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
Research background

Colon cancer affects 1.2 million people around the world and causes about 0.6 million deaths annually. Although the overall incidence and mortality is decreasing, there has been an alarming increase in early-onset cases (< 50 years). These younger patients are often diagnosed at late stages with more aggressive tumors and tend to have poorer survival.

Research motivation

We previously showed that secreted frizzled-related protein 4 (SFRP4), speculated to play an essential role in cancer by inhibiting epithelial mesenchymal transition (EMT), is over-expressed in younger patients.

Research objectives

The aim of our study was to investigate whether there is a correlation between SFRP4 expression and EMT-linked genes in colon cancer and whether SFRP4 over-expression affects patient survival using a larger cohort of patients.

Research methods

Correlation between SFRP4 expression and EMT-linked genes along with survival analysis were performed using the University of California Santa Cruz Cancer browser interface using publicly available The Cancer Genome Atlas-colon adenocarcinoma cohort of colon cancer cases.

Research results

SFRP4 is co-expressed with EMT-linked markers, such as CDH2, FN1, VIM, TWIST1, TWIST2, SNAI1, SNAI2, ZEB1, ZEB2, POSTN, MMP2, MMP7, MMP9, and COL1A1, in colon cancer patients. SFRP4 expression negatively correlated with the EMT-linked suppressors CLDN4, CLDN7, TJP3, MUC1, and CDH1. Mesenchymal-like samples showed higher expression of SFRP4 and EMT-linked markers relative to epithelial-like samples. This implicates SFRP4 in colon cancer EMT mechanism. Additionally, patients with colon tumors over-expressing SFRP4 presented with significantly poorer overall survival.

Research conclusions

Results of this study suggest a potential role of SFRP4 in colon cancer aggressiveness, disease progression, and poorer patient survival. Although the role of SFRPs including SFRP4 as WNT signaling inhibitors is well documented in the literature, data presented in this manuscript suggest that the SFRP family proteins might also activate WNT signaling and promote cell proliferation, therefore demonstrating its oncogenic potential and suggesting its mechanism of action might be context dependent.

Research perspectives

More extensive and detailed mechanistic in vitro and in vivo studies will have to be performed to confirm these initial observations in colon cancer patients.