumor heterogeneity. The analysis of various clinically relevant gene expression signatures including molecular subtype, epithelial-to-mesenchymal transition, and anti-PD-1 resistance signatures also revealed heterogeneity between different regions of the same tumor. The gene expression intra-tumor heterogeneity we observed was associated with heterogeneous tumor microenvironments represented by stromal and immune cells infiltrated. Our data suggest that RNA-based prognostic or predictive molecular tests should be carefully conducted in consideration of the gene expression intra-tumor heterogeneity.