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

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.

Salivary metabolomics with machine learning for colorectal cancer detection

“…Right‐sided CRC has a higher mortality rate and worse prognosis than left‐sided CRC, and both genetic and metabolomic differences between these two sides have been reported. 58 , 59 , 60 Therefore, we evaluated the difference between the left and right colon on prediction accuracy. There was no significant difference between tumor locations even in the training and validation data (Figure S7 ).…”

Comprehensive Review of Biomarkers for the Treatment of Locally Advanced Colon Cancer

“…A Dutch study including 10,878 patients with LACC indicated that old age (≥70 year), incomplete resection margin, and nodal positivity status were significantly associated with poor survival [ 4 ]. The site of colon cancer development is another key prognostic factor for LACC ( Figure 2 ) [ 55 , 56 , 57 , 58 ]. Differences in the embryonic origin divide the colon into left and right sides.…”

Integrated single-cell RNA-seq analysis identifies immune heterogeneity associated with KRAS/TP53 mutation status and tumor-sideness in colorectal cancers

“…Colorectal cancer and its TME are remarkably heterogeneous, both anatomically and genetically ( 9 – 11 ). The tumor anatomical location, which is commonly described as left- or right-sided colorectal cancers, contributes to the heterogeneity ( 12 , 13 ). In addition, studies have revealed the genetic heterogenicity of colorectal cancers, as evidenced by concurrent high- and low-frequency mutations and transcription profile drift ( 10 , 14 – 16 ).…”

“…With respect to anatomical heterogeneity, the right-sided intestine originates from embryonic midgut, while the left-sided large intestine originates from embryonic hindgut. This ontogenetic divergency may explain the disparity in gene expression profiles between the left- and right-sided colon, as well as colorectal cancers ( 13 ). Clinical data indicated that left-sided colorectal cancer has a better prognosis than right-sided cancers, and showed increased susceptibility to first-line FOLFIRI plus cetuximab therapy ( 12 ).…”

“…Clinical data indicated that left-sided colorectal cancer has a better prognosis than right-sided cancers, and showed increased susceptibility to first-line FOLFIRI plus cetuximab therapy ( 12 ). Although the underlying mechanisms remain unclear, studies have suggested that the disparity in immune infiltration between left- and right-sided colorectal tumors may partially explain the clinical difference ( 13 , 21 – 23 ). Moreover, in-depth analyses are still required to fully elucidate this conceivable biological and immunological distinction.…”