Association between CD47 expression, clinical characteristics and prognosis in patients with advanced non-small cell lung cancer

Abstract

Objective: CD47 is an antiphagocytic molecule that contributes to tumor cell resistance in host immune surveillance. CD47 overexpression correlated with tumor progression and shorter survival in lung cancer. However, the expression and functional significance of CD47 in Non-Small Cell Lung Cancer (NSCLC) has not been completely understood.

Materials and methods: In this retrospective study, CD47 expression was immunohistochemically examined in tumor biopsies from 169 NSCLC patients. The association of CD47 levels (H-score) with clinicopathological characteristics and survival outcomes was evaluated.

Results: CD47 protein was detected in 84% of patients with a median expression of 80% (0-100). Tumor CD47 levels above 1% and 50% were found in 84% and 65.7% of patients, respectively. While, median CD47 staining index was 160 (0-300). Patients were divided into two groups according to CD47 expression (high or low), using a cutoff value of 150. High CD47 expression was associated with wood smoke exposure (71.1% vs 28.9%, P = .013) and presence of EGFR (+) mutations (66.7% vs 33.3%, P = .04). Survival analysis carried out in the whole population did not show any association of CD47 expression and survival outcome. However, in patients with EGFR (+) mutations, CD47 expression was associated with higher progression-free survival (PFS) (12.2 vs. 4.4 months, P = .032). When the survival analysis was performed according to CD47 levels (cut off value: 150), both, PFS and overall survival (OS) were shortened in patients with a high expression of CD47 (10.7 vs. NR, P = .156) and (29.2 vs. NR months P = .023), respectively.

Conclusions: CD47 overexpression is not a prognostic factor for PFS and OS in NSCLC patients. However, the presence of EGFR mutations and high expression of CD47 were associated with shortened PFS and OS. Coexpression of these markers represents a potential biomarker and characterizes a therapeutic niche for lung cancer.

Keywords: CD47; EGFR; immune checkpoint; lung adenocarcinoma; phagocytosis.

Figure 1

CD47 expression in NSCLC patients. A, Representative immunohistochemical staining of CD47 (brown signal) from human NSCLC biopsies showing the score system used. Magnification, x 400. Staining index of CD47. B, Median intensity, percentage of expression and score of CD47

Figure 2

Kaplan‐Meier curves of PFS and EGFR mutational status. A and B, Kaplan‐Meier curves of PFS stratified according to EGFR‐WT and CD47 presence or expression level (cut‐off point 150). C, Curves of PFS stratified according to EGFR (+) and CD47 expression level

Figure 3

Kaplan‐Meier curves for OS in all patients (A) OS curves according to CD47 presence (B) OS curves according to CD47 levels in all patients (C) OS curves for EGFRwt in CD47 absence or presence and (D) high or low CD‐47 expression. (E) Patients with or without EGFR mutations and (F) CD47 expression higher or lower than 150. CEA, Carcinoembryonic antigen; CI, Confidence interval; CNS, Central Nervous System; ECOG PS, Eastern cooperative oncology group performance status; EGFR, Epidermal Growth Factor; NR, Not reach; NC, Not calculated; TKI, Tyrosine kinase inhibitors