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.
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Abbreviations
- CI:
-
Confidential interval
- HR:
-
Hazard ratio
- ICIs:
-
Immune-checkpoint inhibitors
- IHC:
-
Immunohistochemistry
- IRS:
-
Immunoreactivity score
- LUAD:
-
Lung adenocarcinoma
- LUSC:
-
Lung squamous carcinoma
- NSCLC:
-
Non-small-cell lung cancer
- OS:
-
Overall survival
- RFS:
-
Recurrence-free survival
- TAMs:
-
Tumor-associated macrophages
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Funding
This work was supported by the National Natural Science Foundation of China (81930073 and 81772466), Shanghai Municipal Science and Technology Major Project (Grant No. 2017SHZDZX01, VBH1323001/026), Shanghai Municipal Key Clinical Specialty Project (SHSLCZDZK02104), and Pilot Project of Fudan University (IDF159034).
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Supplementary Figure 1. The association between CD47 and CD68 in the TCGA database (A) and our cohort (B). Spearman’s tests were carried out to investigate the correlation between CD47 and CD68.
Supplementary Figure 2. The correlation between CD47 and infiltration of immune cells from innate (A) and adaptive (B) immune system in GSE37745.
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Fu, F., Zhang, Y., Gao, Z. et al. Combination of CD47 and CD68 expression predicts survival in eastern-Asian patients with non-small cell lung cancer. J Cancer Res Clin Oncol 147, 739–747 (2021). https://doi.org/10.1007/s00432-020-03477-3
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DOI: https://doi.org/10.1007/s00432-020-03477-3