Table 1.

Molecular profile of CRC progression stages. During CRC progression, oncogenes are activated and tumor suppressor genes are inactivated with each successive stage. Putative tumor suppressors that are linked to metastasis are colored red. Growth factors pathways produce signaling molecules that promote tumor growth; key enzymes and signaling molecules noted in green for activated and blue for inhibited. MSI microsatellite instability, MMR mismatch repair, CIN chromosomal instability. MLH1 MutL homolog 1, PIK3CA phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [40], KRAS K-ras, BRAF B-raf, VIM vimentin [41], FN1 fibronectin 1 [42], CDH2 cadherin 2 [43], APC adenomatous polyposis coli, TP53 tumor protein p53, BAX bcl-2-like protein 4 or apoptosis regulator BAX, SMAD4 small mothers against decapentaplegic homolog 4, TGFBR2 transforming growth factor-beta receptor 2, PTEN phosphatase and tensin homolog [33], E-cadherin epithelial calcium-dependent adhesion [43], CTNNA alpha-catenin encoding gene [44], JUP gamma-catenin encoding gene [45], TGF- β transforming growth factor beta 1, COX2 cyclooxygenase-2, 15-PGDH 15-Hydroxyprostaglandin dehydrogenase, EGFR epidermal growth factor receptor, PI3K phosphoinositide 3-kinase. Adapted from [16,46].

CRC Progression Stage: Normal Cell → Adenomatous Polyps → High-Risk Adenoma → Cancer → Metastasis
Oncogenes		MSI (MMR mutation) (MLH1 methylation) PIK3CA [40]	CIN (e.g., CDC4) KRAS, BRAF	PIK3CA	VIM [41] FN1 [42] CDH2 [43]
Tumor suppressors		APCβ -Catenin		TP53, BAX, SMAD4, TGFBR2PTEN [33]	E-cadherin [43] CTNNA (α-catenin) [44] JUP (γ-catenin) [45] TGF-β
Growth factor pathways	COX2	COX2 15-PGDH EGFR	EGFR	EGFR	EGFR
Affected tissues	None	Epithelium Lamina propria	Epithelium Lamina propria	Epithelium Lamina propria Muscularis mucosa Submucosa	Epithelium Lamina propria Muscularis mucosa Submucosa