br Methods mRNA expression of COMP was compared
Methods: mRNA K 252a of COMP was compared to that of EMT markers using the UCSC Cancer Genomics Browser. Survival analysis was performed using the UCSC Xena Browser for cancer genomics.
Results: Expression analysis revealed coexpression of COMP with the EMT markers CDH2, FN1, VIM, TWIST1, TWIST2, SNAI1, SNAI2, ZEB1, ZEB2, POSTN, MMP2, MMP9, and COL1A1. Samples that were more mesenchymal had higher expression levels of COMP and EMT markers, thus suggesting a potential role of COMP in EMT. Patients with increased COMP expression presented with poorer overall survival compared to patients with no change or reduced COMP expression (P ¼ 0.02).
Conclusions: These findings reveal COMP as a potential biomarker for CC especially in more aggressive CC and CC in young patients, with a likely role in EMT during tumor metastasis and invasion, and a contributing factor to patient survival.
Published by Elsevier Inc.
E-mail address: [email protected] (V.N. Nfonsam).
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, con-tinues 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.4,6-8 These EOCC tumors tend to have more aggressive features like mucinous, poorly differentiated histopathology, and sig-net ring morphology and are often diagnosed at a more advanced stage.4-6,9 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 overex-pressed 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 em-bryonic development, heart valve formation, and other devel-opmental 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.
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.