CD47 and IFT57 Are Colinear Genes That Are Highly Coexpressed in Most Cancers and Exhibit Parallel Cancer-Specific Correlations with Survival

Sep 21, 2026

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High CD47 expression is often linked to poor cancer survival, consistent with its role in blocking phagocytic clearance by engaging an inhibitory counter-receptor on innate immune cells. Yet CD47 mRNA correlates inconsistently with survival across cancers. IFT57, a key primary cilium component colinear with CD47 in amniote genomes, emerges as a major coexpressed partner in TCGA datasets across 1156 cancer cell lines and most tumor types. Parallel survival correlations are observed for IFT57 and CD47 in thyroid and lung carcinomas, melanoma, and glioma. In papillary thyroid carcinoma, CD47–IFT57 coexpression associates with significantly improved overall survival. IFT57 knockdown in thyroid carcinoma cells identifies CRACD as a specific IFT57 target, and inverse CRACD expression links to reduced survival in low-grade gliomas, lung adenocarcinomas, and papillary thyroid carcinomas, indicating IFT57-driven survival regulation in these contexts.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages20

Reading Time50 min

AccessFree to download

Introduction

CD47 expression and survival associations

Immune-checkpoint interpretation and exceptions

Alternative hypothesis: IFT57 coexpression and primary cilium regulation

Study rationale and downstream targets

Article CD47 and IFT57 Are Colinear Genes That Are Highly Coexpressed in Most Cancers and Exhibit Parallel Cancer-Specific Correlations with Survival Kun Dong 1, Raghib Nihal 1, Thomas J. Meyer 2, Satya P. Singh 3, Sukhbir Kaur 1,* and David D. Roberts 1, * Citation: Dong, K.; Nihal, R.; Meyer, T.J.; Singh, S.P.; Kaur, S.; Roberts, D.D. CD47 and IFT57 Are Colinear Genes That Are Highly Coexpressed in Most Cancers and Exhibit Parallel Cancer-Specific Correlations with Survival. Int. J. Mol. Sci. 2024, 25, 8956 . [https://doi.org/10.3390/ijms25168956](https://doi.org/10.3390/ijms25168956) Academic Editor: Seth Frietze Received: 17 July 2024 Revised: 9 August 2024 Accepted: 14 August 2024 Published: 17 August 2024 Copyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA; [kun.dong@fda.hhs.gov](kun.dong@fda.hhs.gov) (K.D.); [nihalra@vcu.edu](nihalra@vcu.edu) (R.N.) 2 CCR Collaborative Bioinformatics, Resource, Office of Science and Technology Resources, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA; [thomas.meyer@nih.gov](thomas.meyer@nih.gov) 3 Inflammation Biology Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; [spsingh@niaid.nih.gov](spsingh@niaid.nih.gov) * Correspondence: [sukhbir.kaur@nih.gov](sukhbir.kaur@nih.gov) (S.K.); [droberts@mail.nih.gov](droberts@mail.nih.gov) (D.D.R.) Abstract: An association between high CD47 expression and poor cancer survival has been attributed to its function on malignant cells to inhibit phagocytic clearance. However, CD47 mRNA expression in some cancers lacks correlation or correlates with improved survival. IFT57 encodes an essential primary cilium component and is colinear with CD47 across amniote genomes, suggesting coregulation of these genes. Analysis of The Cancer Genome Atlas datasets identified IFT57 as a top coexpressed gene with CD47 among 1156 human cancer cell lines and in most tumor types. The primary cilium also regulates cancer pathogenesis, and correlations between IFT57 mRNA and survival paralleled those for CD47 in thyroid and lung carcinomas, melanoma, and glioma. CD47 ranked first for coexpression with IFT57 mRNA in papillary thyroid carcinomas, and higher expression of both genes correlated with significantly improved overall survival. CD47 and IFT57 mRNAs were coordinately regulated in thyroid carcinoma cell lines. Transcriptome analysis following knockdown of CD47 or IFT57 in thyroid carcinoma cells identified the cytoskeletal regulator CRACD as a specific target of IFT57 . CRACD mRNA expression inversely correlated with IFT57 mRNA and with survival in low-grade gliomas, lung adenocarcinomas, and papillary thyroid carcinomas, suggesting that IFT57 rather than CD47 regulates survival in these cancers. Keywords: lung adenocarcinoma; glioma; papillary thyroid carcinoma; primary cilium; CD47; intraflagellar transport-57 (IFT57); RNA sequencing; microsynteny; capping protein inhibiting regulator of actin dynamics (CRACD) 1. Introduction The expression of the cell surface glycoprotein CD47 is elevated in many solid tumorsand hematologic malignancies [1,2] . Higher CD47 expression in some cancers correlates with decreased patient survival [3–6] . The prevailing evidence indicates that high CD47 expression on the surface of cancer cells functions in those cancers as an immune checkpoint by engaging its inhibitory counter-receptor, signal regulatory protein-α, on innate i

FAQs

Why is CD47 expression commonly associated with poor cancer survival?

High CD47 on malignant cells is thought to inhibit immune clearance by functioning as an immune checkpoint that engages inhibitory signaling pathways in innate immune cells, limiting tumor elimination.

What evidence supports IFT57 as a coexpressed gene with CD47 across cancers?

Analysis of TCGA datasets showed IFT57 as one of the top genes coexpressed with CD47 among 1156 human cancer cell lines across most tumor types.

How does the study connect IFT57 to survival through CRACD?

Transcriptome analysis after knocking down CD47 or IFT57 in thyroid carcinoma cells identified CRACD as a specific target of IFT57. CRACD mRNA expression inversely correlated with IFT57 mRNA and survival in multiple cancer types, suggesting IFT57 regulates survival in these contexts.

Sep 21, 2026

Uploaded by Ezra