title: A signature of immune function genes associated with recurrence-free survival in breast cancer patients.
abstract: The clinical significance of tumor-infiltrating immune cells has been reported in a variety of human carcinomas including breast cancer. However, molecular signature of tumor-infiltrating immune cells and their prognostic value in breast cancer patients remain elusive. We hypothesized that a distinct network of immune function genes at the tumor site can predict a low risk versus high risk of distant relapse in breast cancer patients regardless of the status of ER, PR, or HER-2/neu in their tumors. We conducted retrospective studies in a diverse cohort of breast cancer patients with a 1-5 year tumor relapse versus those with up to 7 years relapse-free survival. The RNAs were extracted from the frozen tumor specimens at the time of diagnosis and subjected to microarray analysis and real-time RT-PCR. Paraffin-embedded tissues were also subjected to immunohistochemistry staining. We determined that a network of immune function genes involved in B cell development, interferon signaling associated with allograft rejection and autoimmune reaction, antigen presentation pathway, and cross talk between adaptive and innate immune responses were exclusively upregulated in patients with relapse-free survival. Among the 299 genes, five genes which included B cell response genes were found to predict with >85% accuracy relapse-free survival. Real-time RT-PCR confirmed the 5-gene prognostic signature that was distinct from an FDA-cleared 70-gene signature of MammaPrint panel and from the Oncotype DX recurrence score assay panel. These data suggest that neoadjuvant immunotherapy in patients with high risk of relapse may reduce tumor recurrence by inducing the immune function genes.
authors.affiliation: Infectious Disease and Immunogenetics Section (IDIS), Department of Transfusion Medicine and Center for Human Immunology, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Maria Libera
authors.initials: ML
authors.lastname: Ascierto
authors.forename: Maciej
authors.initials: M
authors.lastname: Kmieciak
authors.forename: Michael O
authors.initials: MO
authors.lastname: Idowu
authors.forename: Rose
authors.initials: R
authors.lastname: Manjili
authors.forename: Yingdong
authors.initials: Y
authors.lastname: Zhao
authors.forename: Margaret
authors.initials: M
authors.lastname: Grimes
authors.forename: Catherine
authors.initials: C
authors.lastname: Dumur
authors.forename: Ena
authors.initials: E
authors.lastname: Wang
authors.forename: Viswanathan
authors.initials: V
authors.lastname: Ramakrishnan
authors.forename: Xiang-Yang
authors.initials: XY
authors.lastname: Wang
authors.forename: Harry D
authors.initials: HD
authors.lastname: Bear
authors.forename: Francesco M
authors.initials: FM
authors.lastname: Marincola
authors.forename: Masoud H
authors.initials: MH
authors.lastname: Manjili
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000401:mortality; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D011379:Prognosis; D012008:Recurrence; D015398:Signal Transduction; D059016:Tumor Microenvironment / Q000235:genetics / Q000276:immunology
chemical_list: D014408:Biomarkers, Tumor