Discovery of genes from feces correlated with colorectal cancer progression

Abstract

Abstract. Colorectal cancer (CRC) is considered to develop slowly via a progressive accumulation of genetic mutations. Markers of CRC may serve to provide the basis for decision-making, and may assist in cancer prevention, detection and prognostic prediction. DNA and messenger (m)RNA molecules that are present in human feces faithfully represent CRC manifestations. In the present study, exogenous mouse cells verified the feasibility of total fecal RNA as a marker of CRC. Furthermore, five significant genes encoding solute carrier family 15, member 4 (SLC15A4), cluster of differentiation (CD)44, 3-oxoacid CoA-transferase 1 (OXCT1), placenta-specific 8 (PLAC8) and growth arrest-specific 2 (GAS2), which are differentially expressed in the feces of CRC patients, were verified in different CRC cell lines using quantitative polymerase chain reaction. The present study demonstrated that the mRNA level of SLC15A4 was increased in the majority of CRC cell lines evaluated (SW1116, LS123, Caco-2 and T84). An increased level of CD44 mRNA was only detected in an early-stage CRC cell line, SW1116, whereas OXCT1 was expressed at higher levels in the metastatic CRC cell line CC-M3. In addition, two genes, PLAC8 and GAS2, were highly expressed in the recurrent CRC cell line SW620. Genes identified in the feces of CRC patients differed according to their clinical characteristics, and this differential expression was also detected in the corresponding CRC cell lines. In conclusion, feces represent a good marker of CRC and can be interpreted through the appropriate CRC cell lines. IntroductionColorectal cancer (CRC) is considered to develop slowly via the progressive accumulation of genetic mutations (1,2). Genes that regulate cell growth and differentiation must be altered in cancerous cells in the process of tumorigenesis (3,4). Markers of CRC may provide the basis for decision-making regarding intensive chemotherapy or molecule-targeting drugs in CRC patients (5-7). Therefore, the identification of markers may assist in cancer prevention, detection and prognostic prediction (5,8,9), thereby increasing survival rates (10). Molecular markers (11) have their own clinical significance in CRC (12).In CRC, both sigmoidoscopy and colonoscopy are considered to be the gold standards regarding detection rates. However, these clinical examinations have drawbacks in terms of their risk and inconvenience (13,14

Comprehensive analysis of metastasis-related genes reveals a gene signature predicting the survival of colon cancer patients

“…OXCT1 can be converted into acetyl-CoA during the process of metabolism and takes part in the tricarboxylic acid cycle for the oxidation and the production of adenosine triphosphate (ATP) ( Zhang & Xie, 2017 ). The role of OXCT1 has been implicated in several cancers, included CRC, and OXCT1 was overexpressed in the metastatic CRC cell line CC-M3 ( Lee et al, 2016 ). ACTN4 is a non-muscle-type alpha-actinin, which plays an important role in regulating cytoskeleton organization and is involved in transcriptional regulation of gene expression.…”

Fecal microRNAs as Innovative Biomarkers of Intestinal Diseases and Effective Players in Host-Microbiome Interactions

“…Furthermore, specific fecal miRNAs, such as miRNA-29, were found to be upregulated in rectum cancer and downregulated in colon cancer, suggesting the feasibility of using differential miRNA expression patterns as cancer fingerprints [140]. Importantly, dysregulated miRNAs are abundantly present in stools that contain exfoliated colonocytes and blood as a consequence of the disease [81,134,135,[141][142][143]. Analyses on stool-based miRNAs were shown to be reproducible due to their high stability in feces.…”

Whole Exome Sequencing Identifies Novel Germline Variants of SLC15A4 Gene as Potentially Cancer Predisposing in Familial Colorectal Cancer

“…By being involved in multiple signaling pathways regulating cytokine production and thus innate immune responses, SLC15A4 has been shown to promote colitis in an in vivo mouse model [28,29]. Since high expression of the encoded membrane transporter has been further reported in the feces of CRC patients as well as in early-stage CRC cell lines, an important role of SLC15A4 in initial inflammation-induced colorectal carcinogenesis has been suggested [30]. In this study, we conducted in silico analyses as well as further literature search in order to link the function of the SLC15A4 protein to a genetic basis, potentially contributing to CRC development in the studied family.…”