Immune Gene and Cell Enrichment Is Associated with a Good Prognosis in Ependymoma

Abstract

Approximately 50% of children with ependymoma will suffer from tumor recurrences that will ultimately lead to death. Development of more effective therapies and patient stratification in ependymoma mandates better prognostication. In this study, tumor gene expression microarray profiles from pediatric ependymoma clinical samples were subject to ontological analyses to identify outcome-associated biological factors. Histology was subsequently used to evaluate the results of ontological analyses. Ontology analyses revealed that genes associated with nonrecurrent ependymoma were predominantly immune function-related. Additionally, increased expression of immune-related genes was correlated with longer time to progression in recurrent ependymoma. Of those genes associated with both the nonrecurrent phenotype and that positively correlated with time to progression, 95% were associated with immune function. Histological analysis of a subset of these immune function genes revealed that their expression was restricted to a subpopulation of tumor-infiltrating cells. Analysis of tumor-infiltrating immune cells showed increased infiltration of CD4+ T cells in the nonrecurrent ependymomas. No genomic sequences for SV40, BK, JC, or Merkel polyomaviruses were found in nonrecurrent ependymoma. This study reveals that up-regulation of immune function genes is the predominant ontology associated with a good prognosis in ependymoma and it provides preliminary evidence of a beneficial host proinflammatory and/or Ag-specific immune response.

The Genomic Landscape of Pancreatic and Periampullary Adenocarcinoma

“…RAB12 is a Ras oncogene family member and is overexpressed in colorectal cancers (44). Furthermore, the COLEC12 gene is known prognostic marker in anaplastic thyroid cancer and brain tumors (45,46). Because of limited clinical annotation of the TCGA data, we were unable to validate these as prognostic markers in the TCGA cohort.…”

A prognostic gene expression signature in infratentorial ependymoma

“…Apart from histological grade and incomplete resection, several prognostic markers have been studied in ependymomas including Ki-67 [3], survivin [1], human telomerase reverse transcriptase, ERBB family members [11] and nucleolin [30]. Whole genome approaches such as array comparative genomic hybridization [20; 24; 28] and gene expression profiling [8; 16; 25; 27; 34] have also been employed for the identification of prognostic biomarkers. However, despite these studies molecular markers for disease prognosis have not been integrated into the clinical management of ependymomas.…”

Dual roles for immune metagenes in breast cancer prognosis and therapy prediction

“…Often revealed by hierarchical clustering techniques or outcome correlation studies, these signatures distinguish multiple different immune cell types [32][33][34][35][36][37] and recapitulate immunohistochemistry-based observations in breast cancer that link tumor-infiltrating immune cell abundance to disease-free survival and overall survival of patients [30,[36][37][38][39][40][41][42]. More recently, similar studies involving presurgical breast tumor biopsies have begun to demonstrate associations between immunity-related genes and tumor responsiveness to neoadjuvant chemotherapy [22,44,45,63,64].…”

“…Indeed, the mere abundance of tumor-infiltrating leukocytes, namely CD3+/CD8+ T lymphocytes, has been robustly correlated with pCR in the neoadjuvant setting [22][23][24][25] as well as relapse-free and overall survival of breast cancer patients [25][26][27][28][29]. In more recent years, microarray expression profiling studies in breast and other tumor types have identified immune gene signatures from whole tumor RNA extracts that reflect the abundance of tumor-infiltrating immune cells [30][31][32][33][34][35][36][37][38]. We and others have found that the biological and phenotypic properties of the genes comprising these signatures implicate distinct immune cell lineages [34][35][36][37]39,40], and that combinations of these immune genes correlate with patient outcomes ranging from recurrence-free survival [30,32,[36][37][38][39][40][41][42][43] to tumor regression in the neoadjuvant setting [44][45][46][47].…”