TABLE 5.

Potential diagnostic and therapeutic targets from collagen remolding

Process	Description	Implications for HCC diagnosis or treatment
Collagen secretion	Dysregulation leads to accumulation of aberrant collagen structures, contributing to a tumor-permissive microenvironment.	Targeting collagen secretion mechanisms (eg, inhibiting synthesis or transport) may reduce tumor-promoting effects of ECM.70,82,88,89
Collagen modification	Altered glycosylation impacts structure and function of ECM in HCC.	Targeting enzymes involved in collagen modification (eg, glycosyltransferases, glycosidases) could restore normal collagen glycosylation and attenuate tumor-promoting effects.66,90
Collagen interaction	Understanding molecular interactions between collagen and cell surface receptors (eg, integrins, DDRs) can identify therapeutic targets.	Targeting these receptors or modulating their signaling pathways may disrupt tumor-promoting cell-ECM cross talk.46,91
Collagen degradation	Dysregulation contributes to ECM remodeling and tumor progression.	Targeting enzymes responsible for collagen degradation (eg, MMPs) may prevent excessive ECM remodeling and inhibit tumor cell invasion and metastasis.36

Abbreviations: DDR, discoidin domain receptor; ECM, extracellular matrix; MMPs, matrix metalloproteinase.