Collagen in hepatocellular carcinoma: A novel biomarker and therapeutic target

Abstract

HCC is globally recognized as a major health threat. Despite significant progress in the development of treatment strategies for liver cancer, recurrence, metastasis, and drug resistance remain key factors leading to a poor prognosis for the majority of liver cancer patients. Thus, there is an urgent need to develop effective biomarkers and therapeutic targets for HCC. Collagen, the most abundant and diverse protein in the tumor microenvironment, is highly expressed in various solid tumors and plays a crucial role in the initiation and progression of tumors. Recent studies have shown that abnormal expression of collagen in the tumor microenvironment is closely related to the occurrence, development, invasion, metastasis, drug resistance, and treatment of liver cancer, making it a potential therapeutic target and a possible diagnostic and prognostic biomarker for HCC. This article provides a comprehensive review of the structure, classification, and origin of collagen, as well as its role in the progression and treatment of HCC and its potential clinical value, offering new insights into the diagnosis, treatment, and prognosis assessment of liver cancer.

FIGURE 1

The diagnostic, therapeutic, and prognostic value of collagen in HCC.

FIGURE 2

The role of collagen in remodeling of the immune microenvironment. (A) The tumor microenvironment contains few fibroblasts and a small amount of secreted collagen, with normal infiltration of immune cells; in contrast, (B) shows a tumor microenvironment with a significant number of activated fibroblasts that secrete large amounts of collagen in a disorganized manner, resulting in a deficiency of immune cells within the tumor and thereby facilitating tumor vascular invasion and metastasis; (C) demonstrates that collagen induces immunosuppression in immune cells through receptor interactions and enhances the survival capabilities of tumor cells; (D) shows that the dense arrangement of collagen fibers surrounding the tumor obstructs the infiltration of immune cells such as CD8+ T cells and NK cells, leading to immune evasion. Abbreviations: LAIR-1, leukocyte-associated immunoglobulin-like receptor-1; NK cell, natural killer cell; TAM, tumor-associated macrophages.