High Expression of Stem Cell-Related Genes in Polyps with Villous Features and High-Grade Dysplasia Support Malignant Phenotype and Colorectal Carcinogenesis.

Ibrahim Sahin,Abdulgani Tatar,Haktan Erdem,Ahmet Ceylan,Betül Gündoğdu

doi:10.31557/apjcp.2021.22.8.2429

Abstract

Objective:The aim of this project is to identify the differences in expression levels of stem cell related genes (SCRGs) in normal colon tissue, histopathologically staged colon polyps and colon cancer, and to explain the role of SCRGs in the formation of CC and for contributing the practical usage of SCRGs in the diagnosis and treatment of CC. Methods:Normal colon tissue, hyperplastic polyps, histopathologically (HGD and LGD) staged tubular, tubulovillous and villous polyps and colon cancer paraffin tissue (FFPE) samples were used. Transcription factor genes (OCT4, KLF4, SOX2, MYC, NANOG, and REX1) and cell surface markers (CD133, LGR5), which are associated with embryonic stem cells, induced pluripotent stem cells, and cancer stem cells, have been selected for measuring expression levels from the selected tissues. After isolation of total RNA from FFPE tissues, SCRGs expressions were measured by RT-qPCR method. Results:SCRGs expression differences were detected in normal–adenoma–cancer progression. A significant increase was observed in the expression of LGR5 (p: 0.01) and PROM1 (p: 0.005) genes in villous HGD polyps, LGR5 (p: 0.003) gene in G1, and LGR5 (p: 0.0002) and MYC (p: 0.002) genes in G2 stage tumor tissues. When compared with each other, a significant increase in SCRGs expression is noticeable in the formation from adenoma to cancer tissues regarding malign phenotype. Conclusion:This study shows that the increase of SCRGs expressions occurs with high-grade dysplasia (HGD), villous features, and the malignant phenotype. Increased expression levels of LGR5, PROM1, KLF4, SOX2, and MYC in HGD and cancerous tissues support the malignant phenotype and the existence of cancer stem cells and demonstrate that they can be used to assess diagnosis and prognosis. Identification of tissue-specific SCRGs expressions will help design new therapies to control the development and progression of colonic neoplasia.

Highlights

Colorectal cancer (CC) is one of the most common cancers worldwide, and between one and two million new cases are diagnosed each year, making CC the fourth most common cancer
This study shows that the increase of stem cell related genes (SCRGs) expressions occurs with highgrade dysplasia (HGD), villous features, and the malignant phenotype
SCRGs expressions were present in normal tissues, possibly due to intestinal stem cells; even their expression levels were higher than most polyps

Summary

Introduction

Colorectal cancer (CC) is one of the most common cancers worldwide, and between one and two million new cases are diagnosed each year, making CC the fourth most common cancer. It is the third most common cause of cancer death, with 700,000 deaths annually. From benign adenoma to malignant adenocarcinoma and metastasis, CC formation follows a long, gradual process (Harris and McCormick, 2010). All types of adenomas show dysplasia with abnormal glandular architecture and damaged intracellular structures. The degree of dysplasia is varied, and in severe dysplasia, malignancy risk increases

Methods

Results

Conclusion