Differential antigen expression profile predicts immunoreactive subset of advanced ovarian cancers.
The presence and composition of lymphocytes characterizing an immune response has been connected to prognosis in advanced ovarian cancer. Our aim is to establish novel associations between prognosis and the expression of immune-related genes through a focused screen utilizing publicly available high-throughput assays. We consider transcriptome profiles from n=1137 advanced ovarian cancer patients observed in four separate studies divided into discovery/validation sets (n=503/n=634). We focus on a subset of lymphocyte markers, antigen presentation and processing genes, T cell receptor associated co-stimulatory/repressor genes and cancer testis (CT) antigens. We modeled differential expression and co-expression using these subsets and tested for association with overall survival. Fifteen of 64 immune-related genes are associated with survival of which 5 are reproduced in the validation set. The expression of these genes defines an immunoreactive (IR) subgroup of patients with a favorable prognosis. Phenotypic characterization of the immune compartment signal includes upregulation of markers of CD8+ T-cell activation in these patients. Using multivariate model building, we find that the expression of 6 CT antigens can predict IR status in the discovery and validation sets. These analyses confirm that a genomic approach can reproducibly detect lymphocyte signals in tumor tissue suggesting a novel way to study the tumor microenvironment. Our search has identified new candidate prognostic markers associated with immune components and uncovered preliminary evidence of prognostic subgroups associated with different immune mechanisms.
Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, NY, United States of America.
Kevin H
KH
Eng
Center for Immunotherapy, Roswell Park Cancer Institute, Buffalo, NY, United States of America.
Takemasa
T
Tsuji
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D011379:Prognosis; D015203:Reproducibility of Results; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D059016:Tumor Microenvironment; D055815:Young Adult
D000951:Antigens, Neoplasm