Correlation between prognostic markers and clinical parameters in hepatocellular carcinoma: Pathophysiological aspects to therapeutic targets

Table 2 Overview of prognostic markers as therapeutics strategies in hepatocellular carcinoma

Prognostic markers	Therapeutics in HCC	Ref.
MEX3A	In HCC, MEX3A could be a new regulator of the Hippo signaling pathway and a possible target for treatment	[16,54]
	A novel treatment approach for progressive and sorafenib-resistant HCC is provided by the combined data, which further clarifies the possible role and mechanism of MEX3A in HCC
	Via an antiangiogenic mechanism rather than by specifically targeting HCC cells, dovitinib selectively suppresses HCC development and metastasis
	MEX3A inhibition could enhance the efficacy of standard HCC treatments such as sorafenib, lenvatinib, or immunotherapy
	Combining MEX3A-targeting strategies with PD-L1 inhibitors could improve immune response against HCC
APOB	Not determined
AFP	According to recent research, AFP inhibition significantly suppresses the malignant tendencies of HCC cells, causing cancer cell death and preventing their invasion, metastasis, and proliferation	[55,69]
	For this reason, AFP is essential for the malignant development of HCC
	In the development, diagnosis, and management of HCC, AFP is a two-edged sword
	Assessing AFP levels in clinical practice is crucial for the early identification, diagnosis, and management of HCC
	Medical practitioners can guide clinical decision-making by tracking changes in AFP levels, which allows them to track the course of the disease and the effectiveness of treatment
	Additionally, physicians can employ AFP vaccinations to produce CD8+ T lymphocytes that are specific to AFP and destroy cancer cells
	Furthermore, AFP and immunotherapy together can increase the effectiveness of treatment
	Evidence for the negative predictive impact of increased baseline AFP raises the possibility that AFP plays a part in primary resistance to sorafenib treatment
CTCs	Moreover, CTCs are excellent choices for creating preclinical models (particularly 3D organoid cultures) for drug screening, disease modeling, genome editing, tumor immunity research, and the creation of organ-like biobanks	[61,62]
	According to recent research, CTCs are promising candidates for early diagnosis, assessing the prognosis of metastases or recurrences, and possibly serving as a possible target for therapy in patients with HCC
	In the future, it will be used as a novel indication in therapeutic settings
SAMD13	The potential function of SAMD13 as a therapeutic target and a promising biomarker for prognosis in HCC is highlighted by the features of its involvement in patients with HCC utilizing a variety of bioinformatics techniques	[51]
	While SAMD13 shows promise as a prognostic indicator, its potential as a therapeutic target in HCC requires further investigation
	Understanding the precise biological functions of SAMD13 in HCC progression and its interactions within the tumor microenvironment is essential
Agrin	Agrin is often overexpressed, has a significant role in the carcinogenic characteristics of HCC, and is a desirable target for antibody treatment	[64]
	Incorporating Agrin inhibitors with existing treatments, such as tyrosine kinase inhibitors or immunotherapies, may enhance overall therapeutic efficacy
	This combination strategy could potentially overcome resistance mechanisms and improve patient outcomes
GPC3	GPC3 knockdown by siRNA increased the suppression effects of curcumin on Wnt/β-catenin signaling	[43,66,73]
	Small molecules that interfere with GPC3-mediated signaling pathways are an appealing therapeutic strategy that may be used in HCC patients; however, as of yet no small molecules that target GPC3 have been developed or tested in HCC patients. Small-molecule GPC3 drugs may provide greater efficacy, stability, and safety for the treatment of HCC
	Further research is required to develop GPC3 targeting small molecular compounds
	Numerous clinical trials involving GPC3 are currently underway, and several novel GPC3-targeted therapeutic approaches, such as the GPC3 vaccine, anti-GPC3 immunotoxin, combined therapy with immune checkpoint blockades, and chimeric antigen receptor T or NK cells, have recently surfaced with promising outcomes
	Current research on GPC3 expression in human HCC, GPC3 regulation molecular mechanisms, and GPC3-targeting antibodies
	Furthermore, several immunotherapies that target GPC3 have been created, such as chimeric-antigen-receptor-modified cells, anti-GPC3 immunotoxins, and GPC3 vaccines
	After summarizing and evaluating the physicochemical characteristics and structure of GPC3 molecules, the authors go over their biological roles and clinical diagnostic uses before investigating GPC3-based diagnosis and therapy approaches

HCC: Hepatocellular carcinoma; APOB: Apolipoprotein B; CTC: Circulating tumor cell; AFP: Alpha-fetoprotein; GPC3: Glypican-3; 3D: Three-dimensional; NK: Natural killer.