Combination of CD47 and CD68 expression predicts survival in eastern-Asian patients with non-small cell lung cancer

J Cancer Res Clin Oncol. 2021 Mar;147(3):739-747. doi: 10.1007/s00432-020-03477-3. Epub 2021 Jan 4.

Abstract

Objective: Recent studies have indicated that CD47, interacting with SIRP-α, conveys "don't eat me" signal in evasion of tumor cells and serves as a potential target for cancer immunotherapy. The purpose of this study was to investigate the clinical correlation of CD47 and uncover prognostic implications of CD47 and CD68 in non-small cell lung cancer (NSCLC).

Methods: The specimens from 384 patients with completely resected NSCLC were collected for immunohistochemical assays of CD47 and CD68. Cox multivariate proportion hazard analyses were conducted to confirm the independent prognostic value of CD47 and CD68. TCGA database and GSE37745 were used to identify the association between CD47 and immune cells.

Results: In 186 pairs of lung cancer and adjacent tissues, the RNA of CD47 was overexpressed in lung cancer tissues (P < 0.001). High expression of CD47 was associated with worse recurrence-free survival in RNA and protein level (P = 0.032 and P < 0.001, respectively). High expression of CD47 was significantly associated with large tumor size (P = 0.004), advanced pathologic TNM stage (P < 0.001), and histology (P = 0.003). Further analyses demonstrated that CD47 and CD68 predicted outcomes of patients independently. In addition, the expression of CD47 correlated with neutrophils, and did not correlated with B cells and CD4 + T cells in the TCGA database and GSE37745.

Conclusion: Combined use of CD47 and CD68 exhibited excellent performance in predicting survival of patients with NSCLC. CD47 was a potential therapeutic target for immune therapy of lung cancer.

Keywords: Immune cell infiltration; Immunohistochemical assays; Non-small cell lung cancer; Prognostic analyses.

MeSH terms

  • Aged
  • Antigens, CD / biosynthesis*
  • Antigens, CD / genetics
  • Antigens, CD / immunology
  • Antigens, Differentiation, Myelomonocytic / biosynthesis*
  • Antigens, Differentiation, Myelomonocytic / genetics
  • Antigens, Differentiation, Myelomonocytic / immunology
  • Asia / epidemiology
  • CD47 Antigen / biosynthesis*
  • CD47 Antigen / genetics
  • CD47 Antigen / immunology
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / immunology
  • Carcinoma, Non-Small-Cell Lung / mortality*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cohort Studies
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Lung Neoplasms / genetics
  • Lung Neoplasms / immunology
  • Lung Neoplasms / mortality*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • RNA / genetics
  • RNA / metabolism

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD47 Antigen
  • CD47 protein, human
  • CD68 antigen, human
  • RNA