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

Ryan Wai-Yan Sin,Lui Ng,Xue Li,Dominic Chi-Chung Foo,May Sau-Yee Fan,Deepak Narayanan Iyer,Oswens Siu-Hung Lo,Wai-Lun Law

doi:10.1155/2021/4139528

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.

Highlights

Colorectal cancer (CRC) has become the third most prevalent cancer worldwide in males and second in females, reaching over 1.8 million incidences and 0.8 million deaths in total in 2018 [1]
In this study, we aim to investigate whether dysregulation of stem cell markers, including Oct4, ALDH1A1, CD133, CD166, CD24, CD26, CD29, CD44, cMYC, CXCR4, EpCAM, LGR5, LRIG1, Msi1, and SOX2, is detected in patients with CRC and to evaluate if rectal swab samples may serve as a tool for gene expression analysis and CRC screening
No stage-dependent variation was detected in the c-MYC and CXCR4 panel value, whereas a trend of increasing panel value in late-stage cases was observed in the Oct4 and CD26 panel, the result was not significant (p = 0:059, Figure 6(a))

Summary

Introduction

Colorectal cancer (CRC) has become the third most prevalent cancer worldwide in males and second in females, reaching over 1.8 million incidences and 0.8 million deaths in total in 2018 [1]. Only 39% of CRC patients were diagnosed at their less-invasive localized stage, when their five-year survival rate reaches 90% [3]. Such rate was reduced to 71% and, drastically, to 14% for regional and distant stage of cancer. These emphasized the essentials of early detection of colorectal dysplasia, including polyps, adenoma, and CRC, for patients to reduce both chances of developing tumor and severity of cancer if present

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