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Short Article

The developmental gene Chordin is amplified and expressed in human cancers

ORCID Icon & ORCID Icon
Article: 2218147 | Received 26 Jan 2023, Accepted 19 May 2023, Published online: 29 May 2023
 

ABSTRACT

Chordin (CHRD) is a secreted protein important in early development, yet a role for CHRD in human disease has not been identified. In this study we investigated CHRD in cancer and normal adult tissues using the wealth of genome-wide data available in public databases. We found that Chordin is amplified in the DNA of specific cancers such as lung squamous cell and others, although copy number variation did not strictly correlate with higher mRNA expression. In some cancers, such as renal and stomach carcinomas, increased CHRD expression significantly correlated with poor survival. In normal adult human tissues, CHRD mRNA was highest in hepatocytes. Crossveinless-2/BMPER, a component of the Chordin morphogenetic pathway expressed at the opposite side in embryos, was expressed in liver stellate cells. This raises the intriguing possibility that a BMP gradient might be established in the extracellular matrix of the space of Disse that surrounds portal sinusoid capillaries.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Statistical Analyses

Statistical analyses were performed in Excel (Microsoft Corp) and R-Studio via two-tailed Student’s t-test. Differences of means were considered significant at a significance level of 0.05 (p ≤ .05).

Data availability statement

The data that support the findings of this study are from the following resources available in the public domain: cBio Cancer Genomics Portal (https://www.cbioportal.org/), Dependency Map (https://depmap.org/portal/), Genotype-Tissue Expression portal (https://gtexportal.org/home/), Human Protein Atlas (https://www.proteinatlas.org/), and the Cancer Genome Atlas (https://portal.gdc.cancer.gov/).

Abbreviations

BMP=

Bone Morphogenetic Protein

BMPER=

BMP Binding Endothelial Regulator

cBioPortal=

cBio Cancer Genomics Portal

CHRD=

Chordin

CNV=

Copy Number Variantion

CV2=

Crossveinless-2

DepMap=

Dependency Map

FPKM=

Fragments per kilobase of exon per million mapped fragments

GTEx=

Genotype-Tissue Expression

HPA=

Human Protein Atlas

Ntpm=

Normalized transcript per million

scRNA-seq=

Single-cell RNA-sequencing

TCGA=

The Cancer Genome Atlas

Tsg=

Twisted gastrulation

UMAP=

Uniform Manifold Approximation and Projection

vWF-C=

von Willebrand factor C domain.

Additional information

Funding

EAS was supported by the Ruth L. Kirschstein Predoctoral Individual National Research Service F31-Award: 1F31MH131380-01 and EMDR by NIH P20CA016042 to the University of California, Los Angeles Jonsson Comprehensive Cancer Center, and the Norman Sprague Endowment for Molecular Oncology. We thank Lauren V. Albrecht, Alyssa Hill, and Hiroki Kuroda from our laboratory for help in the initial stages of this project.