OncologyCOMP Gene Coexpresses With EMT Genes and Is Associated With Poor Survival in Colon Cancer Patients
Introduction
Every year, there are 1.2 million new cases of colon cancer (CC) and 0.6 million deaths, establishing CC as an important contributor to worldwide cancer morbidity and mortality.1 In the United States, 49,690 new CC cases were expected to be diagnosed in men and 47,530 in women in 2018.2 Although the overall incidence and mortality of CC have declined over the past 30 y in both men and women,3 the number of early-onset colon cancer (EOCC), in individuals younger than 50 y, continues to rise alarmingly.4 In our previous study using the Surveillance, Epidemiology, and End Results Program Cancer Registries database, we demonstrated that the incidence of CC has continuously increased in every age group (5-y intervals) from 20 to 49 y, with the most impressive increase seen within the age group 40-44.5 The majority (70%-80%) of EOCC cases are sporadic and not attributed to any hereditary cause.4, 6, 7, 8 These EOCC tumors tend to have more aggressive features like mucinous, poorly differentiated histopathology, and signet ring morphology and are often diagnosed at a more advanced stage.4, 5, 6, 9 Moreover, trends toward poorer survival are frequently being seen in EOCC patients.10 Currently, the exact mechanism for these differences between early- and late-onset patients is unknown and could be multifactorial.
Our recently published genomic studies showed that sporadic EOCC expressed unique genes when compared to late-onset colon cancer (LOCC). One of the genes uniquely overexpressed in EOCC patients was the cartilage oligomeric matrix protein (COMP).11 COMP is normally expressed in cartilage and plays a role in chondrogenesis.12 Interestingly, analysis of COMP expression in prostate and breast cancer showed coincident expression of several transcription factors known to mediate epithelial-mesenchymal transition (EMT),13, 14 which is a cellular process that is characterized by cell separation and invasion. During EMT, epithelial cells lose polarity and cell-to-cell adhesion, and gain migratory and invasive properties to become mesenchymal cells.15 It is typically involved in embryonic development, heart valve formation, and other developmental processes. However, EMT has also been implicated in cancer, specifically with increased tumor cell invasion and metastasis.16 As EMT is associated with both metastasis and cell invasion, this supports an imperative need to study the role of COMP in EMT and CC. In this study, we demonstrated a correlation between COMP gene expression and the expression of some key EMT genes and showed that the overexpression of COMP is associated with poor survival in CC patients.
Section snippets
Ethics statement
This study does not involve any human subjects. It utilizes the publicly available deidentified The Cancer Genome Atlas (TCGA) data set. TCGA makes available data sets concerning various cancers including colon adenocarcinoma data set (The Cancer Genome Atlas-Colon Adenocarcinoma) used in this study. This data set contains data on the expression levels of 17,814 genes in tumorous tissue and in normal tissue.
Data set
The Cancer Genome Atlas-Colon Adenocarcinoma cohort was used in our studies.17, 18
COMP coexpresses with epithelial-mesenchymal transition genes
We investigated the role of COMP in EMT by comparing COMP mRNA expression relative to that of EMT genes using 286 CC patients. Results showed coexpression/positive correlation between COMP levels and the EMT markers of snail family transcriptional repressor 1 (SNAI1), SNAI2, zinc finger E-box binding homeobox 1 (ZEB1), ZEB2, twist family BHLH transcription factor 1 (TWIST1), TWIST2, periostin (POSTN), fibronectin (FN1), vimentin (VIM), collagen (COL1A1), N-cadherin (CDH2), and matrix
Discussion
The implication of COMP protein in disease has been well documented in connective tissue disorders such as pseudoachondroplasia and multiple epiphyseal dysplasia type 1.25, 26, 27 However, elucidating COMP's role in tumor development and cancer progression is only in its infancy. We previously reported on the gene expression landscape of EOCC relative to LOCC and identified COMP as a potential candidate target, which informed us of the nature of the molecular environment of CC with respect to
Acknowledgment
The authors thank the patients without whom this work would not be possible.
Authors' contributions: V.N.N. performed conception and design; L.E.N. performed writing the article, data analysis, and interpretation of data; D.C., P.N.O., and A.C. performed data acquisition; R.R. performed article revision and concept; J.J. performed design, conception, article revision, data interpretation, and data analysis. Funding: This work was supported by the SAGES research grant awarded to V.N.N.
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Early-Onset Colorectal Cancer
2022, Surgical Oncology Clinics of North AmericaCitation Excerpt :Expression also increases sequentially as the CRC stage progresses from I to IV.40 Higher COMP expression is associated with poorer survival outcomes in EOCRC patients.41 COMP has shown promise as a prognostic or disease monitoring marker, given its ability to be measured in the serum.42
Cartilage Oligomeric Matrix Protein, COMP may be a Better Prognostic Marker Than CEACAM5 and Correlates With Colon Cancer Molecular Subtypes, Tumor Aggressiveness and Overall Survival
2022, Journal of Surgical ResearchCitation Excerpt :Additionally, CMS4 is characterized by activation of the TGFß signaling pathway, which has been well established as a contributor to cancer metastasis through induction of EMT gene expression.35-37 COMP is co-expressed with key EMT factors.16 The high levels of COMP observed specifically in CMS4 further suggest a role in carcinogenic EMT induction.
Increasing Incidence of Colon Cancer in the Young: Assessing the Tumor Biology
2019, Journal of the American College of SurgeonsCitation Excerpt :Moreover, our recently published analysis of RNAseq gene expression data (n = 286, CC primary tumors) from the COAD-TCGA dataset has shown coexpression of COMP with epithelial to mesenchymal transition-linked genes,18 a mechanism that is implicated in cancer metastasis and invasion.30,31 Further Kaplan Meier survival analysis of the same samples revealed significantly poorer overall survival of patients expressing higher COMP mRNA levels.18 Colon cancer in young patients is often diagnosed at advanced stages and presents with more aggressive tumors.9
Cartilage oligomeric matrix protein acts as a molecular biomarker in multiple cancer types
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