Prognostic Factors Involved in the Epithelial–Mesenchymal Transition Process in Colorectal Cancer Have a Preponderant Role in Oxidative Stress: A Systematic Review and Meta-Analysis

Abstract

Epithelial-to-mesenchymal transition (EMT) is one of the most accepted mechanisms leading to metastasis, which is responsible for most of the cancer-related deaths. In order to identify EMT-related biomarkers able to predict clinical outcomes in colorectal cancer (CRC), a systematic review and meta-analysis of prognostic factors associated to overall survival (OS) and progression free survival (PFS) was conducted. The systematic literature search included studies from June 2014 to June 2019 available at PubMed and Scopus databases. Meta-analysis was performed for those markers appearing in minimum three works with a total number of 8656 participants. The rest were enlisted and subjected to functional enrichment. We identified nine clinical biomarkers and 73 EMT-related molecular biomarkers associated to OS and/or PFS in CRC. The significant enrichment of biomarkers found involved in cellular oxidoreductase activity suggests that ROS generation plays an active role in the EMT process. Clinical practice needs new biomarkers with a reliable prognostic value able to predict clinical outcomes in CRC. Our integrative work supports the role of oxidative stress in tumorigenesis and EMT progress highlighting the importance of deciphering this specific mechanism to get a better understanding of metastasis.

Long non-coding RNA EVADR induced by Fusobacterium nucleatum infection promotes colorectal cancer metastasis

“…EMT is an important process for cancer progression that renders epithelial cancer cells more invasive (Parisi et al, 2020;Tsai et al, 2012). Since cancer cell invasiveness and mobility can be reflected by actin filaments (F-actins), the ability of F. nucleatum to influence the actin cytoskeleton in CRC motility was evaluated by F-actin staining.…”

"GDF-15 Signaling Leading to Epithelial-to-Mesenchymal Transition in Colorectal Cancer - a Literature Review"

“…Allele loss of chromosome 18, microsatellite instability-deficient mismatch repair (MSI/dMMR) , and mutations in KRAS have been shown to negatively affect prognosis in cancer patients (30,31). According to the research on EMT biomarkers, low expression of E-cadherin (32) and high expression of N-cadherin (21), Slug, and Vimentin (33) have been associated with a worse prognosis in CRC (34).…”

Microenvironmental Reactive Oxygen Species in Colorectal Cancer: Involved Processes and Therapeutic Opportunities

“…The PI3K/Akt pathway is also involved in the inhibition of glycogen synthase kinase-3 (GSK-3β), which confers stabilization to β-catenin to activate the transcript of Slug and vimentin [72]. All these inputs received by the cell lead to the activation of the EMT transcription factors (TFs) SNAI1/2, SLUG, TWIST, and ZEB1/2 [73] in colon tissues [74,75].…”