Deconvolution of the Gene Expression Profiles of Valuable Banked Blood Specimens for Studying the Prognostic Values of Altered Peripheral Immune Cell Proportions in Cancer Patients

BACKGROUND The altered composition of immune cells in peripheral blood has been reported to be associated with cancer patient survival. However, analysis of the composition of peripheral immune cells are often limited in retrospective survival studies employing banked blood specimens with long-term follow-up because the application of flow cytometry to such specimens is problematic. The aim of this study was to demonstrate the feasibility of deconvolving blood-based gene expression profiles (GEPs) to estimate the proportions of immune cells and determine their prognostic values for cancer patients. METHODS AND RESULTS Here, using GEPs from peripheral blood mononuclear cells (PBMC) of 108 non-small cell lung cancer (NSCLC) patients, we deconvolved the immune cell proportions and analyzed their association with patient survival. Univariate Kaplan-Meier analysis showed that a low proportion of T cells was significantly associated with poor patient survival, as was the proportion of T helper cells; however, only the proportion of T cells was independently prognostic for patients by a multivariate Cox regression analysis (hazard ratio = 2.23; 95% CI, 1.01-4.92; p = .048). Considering that altered peripheral blood compositions can reflect altered immune responses within the tumor microenvironment, based on a tissue-based GEPs of NSCLC patients, we demonstrated a significant association between poor patient survival and the low level of antigen presentation, which play a critical role in T cell proliferation. CONCLUSIONS These results demonstrate that it is feasible to deconvolve GEPs from banked blood specimens for retrospective survival analysis of alterations of immune cell composition, and suggest the proportion of T cells in PBMC which might reflect the antigen presentation level within the tumor microenvironment can be a prognostic marker for NSCLC patients.