A Pilot Study Investigating the Expression Levels of Pluripotency-Associated Genes in Rectal Swab Samples for Colorectal Polyp and Cancer Diagnosis and Prognosis

Abstract

Change in gene expression is inevitable in cancer development. With more studies demonstrating the contributions of cancer stem cells (CSCs) in colorectal cancer (CRC) development, this study is aimed at investigating whether rectal swab specimen serves as a tool for detection of dysregulation of CSC or stem cell (SC) markers and at evaluating its potential as a new promising screening method for high-risk patients. Expression levels of 15 pluripotency-associated genes were assessed by quantitative PCR in 53 rectal swab specimens referred for endoscopic screening. Dysregulated genes and joint panels based on such genes were examined for their diagnostic potentials for both polyp and CRC. Out of 15 genes, Oct4, CD26, c-MYC, and CXCR4 showed significantly differential expression among normal, polyp, and CRC patients. A panel of Oct4 and CD26 showed an AUC value of 0.80 ( p = 0.003 ) in identifying CRC patients from polyp/normal subjects, with sensitivity and specificity of 84.6% and 69.2%. A panel of c-MYC and CXCR4 achieved CRC/polyp identification with an AUC value of 0.79 ( p = 0.002 ), with a sensitivity of 82.8% and specificity of 80.0%. The sensitivity for polyp and CRC was 80.0% and 85.7%, respectively. Further analysis showed that higher c-MYC and CXCR4 level was detected in normal subjects who developed polyps after 5-6 years, in comparison with subjects with no lesion developed, and the AUC of the c-MYC and CXCR4 panel increased to 0.88 ( p < 0.001 ), with sensitivity and specificity of 84.4% and 92.3%, respectively, when these patients were included in the polyp group. This study suggests that the Oct4 and CD26 panel is a promising biomarker for distinguishing CRC from normal and polyp patients, whereas the c-MYC and CXCR4 panel may identify polyp and CRC from normal individuals.

Evaluation of Blood Soluble CD26 as a Complementary Biomarker for Colorectal Cancer Screening Programs

“…In this work, the authors did not answer why a marker of CSCs was found downregulated. The gene CD26 should be overexpressed if we look for the metastatic potential of CSCs in tumors [ 19 , 39 ], as was confirmed for the serum protein levels, DPP4 enzymatic activity, and gene transcription in the tumor [ 20 , 21 ]. However, in the early progression steps of this and other cancers, sCD26/DPP4 levels are lower than in healthy donors [ 17 , 18 , 22 , 23 , 24 , 27 , 28 , 29 ].…”

CD26 Induces Colorectal Cancer Angiogenesis and Metastasis through CAV1/MMP1 Signaling

“…A total of 7902 differentially expressed genes were identified, including 3255 upregulated genes and 4647 downregulated genes. As shown in Table S1, certain genes related to pluripotency including SOX2, SOX4, CD133, CXCR4 and CD44 [10]; and genes associated with epithelial to mesenchymal transition (EMT) such as ZEB2 and SNAI1 were upregulated. These preliminary findings reaffirmed the association of CD26+ CRC cells with stem cell properties and activation of EMT process.…”