Molecular pathological classification of colorectal cancer—an update

Abstract

Colorectal cancer (CRC) has a broad range of molecular alterations with two major mechanisms of genomic instability (chromosomal instability and microsatellite instability) and has been subclassified into 4 consensus molecular subtypes (CMS) based on bulk RNA sequence data. Here, we update the molecular pathological classification of CRC with an overview of more recent bulk and single-cell RNA data analysis for development of transcriptional classifiers and risk stratification methods, taking into account the marked inter-tumoural and intra-tumoural heterogeneity of CRC. The importance of the stromal and immune components or tumour microenvironment (TME) to prognosis has emerged from these analyses. Attempts to remove the contribution of the tumour microenvironment and reveal neoplastic-specific transcriptional traits involved identification of the CRC intrinsic subtypes (CRIS). The use of immunohistochemistry and digital pathology to implement classification systems are evolving fields. Conventional adenoma versus serrated polyp pathway transcriptomic analysis and characterisation of canonical LGR5+ crypt base columnar stem cell versus ANXA1+ regenerative stem cell phenotypes emerged as key properties for improved understanding of transcriptional signals involved in molecular subclassification of colorectal cancers. Recently, classification by three pathway-derived subtypes (PDS1-3) has been developed, revealing a continuum of intrinsic biology associated with biological, stem cell, histopathological, and clinical attributes.

Therapeutic effects of Buzhong Yiqi decoction in patients with spleen and stomach qi deficiency after routine surgery and chemotherapy for colorectal cancer

“…Colorectal cancer predominantly affects the left half of the colon, including the descending colon, sigmoid colon, and rectum[ 6 ]. The disease often manifests with subtle symptoms in the early stages, leading to delayed diagnosis until the intermediate or advanced stages are reached.…”

Development of a new flippase-dependent mouse model for red fluorescence-based isolation of KrasG12Doncogene-expressing tumor cells

“…Most of these tumors are triggered by the loss of tumor suppressor Apc, which leads to hyperproliferation of epithelial cells (Cancer Genome Atlas 2012). Oncogenic mutations in the KRAS gene are frequent mutational changes associated with the progression of adenomas after the loss of Apc (Dunne and Arends 2024). To investigate the functionality of the Kras RR allele in the context of intestinal tumors, we used a model with a conditional allele (cKO) of the Apc gene whose exon is flanked by two loxP sites.…”

Smad4and TGF-β1 dependent gene expression biomarkers in conditional intestinal adenoma, organoids and colorectal cancer

“…Moreover, RNA based molecular prognostic classifiers of colorectal cancer have developed in line with the clinically applied breast cancer equivalents, and have identified several clusters (e.g. CRISB) that include a stromal based signature that correlate with poor prognosis in colorectal cancer [7][8][9] . Gene-pathway specific gene expression biomarkers based on driver gene variants and their dependencies are overall less well validated.…”