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. 2024 Nov 5;12(11):e010326.
doi: 10.1136/jitc-2024-010326.

Role of CD47 gene expression in colorectal cancer: a comprehensive molecular profiling study

Hiroyuki Arai  1   2 , Nishant Gandhi  3 , Francesca Battaglin  1 , Jingyuan Wang  1 , Sandra Algaze  1 , Priya Jayachandran  1 , Shivani Soni  1 , Wu Zhang  1 , Yan Yang  4 , Joshua Millstein  4 , Jae Ho Lo  1 , Davendra Sohal  5 , Richard Goldberg  6 , Michael J Hall  7 , Aaron James Scott  8 , Jimmy J Hwang  9 , Emil Lou  10 , Benjamin A Weinberg  11 , John Marshall  11 , Sanjay Goel  12 , Joanne Xiu  3 , W Michael Korn  3 , Heinz-Josef Lenz  13
Affiliations

Role of CD47 gene expression in colorectal cancer: a comprehensive molecular profiling study

Hiroyuki Arai et al. J Immunother Cancer. .

Abstract

Background: In patients with colorectal cancer (CRC), the therapeutic effects of conventional immune checkpoint inhibitors targeting the adaptive immune system are largely limited to those with microsatellite instability-high tumors. Meanwhile, new immunotherapies targeting the innate immune system are attracting increasing attention. CD47 is a representative innate immune checkpoint involved in the evasion of tumor cell phagocytosis by macrophages. This large-scale study comprehensively examined the molecular significance of CD47 gene expression in CRC.

Methods: We analyzed the next-generation sequencing data of DNA and RNA from 14,287 CRC cases included in the data set of a commercial Clinical Laboratory Improvement Amendments-certified laboratory (Caris Life Sciences). The cases were divided into two groups based on the median value of CD47 gene expression levels. The molecular and immune profiles between the groups were compared, and the relationship between CD47 expression and survival outcomes was further examined.

Results: In CD47-high tumors, the proportion of consensus molecular subtypes 1 and 4 was significantly higher than in CD47-low tumors. The expression levels of damage-associated molecular pattern-related genes showed a positive correlation with CD47 expression levels. Major oncogenic pathways, such as mitogen-activated protein kinase, phosphoinositide 3-kinase, angiogenesis, and transforming growth factor beta, were significantly activated in CD47-high tumors. Additionally, the expression levels of a panel of adaptive immune checkpoint genes and estimates of immune cells constituting the tumor microenvironment (TME) were significantly higher in CD47-high tumors.

Conclusions: CD47 expression in CRC was associated with the activation of several oncogenic pathways and an immune-engaged TME. Our findings may provide valuable information for considering new therapeutic strategies targeting innate immune checkpoints in CRC.

Keywords: Colorectal Cancer; Immunotherapy.

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Conflict of interest statement

Competing interests: NG, JX, and WMK are employees of Caris Life Sciences. All remaining authors have declared no conflicts of interest.

Figures

Figure 1
Figure 1. (A) Next-generation sequencing-based profiling and (B) clustering of CMS subtypes compared between CD47-high and CD47-low tumors. In (A) only alterations with a significant difference in frequency are shown. CMS, consensus molecular subtype.
Figure 2
Figure 2. Correlation between CD47 expression and major oncogenic signaling pathways by comparing the composite z-scores of genes listed in online supplemental tale S1) between CD47-high and CD47-low tumors. EMT, epithelial mesenchymal transition; MAPK, mitogen-activated protein kinase; PI3K, phosphoinositide 3-kinase; TGF, transforming growth factor.
Figure 3
Figure 3. Comparison of immune-related gene expression between CD47-high and CD47-low tumors.
Figure 4
Figure 4. Comparison of immune and stromal cell populations between CD47-high and CD47-low tumors. NK, natural killer.
Figure 5
Figure 5. Association between CD47 expression and overall survival. Comparison between groups divided by the median CD47 expression level: (A) all patients, (B) patients treated with angiogenesis inhibitors, and (C) patients treated with ICIs. Comparison between the top quartile (Q4) and bottom quartile (Q1) of CD47 expression levels: (D) all patients, (E) patients treated with angiogenesis inhibitors, and (F) patients treated with ICIs. ICIs, immune checkpoint inhibitors; OS, overall survival.
See this image and copyright information in PMC

References

    1. Overman MJ, McDermott R, Leach JL, et al. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study. Lancet Oncol. 2017;18:1182–91. doi: 10.1016/S1470-2045(17)30422-9. - DOI - PMC - PubMed
    1. Lenz H-J, Van Cutsem E, Luisa Limon M, et al. First-Line Nivolumab Plus Low-Dose Ipilimumab for Microsatellite Instability-High/Mismatch Repair-Deficient Metastatic Colorectal Cancer: The Phase II CheckMate 142 Study. J Clin Oncol. 2022;40:161–70. doi: 10.1200/JCO.21.01015. - DOI - PubMed
    1. André T, Shiu K-K, Kim TW, et al. Pembrolizumab in Microsatellite-Instability-High Advanced Colorectal Cancer. N Engl J Med. 2020;383:2207–18. doi: 10.1056/NEJMoa2017699. - DOI - PubMed
    1. Antoniotti C, Rossini D, Pietrantonio F. Upfront FOLFOXIRI plus bevacizumab with or without atezolizumab in the treatment of patients with metastatic colorectal cancer (AtezoTRIBE): a multicentre, open-label, randomised, controlled, phase 2 trial. Lancet Oncol. 2022;23:876–87. doi: 10.1016/S1470-2045(22)00274-1. - DOI - PubMed
    1. Lenz H-J, Parikh AR, Spigel DR, et al. Nivolumab (NIVO) + 5-fluorouracil/leucovorin/oxaliplatin (mFOLFOX6)/bevacizumab (BEV) versus mFOLFOX6/BEV for first-line (1L) treatment of metastatic colorectal cancer (mCRC): Phase 2 results from CheckMate 9X8. J C O. 2022;40:8. doi: 10.1200/JCO.2022.40.4_suppl.008. - DOI