Evolving landscape of biomarkers in colorectal cancer: From interleukin-8 to integrated multi-marker strategies

Table 3 Summary of established and emerging biomarkers in colorectal cancer

Biomarker	Prevalence	Clinical utility	Evidence level	Guideline recommendation	Ref.
MMR/MSI	15% stage II/III	Predictive for immunotherapy; prognostic in stage II	Level I	Universal testing recommended	[23-26]
KRAS	Approximately 40%	Prognostic (interacts with laterality); predictive in metastatic setting	Level II	Recommended for all patients	[28,29,32]
BRAF V600E	5%-10%	Prognostic in MSS; predictive in metastatic setting	Level II	Recommended for all patients	[30,31]
HER2	3%-5%	Predictive for anti-HER2 therapy in metastatic disease	Level II	Recommended in metastatic setting	[33-35]
NTRK	< 1%	Predictive for TRK inhibitors	Level II	Recommended (tumor-agnostic)	[36,37]
PIK3CA	10%-15%	Predictive for aspirin benefit (secondary prevention)	Level II	NCCN recommends testing	[38-41]
CEA	N/A	Prognostic; surveillance	Level II	Recommended perioperatively	[22,27]
ctDNA	N/A	MRD detection; treatment monitoring	Level II (prognostic)	Not routine outside trials; NCCN recommends in clinical trials	[42-46]
			Level I (emerging interventional)
IL-8	Variable	Investigational; prognostic potential	Level III	Not recommended	[10,19-21,31,35-37,59]
Methylation (SEPT9, etc.)	Variable	Screening; diagnostic	Level II	FDA-approved for screening	[48]
SETD7	Variable	Investigational; diagnostic potential	Level III	Not recommended	[49]
Metabolomic signatures	Variable	Investigational; diagnostic potential	Level III	Not recommended	[50]

MMR: Mismatch repair; MSI: Microsatellite instability; MSS: Microsatellite stable; KRAS: Kirsten rat sarcoma viral oncogene homolog; BRAF: V-Raf murine sarcoma viral oncogene homolog B; HER2: Human epidermal growth factor receptor 2; TRK: Tyrosine receptor kinase; NTRK: Neurotrophic tyrosine receptor kinase; PIK3CA: Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; CEA: Carcinoembryonic antigen; ctDNA: Circulating tumor DNA; MRD: Minimal residual disease; IL-8: Interleukin-8; SEPT9: Septin 9; SETD7: SET domain containing 7, histone lysine methyltransferase; FDA: Food and Drug Administration; NCCN: National Comprehensive Cancer Network; N/A: Not applicable.