Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Aug 15, 2019; 11(8): 589-598
Published online Aug 15, 2019. doi: 10.4251/wjgo.v11.i8.589
SFRP4 expression correlates with epithelial mesenchymal transition-linked genes and poor overall survival in colon cancer patients
Landry E Nfonsam, Jana Jandova, Hunter C Jecius, Pamela N Omesiete, Valentine N Nfonsam
Landry E Nfonsam, Department of Genetics, Children’s Hospital of Eastern Ontario, Ottawa, Ontario K1H 8L1, Canada
Jana Jandova, Hunter C Jecius, Pamela N Omesiete, Valentine N Nfonsam, Department of Surgery, University of Arizona, Tucson, AZ 85724, United States
Author contributions: Nfonsam LE and Jandova J contributed equally to this work; Nfonsam LE, Jandova J, and Nfonsam VN designed the research; Nfonsam LE, Jandova J, Jecius HC, and Omesiete PN performed the research; Nfonsam LE and Jandova J analyzed and interpreted data; Nfonsam LE, Jandova J, Jecius HC, Omesiete PN, and Nfonsam VN wrote the paper.
Supported by the SAGES research grant (to Nfonsam VN).
Institutional review board statement: This study does not involve human subjects. It utilizes the publicly available de-identified colon adenocarcinoma data set from The Cancer Genome Atlas.
Conflict-of-interest statement: All authors declare no conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Valentine N Nfonsam, MD, Associate Professor, Department of Surgery, University of Arizona, 1501 N Campbell Avenue, Tucson, AZ 85724, United States.
Received: February 14, 2019
Peer-review started: February 15, 2019
First decision: March 14, 2019
Revised: April 2, 2019
Accepted: May 23, 2019
Article in press: May 23, 2019
Published online: August 15, 2019

Colon cancer is among the most commonly diagnosed cancers in the United States with an estimated 97220 new cases expected by the end of 2018. It affects 1.2 million people around the world and is responsible for about 0.6 million deaths every year. Despite decline in overall incidence and mortality over the past 30 years, there continues to be an alarming rise in early-onset colon cancer cases (< 50 years). Patients are often diagnosed at late stages of the disease and tend to have poor survival. We previously showed that the WNT “gatekeeper” gene, secreted frizzled-related protein 4 (SFRP4), is over-expressed in early-onset colon cancer. SFRP4 is speculated to play an essential role in cancer by inhibiting the epithelial mesenchymal transition (EMT).


To investigate the correlation between SFRP4 expression and EMT-linked genes in colon cancer and how it affects patient survival.


SFRP4 expression relative to that of EMT-linked genes and survival analysis were performed using the University of California Santa Cruz Cancer Browser interface.


SFRP4 was found to be co-expressed with the EMT-linked markers CDH2, FN1, VIM, TWIST1, TWIST2, SNAI1, SNAI2, ZEB1, ZEB2, POSTN, MMP2, MMP7, MMP9, and COL1A1. SFRP4 expression negatively correlated with the EMT-linked suppressors CLDN4, CLDN7, TJP3, MUC1, and CDH1. The expression of SFRP4 and the EMT-linked markers was higher in mesenchymal-like samples compared to epithelial-like samples which potentially implicates SFRP4-EMT mechanism in colon cancer. Additionally, patients overexpressing SFRP4 presented with poor overall survival (P = 0.0293).


Considering the implication of SFRP4 in early-onset colon cancer, particularly in the context of EMT, tumor metastasis, and invasion, and the effect of increased expression on colon cancer patient survival, SFRP4 might be a potential biomarker for early-onset colon cancer that could be targeted for diagnosis and/or disease therapy.

Keywords: Secreted frizzled-related protein 4, Epithelial mesenchymal transition, Colon cancer, Survival

Core tip: We have previously shown that secreted frizzled-related protein 4 (SFRP4) is over-expressed in colon cancer, especially in patients younger than 50 years. As these early-onset colon cancers tend to be more aggressive and negatively affecting patients’ survival, we sought to evaluate whether SFRP4 is co-expressed with epithelial-mesenchymal transition-linked genes that play key roles in cancer progression. Our results using a large colon adenocarcinoma-The Cancer Genome Atlas cohort revealed that SFRP4 is over-expressed in colon cancer patients together with epithelial-mesenchymal transition-linked genes. Moreover, colon cancer patients with high expression levels of SFRP4 showed significantly poorer survival relative to colon cancer patients with lower SFRP4 expression.