CD47 expression in gastric cancer clinical correlates and association with macrophage infiltration

Shi, Meng; Gu, Yun; Jin, Kaifeng; Fang, Hanji; Chen, Yifan; Cao, Yifan; Liu, Xin; Lv, Kunpeng; He, Xingkang; Lin, Chao; Liu, Hao; He, Li; He, Hongyong; Qin, Jing; Li, Ruochen; Zhang, Heng; Zhang, Weijuan

doi:10.1007/s00262-020-02806-2

Cited by 49 publications

(40 citation statements)

References 44 publications

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“…It is suggested that THBS1 may be involved in the mechanism of M2 macrophage-mediated tumorigenesis and thus differentiation into TAMs. THBS1 binding to CD36 and CD47 receptors can play different roles in TME, and THBS1 interacts with CD47 on immune cells, thus inactivating anti-tumor immune surveillance, which may attenuate the anti-tumor effect of M1 polarized macrophages in GC 31 and CD36 could promote the activation of M2 macrophages and also promote the migration and recruitment of TAMs in tumor tissues, thus promoting the progression of tumor. 32 Therefore, we speculate that THBS1 may be involved in the mechanism of M2 macrophages and TAMs-mediated tumorigenesis through binding to CD36, to be proven by subsequent studies.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of THBS1 is Related to Immunity and Chemotherapy Resistance in Gastric Cancer

Zhang¹,

Huang²,

Li³

et al. 2021

IJGM

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Purpose Thrombospondin 1 ( THBS1 ) is an endogenous inhibitor of angiogenesis, but it also promotes tumor invasion, metastasis, and immune response in the tumor environment. Previous research has found that THBS1 is highly expressed in many tumors and has a negative correlation with tumor prognosis. However, research on the relationship between THBS1 and immune infiltration in GC is less well documented, and the objective of our study was to investigate the role of THBS1 expression in GC. Patients and Methods The expression of THBS1 in GC was analyzed by Oncomine, TIMER, TGCA, GEO and IHC staining. Analysis of the signaling pathways associated with THBS1 expression in GC uses GSEA. The relationship between THBS1 expression and immune infiltration was analyzed by the ESTIMATE algorithm, single-cell transcriptome analysis, TIMER2 database and CIBERSORT algorithm. Finally, the relationship between THBS1 expression and drug sensitivity was analyzed by the CellMiner database. Results THBS1 was overexpressed in GC and was associated with poor prognosis, and high THBS1 expression was an independent risk factor. GSEA results showed that high THBS1 expression in GC was associated with tumorigenesis, adhesion, and significant immune enrichment. THBS1 expression was most strongly correlated with tumor-associated macrophages (TAMs), M2 macrophages and cancer-associated fibroblast (CAFs) in GC. THBS1 expression positively correlates with most immune checkpoint members, suggesting that THBS1 may play an important role in the tumor microenvironment. THBS1 overexpression was negatively correlated with some drug sensitivities, such as Oxaliplatin. Conclusion Upregulation of THBS1 was positively correlated with poor prognosis and immunosuppression in GC and negatively correlated with anticancer drug sensitivity, suggesting that THBS1 may serve as a potential target for the treatment of GC.

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Section: Discussionmentioning

confidence: 99%

Upregulation of THBS1 is Related to Immunity and Chemotherapy Resistance in Gastric Cancer

Zhang¹,

Huang²,

Li³

et al. 2021

IJGM

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“…In addition to the CD47-SIRPα signaling pathway, significance of CD47 expression has been investigated in different malignancies. Association between CD47 expression, clinical characteristics and prognosis in patients with different malignancies, including advanced non-small cell lung cancer [ 1 ], gastric cancer [ 2 ], colorectal adenocarcinoma [ 3 ] and pancreatic neuroendocrine tumor [ 4 ] has been explored. For example, in patients with high-grade lung neuroendocrine tumors, the high expression of CD47 was strongly associated with a worse progression-free survival, especially in patients with a Ki-67 > 40% [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

