Genomic and Metabolomic Landscape of Right-Sided and Left-Sided Colorectal Cancer: Potential Preventive Biomarkers.

Ming-Wei Su,Hsiang-Lin Tsai,Bei-Hao Shiu,Ching-Wen Huang,Huang-Chi Chou,Tsung-Kun Chang,Chien-Wei Lin,Wei-Chih Su,Yen-Cheng Chen,Hou-Wei Chu,Tsen-Ni Tsai,Chung-Ke Chang,Jaw-Yuan Wang,Chang-Chieh Wu

doi:10.3390/cells11030527

Abstract

Colorectal cancer (CRC) is the third most common cancer worldwide. The incidence and mortality rates of CRC are significantly higher in Taiwan than in other developed countries. Genes involved in CRC tumorigenesis differ depending on whether the tumor occurs on the left or right side of the colon, and genomic analysis is a keystone in the study and treatment of CRC subtypes. However, few studies have focused on the genetic landscape of Taiwanese patients with CRC. This study comprehensively analyzed the genomes of 141 Taiwanese patients with CRC through whole-exome sequencing. Significant genomic differences related to the site of CRC development were observed. Blood metabolomic profiling and polygenic risk score analysis were performed to identify potential biomarkers for the early identification and prevention of CRC in the Taiwanese population. Our findings provide vital clues for establishing population-specific treatments and health policies for CRC prevention in Taiwan.

Highlights

IntroductionColorectal cancer (CRC) is the third most common cancer worldwide and has a high mortality rate at advanced stages
Mutations in APC were observed in 62% of the samples, which is lower than the APC mutation rate of 75% (Chi-square test, p-value = 0.03) reported for Caucasians in The Cancer Genome Atlas (TCGA) (Figure 2a)
RCRC patients had a later age of onset and a higher rate of poorly differentiated tumors compared to left-sided CRC (LCRC) patients

Summary

Introduction

Colorectal cancer (CRC) is the third most common cancer worldwide and has a high mortality rate at advanced stages. Compared to other developed countries, the incidence and mortality rates of CRC are higher in Taiwan, where CRC has been the most common type of malignancy and the third leading cause of cancer-related deaths since. According to data from the Taiwanese Ministry of Health and Welfare, CRC incidence in Taiwan increased from 32.38 to 66.32 per 100,000 individuals between the years 2000 and 2017. Mortality rates increased from 20.6 per 100,000 individuals in 2009 to 27.3 per 100,000 individuals in 2019 [1]. CRC is not a monolithic disease with a single cause but rather involves several possible genetic mechanisms. Mutations of genes involved in signaling pathways, including APC (the Wnt pathway), KRAS

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