Sdps-29 serum-derived cd47 as a marker of tumor burdenand outcome in gbm patients – correlative analysisof tumor location, radiation therapy volumes,and survival

Abstract Glioblastomas (GBM) are the most aggressive central nervous system tumors exhibiting near universal recurrence following resection and chemoradiation (CRT). CD47 is an integrin-associated transmembrane protein associated with immunomodulation, invasion, and stemness that is highly expressed in GBM. We tested the hypothesis patient serum-derived CD47 measured pre vs. post-CRT may be related to tumor burden by exploring its association with tumor dissemination in the brain, RT volumes, and outcomes. CD47 was analyzed using an aptamer-based SOMAscan proteomic assay on serum collected pre and post CRT for 82 individuals with a pathologic diagnosis of GBM. Clinical features (tumor location (cortical/periventricular), gross tumor volumes (GTVT1, GTVT2), and outcome (overall survival (OS), progression-free survival (PFS)) were analyzed in conjunction with alteration in CD47 levels. Alteration in CD47 level was associated with OS (HR = 32.34 CI: 3.520 - 288.3, p = 0.0004053) and PFS (HR =8.5, p = .0008 CI: 0.2291-4.011). Expression of CD47 increased after CRT (p = .022). Patients with periventricular tumors had higher expression of CD47 pre vs. post CRT (p = 0.0188) and worse OS (median 13 vs. 25 months) and PFS (median 5 vs. 10 months) as compared to patients with strictly cortical tumor presence. A positive correlation was identified between GTVT1 and GTVT2 and CD47 expression levels (p = .0006). Lower CD47 expression values were associated with higher survival probability (p = .013). The stratification of CD47 expression levels yielded increasingly significant results with the separation of discrete survival groups (p = .00013), indicating clinically distinct subtypes of GBM. Tumor location (cortical vs. periventricular) and GTVT1 correlated with OS and PFS (p<0.05), unlike GTVT2 in this cohort in the absence of CD47 expression level. CD47 expression levels correlate with tumor location, RT volumes, OS, and PFS with distinct GBM subtypes potentially stratified via serum CD47 expression levels.