Comparative Transcriptome Analysis Quantifies Immune Cell Transcript Levels, Metastatic Progression, and Survival in Osteosarcoma.

Autor:	Scott MC; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.; Animal Cancer Care and Research Program, University of Minnesota, St. Paul, Minnesota.; Department of Veterinary Clinical Sciences, University of Minnesota College of Veterinary Medicine, St. Paul, Minnesota., Temiz NA; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.; Institute for Health Informatics, University of Minnesota, Minneapolis, Minnesota., Sarver AE; Department of Surgery, University of Minnesota School of Medicine, Minneapolis, Minnesota.; Department of Pediatrics, University of Minnesota School of Medicine, Minneapolis, Minnesota., LaRue RS; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.; Department of Medicine, University of Minnesota School of Medicine, Minneapolis, Minnesota., Rathe SK; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota., Varshney J; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota., Wolf NK; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.; Department of Genetics, Cell Biology and Development, University of Minnesota School of Medicine, Minneapolis, Minnesota., Moriarity BS; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.; Brain Tumor Program, University of Minnesota, Minneapolis, Minnesota.; Center for Genome Engineering, University of Minnesota, Minneapolis, Minnesota.; Department of Veterinary Population Medicine, University of Minnesota College of Veterinary Medicine, St. Paul, Minnesota., O'Brien TD; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.; Animal Cancer Care and Research Program, University of Minnesota, St. Paul, Minnesota.; Department of Veterinary Population Medicine, University of Minnesota College of Veterinary Medicine, St. Paul, Minnesota.; Stem Cell Institute University of Minnesota, Minneapolis, Minnesota., Spector LG; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.; Department of Pediatrics, University of Minnesota School of Medicine, Minneapolis, Minnesota., Largaespada DA; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.; Department of Pediatrics, University of Minnesota School of Medicine, Minneapolis, Minnesota.; Department of Genetics, Cell Biology and Development, University of Minnesota School of Medicine, Minneapolis, Minnesota.; Brain Tumor Program, University of Minnesota, Minneapolis, Minnesota.; Center for Genome Engineering, University of Minnesota, Minneapolis, Minnesota., Modiano JF; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.; Animal Cancer Care and Research Program, University of Minnesota, St. Paul, Minnesota.; Department of Veterinary Clinical Sciences, University of Minnesota College of Veterinary Medicine, St. Paul, Minnesota.; Stem Cell Institute University of Minnesota, Minneapolis, Minnesota.; Department of Laboratory Medicine and Pathology, University of Minnesota School of Medicine, Minneapolis, Minnesota.; Center for Immunology, University of Minnesota, Minneapolis, Minnesota., Subramanian S; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.; Department of Surgery, University of Minnesota School of Medicine, Minneapolis, Minnesota., Sarver AL; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota. sarver@umn.edu.; Institute for Health Informatics, University of Minnesota, Minneapolis, Minnesota.
Jazyk:	angličtina
Zdroj:	Cancer research [Cancer Res] 2018 Jan 15; Vol. 78 (2), pp. 326-337. Date of Electronic Publication: 2017 Oct 24.
DOI:	10.1158/0008-5472.CAN-17-0576
Abstrakt:	Overall survival of patients with osteosarcoma (OS) has improved little in the past three decades, and better models for study are needed. OS is common in large dog breeds and is genetically inducible in mice, making the disease ideal for comparative genomic analyses across species. Understanding the level of conservation of intertumor transcriptional variation across species and how it is associated with progression to metastasis will enable us to more efficiently develop effective strategies to manage OS and to improve therapy. In this study, transcriptional profiles of OS tumors and cell lines derived from humans ( n = 49), mice ( n = 103), and dogs ( n = 34) were generated using RNA sequencing. Conserved intertumor transcriptional variation was present in tumor sets from all three species and comprised gene clusters associated with cell cycle and mitosis and with the presence or absence of immune cells. Further, we developed a novel gene cluster expression summary score (GCESS) to quantify intertumor transcriptional variation and demonstrated that these GCESS values associated with patient outcome. Human OS tumors with GCESS values suggesting decreased immune cell presence were associated with metastasis and poor survival. We validated these results in an independent human OS tumor cohort and in 15 different tumor data sets obtained from The Cancer Genome Atlas. Our results suggest that quantification of immune cell absence and tumor cell proliferation may better inform therapeutic decisions and improve overall survival for OS patients. Significance: This study offers new tools to quantify tumor heterogeneity in osteosarcoma, identifying potentially useful prognostic biomarkers for metastatic progression and survival in patients. Cancer Res; 78(2); 326-37. ©2017 AACR . (©2017 American Association for Cancer Research.)
Databáze:	MEDLINE
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