Tumor microenvironment-driven microRNA dysregulation: Key interactions in colorectal cancer progression

Table 2 MicroRNA’s associated with colorectal cancer molecular subtype and their clinical relevance[150,151]

CMS class	Molecular features	Frequency (%)	Immune phenotype	Prognosis	miR	Ref.
CMS1: Immune MSI	CIMP (increase); BRAFV600E m; hypermutated; KRASwt; TP53wt	14	Immune activation and infiltration LTC and NK	Intermediate prognosis; good early disease control but poor survival after relapse	miR-625 (increase), miR-31 (increase), miR-155 (increase)	Adam et al[150]
CMS2: Canonical (epithelial differentiation)	CIMP negative; BRAFwt; KRASwt; TP53m	37	WNT and MYC activation. Immune dessert	Best overall	miR-592 (increase), miR-552 (increase)	Adam et al[150]
CMS3: Metabolic	CIMP negative; BRAFwt; KRASm; TP53wt	13	Metabolic deregulation	Poor immunogenicity	miR-625 (increase)	Adam et al[150]
CMS4: Mesenchymal	CIMP negative; BRAFwt; KRASwt	23	Stromal infiltration (macrophages) TGF-β activator-CSC EMT and angiogenesis	Worse and poor survival. Resistant standard treatment	miR-625 (decrease), miR-143 (increase) (CMS4 vs CMS2); miR-200 (decrease), miR-218 (increase)	Adam et al[150]; Gherman et al[151]

CMS: Consensus molecular subtype; CIMP: CpG island methylator phenotype; wt: Wild type; m: Mutation; NK: Natural killer; TGF: Transforming growth factor; CSC: Cancer stem cell; EMT: Epithelial-mesenchymal transition; miR: MicroRNA.