Published online Aug 15, 2019. doi: 10.4251/wjgo.v11.i8.589
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.
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.