Targeting CD47 for cancer immunotherapy

et al. 2021

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Much progress has been made in targeting CD47 for cancer immunotherapy in solid tumors (ST) and hematological malignancies. We summarized the CD47-related clinical research and analyzed the research trend both in the USA and in China. As of August 28, 2021, there are a total 23 related therapeutic agents with 46 clinical trials in the NCT registry platform. Among these trials, 29 are in ST, 14 in hematological malignancies and 3 in both solid tumor and hematological malignancy. The ST include gastric cancer, head and neck squamous cell carcinoma and leiomyosarcoma, while the hematological malignancies include non-Hodgkin's lymphoma, acute myeloid leukemia, myelodysplastic syndrome, multiple myeloma and chronic myeloid leukemia. Majority of the CD47-related clinical trials are at the early phases, such as 31 at phase I, 14 at phase II and 1 at phase III in the USA and 9, 6, 1, in China, respectively. The targets and spectrums of mechanism of action include 26 with mono-specific and 20 with bi-specific targets in the USA and 13 with mono-specific and 3 with bi-specific targets in China. The new generation CD47 antibodies have demonstrated promising results, and it is highly hopeful that some candidate agents will emerge and make into clinical application to meet the urgent needs of patients.

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“…Therefore, it is generally accepted in the clinic that if a tumor does not relapse within 5 years after surgery, the probability of recurrence is very low and negligible. Shi et al [22] . showed that high CD47 expression was positively correlated with TNM stage, the incidence of distant metastasis, and the mortality rate of melanoma patients and that high CD47 expression was an independent prognostic indicator of overall survival and progression-free survival in GC patients.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Significance of CKS2 and CD47 Expression in Patients With Gastric Cancer Who Underwent Radical Gastrectomy

Y¹,

Zeng²,

Zhuang³

et al. 2021

Preprint

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Objective: To investigate the protein expression levels of cyclin‑dependent kinase subunit 2 (CKS2) and cluster of differentiation (CD) 47 in gastric cancer (GC) and their clinical significances. Methods: A total of 126 GC patients who underwent radical resection were selected as study subjects. Additionally, 32 patients with benign gastric tumor, 42 patients with low-grade intraepithelial neoplasia (LGIEN), and 49 patients with high-grade intraepithelial neoplasia (HGIEN) who underwent surgery were selected as the control groups. Immunohistochemistry was used to detect the expression of CKS2 and CD47 in surgical specimens. We statistically analyzed the clinical significance of the expression of the two factors. Results: (1) The positivity rates for CKS2 in benign gastric tumor tissue, LGIEN tissue, HGIEN tissue, and GC tissue gradually increased, i.e., 6.3% (2/32), 30.9% (13/42), 38.8% (19/49), and 60.3% (76/126), respectively, and the positivity rates for CD47 were 18.8% (6/32), 38.1% (16/42), 46.9% (23/49), and 65.9% (83/126), respectively. (2) High expression of CKS2 and CD47 were associated with tumor diameter, Lauren classification, number of lymph node metastases, and TNM stage. In addition, the immunohistochemical scores for CKS2 and CD47 were positively correlated (r=0.625, P=0.000). (3) The median follow-up time of 126 patients was 46.5 months, and the overall survival rate was 40.5% (51/126). Survival analysis showed that compared with that in the CKS2 (-) group, the overall survival rate for patients in the CKS2 (+) group was significantly worse (25.0% vs 64.0%, 2=15.67, P=0.000) and that compared with the CD47 (-) group, the CD47 (+) group had significantly worse overall survival (30.1% vs 60.5%, 2=15.67, P=0.000). (4) The overall survival rates of CKS2(+)CD47(+) group, CKS2(+)CD47(-) group, CKS2(-)CD47(+) group, and CKS2 (-)CD47 (-) group were 20.0%(13/65), 58.3%(7/12), 57.1%(8/14), 65.7% (23/35), respectively, the prognosis of patients in CKS2(+)CD47(+) group was significantly poor. Conclusion: High expression levels of CKS2 and CD47 were closely related to the occurrence of GC and can be used as independent risk factors to assess the prognosis of patients.

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CD47 expression in gastric cancer clinical correlates and association with macrophage infiltration

Cited by 49 publications

References 44 publications

Upregulation of THBS1 is Related to Immunity and Chemotherapy Resistance in Gastric Cancer

Upregulation of THBS1 is Related to Immunity and Chemotherapy Resistance in Gastric Cancer

Targeting CD47 for cancer immunotherapy

Prognostic Significance of CKS2 and CD47 Expression in Patients With Gastric Cancer Who Underwent Radical Gastrectomy

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