Radiogenomics Profiling for Glioblastoma-related Immune Cells Reveals CD49d Expression Correlation with MRI parameters and Prognosis

Hye Rim Cho,Hyejin Jeon,Chul-Kee Park,Seung Hong Choi,Sung-Hye Park

doi:10.1038/s41598-018-34242-9

Abstract

Although there have been a plethora of radiogenomics studies related to glioblastoma (GBM), most of them only used genomic information from tumor cells. In this study, we used radiogenomics profiling to identify MRI-associated immune cell markers in GBM, which was also correlated with prognosis. Expression levels of immune cell markers were correlated with quantitative MRI parameters in a total of 60 GBM patients. Fourteen immune cell markers (i.e., CD11b, CD68, CSF1R, CD163, CD33, CD123, CD83, CD63, CD49d and CD117 for myeloid cells, and CD4, CD3e, CD25 and CD8 for lymphoid cells) were selected for RNA-level analysis using quantitative RT-PCR. For MRI analysis, quantitative MRI parameters from FLAIR, contrast-enhanced (CE) T1WI, dynamic susceptibility contrast perfusion MRI and diffusion-weighted images were used. In addition, PFS associated with interesting mRNA data was performed by Kaplan-Meier survival analysis. CD163, which marks tumor associated microglia/macrophages (TAMs), showed the highest expression level in GBM patients. CD68 (TAMs), CSF1R (TAMs), CD33 (myeloid-derived suppressor cell) and CD4 (helper T cell, regulatory T cell) levels were highly positively correlated with nCBV values, while CD3e (helper T cell, cytotoxic T cell) and CD49d showed a significantly negative correlation with apparent diffusion coefficient (ADC) values. Moreover, regardless of any other molecular characteristics, CD49d was revealed as one independent factor for PFS of GBM patients by Cox proportional-hazards regression analysis (P = 0.0002). CD49d expression level CD49d correlated with ADC can be considered as a candidate biomarker to predict progression of GBM patients.

Highlights

We found significant negative correlations between the expression levels of CD49d and CD3e and apparent diffusion coefficient (ADC) values from both FLAIR and CE T1-weighted imaging (T1WI), and those of CD33 and CD123, and CD25 were negatively correlated with ADC values from FLAIR and CE T1WI, respectively (Fig. 2B; Case 3 and 4)
We applied radiogenomics profiling to the association between quantitative MRI features and expression levels of immune cell markers in GBM patients, which was correlated with progression-free survival (PFS)
In terms of CBV values based on FLAIR or CE T1WI, the expression levels of CD68, CSF1R, CD33, CD4 and CD11b showed positive correlations

Summary

Introduction

The main feature of the M2 type is anti-inflammation, which correlates with the pro-tumorigenic function in TME. They are known as tumor associated microglia/ macrophages (TAMs), whose presence in tumors supports angiogenesis and invasion[9,10,11,12,13]. Radiogenomics is the study linking medical images with the genomic profiles of human tumors. It has several benefits in terms of providing opportunities for non-invasive diagnostics and prognostics. We used radiogenomics profiling to identify MRI-associated immune cell markers in GBM, which was correlated with prognosis

Methods

Results

Conclusion