Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, with significant racial and ethnic disparities in incidence, tumor biology, and clinical outcomes. Hispanic/Latino (H/L) patients tend to be diagnosed at younger ages and more advanced stages than Non-Hispanic White (NHW) patients, yet the molecular mechanisms underlying these disparities remain poorly understood. Key oncogenic pathways, including RTK/RAS, TGF-beta, WNT, PI3K, and TP53, play pivotal roles in tumor progression, treatment resistance, and response to targeted therapies. However, ethnicity-specific alterations within these pathways remain largely unexplored. This study aims to compare pathway-specific mutations in HCC between H/L and NHW patients, assess tumor mutation burden, and identify ethnicity-associated oncogenic drivers using publicly available datasets. Findings from this analysis may inform precision medicine strategies for improving early detection and targeted therapies in underrepresented populations.

We conducted a bioinformatic analysis using publicly available HCC datasets to assess mutation frequencies in RTK/RAS, TGF-beta, WNT, PI3K, and TP53 pathway genes. This study included 547 patients, consisting of 69 H/L patients and 478 NHW patients. Patients were stratified by ethnicity (H/L vs. NHW) to evaluate differences in mutation prevalence. Chi-squared tests were used to compare mutation frequencies, while Kaplan-Meier survival analysis assessed overall survival differences associated with pathway-specific alterations in both populations.

Significant differences were observed in the RTK/RAS pathway-related genes, particularly in FGFR4 mutations, which were more prevalent in H/L patients compared to NHW patients (4.3% vs. 0.6%, p = 0.02). Additionally, IGF1R mutations exhibited borderline significance (7.2% vs. 2.9%, p = 0.07). In the PI3K pathway, INPP4B alterations were more frequent in H/L patients than in NHW patients (4.3% vs. 1%, p = 0.06), while, in the TGF-beta pathway, TGFBR2 mutations were more common in H/L patients (2.9% vs. 0.4%, p = 0.07), suggesting potential ethnicity-specific variations. Survival analysis revealed no significant differences in overall survival between H/L and NHW patients, indicating that molecular alterations alone may not fully explain survival disparities and suggesting a role for additional factors such as immune response, environmental exposures, or access to targeted therapies.

This study provides one of the first ethnicity-focused analyses of key oncogenic pathway alterations in HCC, revealing distinct molecular differences between H/L and NHW patients. The findings suggest that RTK/RAS (FGFR4, IGF1R), PI3K (INPP4B), and TGF-beta (TGFBR2) pathway alterations may play a distinct role in HCC among H/L patients, while their prognostic significance in NHW patients remains unclear. These insights emphasize the importance of incorporating ethnicity-specific molecular profiling into precision medicine approaches to improve early detection, targeted therapies, and clinical outcomes in HCC, particularly for underrepresented populations.

Hepatocellular carcinoma (HCC) is a major global health concern, being the sixth most common cancer and the third leading cause of cancer deaths worldwide. Less than 30% of HCC patients are eligible for curative treatment, primarily due to diagnosis at advanced stages. This emphasizes the importance of early detection in improving survival outcomes. In this study, we investigated the methylation levels of certain genes and miRNAs in liquid biopsy and developed a methyl predictive model (MPM-8G). The AUC for MPM-8G was found to be significantly higher than that for AFP (alpha-fetoprotein) alone. When MPM-8G and AFP were combined, the AUC increased notably, indicating that the combined use of MPM-8G and AFP offers superior diagnostic performance and enhances the accuracy of HCC detection. Furthermore, the combination of MPM-8G and AFP proved to be a powerful tool for early diagnosis of HCC. This study successfully identified differences in the methylation levels of certain genes and miRNAs in liquid biopsy from HCC patients, leading to the construction of a predictive model for early diagnosis. The impressive performance of these methylation markers underscores their potential for further clinical application in the management of HCC.

The purpose of this review is to both summarize the current knowledge of hepatocellular carcinoma molecular biology and to suggest a framework in which to prospectively translate this knowledge into patient care. This is timely as recent guidelines recommend increased use of these technologies to advance personalized liver cancer care.

The main themes covered here address germline and somatic genetic alterations recently discovered in hepatocellular carcinoma, largely owing to next generation sequencing technologies, and nascent efforts to translate these into contemporary practice.

Early efforts of translating molecular profiling to hepatocellular carcinoma care demonstrate a growing number of potentially actionable alterations. Still lacking are a consensus on what biomarkers and technologies to adopt, at what scale and cost, and how to integrate them most effectively into care.

Hepatocellular carcinoma (HCC) is one of the most lethal malignancies in the world. Patients with HCC choose postoperative adjuvant transarterial chemoembolization (PA-TACE) after surgical resection to reduce the risk of recurrence. However, many of them have recurrence within a short period.

In this retrospective analysis, a total of 173 patients who underwent PA-TACE between September 2016 and March 2020 were recruited. Radiomic features were derived from the arterial and venous phases of each patient. Early recurrence (ER)-related radiomics features of HCC and the spleen were selected to build two rad-scores using the least absolute shrinkage and selection operator (LASSO) Cox regression analysis. Logistic regression was applied to establish the Radiation (Rad)_score by combining the two regions. We constructed a nomogram containing clinical information and dual-region rad-scores, which was evaluated in terms of discrimination, calibration, and clinical usefulness.

All three radiological scores showed good performance for ER prediction. The combined Rad_score performed the best, with an area under the curve (AUC) of 0.853 (95% confidence interval [CI], 0.783-0.908) in the training set and 0.929 (95% CI, 0.789-0.988) in the validation set. Multivariate analysis identified total bilirubin (TBIL) and the combined Rad_score as independent prognostic factors for ER. The nomogram was found to be clinically valuable, as determined by the decision curves (DCA) and clinical impact curves (CIC).

A multimodal dual-region radiomics model combining HCC and the spleen is an independent prognostic tool for ER. The combination of dual-region radiomics features and clinicopathological factors has a good clinical application value.

Liver cancer is one of the most common malignancies, with severe morbidity and mortality. While considerable progress has been made in liver cancer treatment, the 5-year overall survival (OS) of patients has not improved significantly. Reasons include the inadequate capability of early screening and diagnosis, a high incidence of recurrence and metastasis, a high degree of tumor heterogeneity, and an immunosuppressive tumor microenvironment. Therefore, the identification and validation of specific and robust liver cancer biomarkers are of major importance for early screening, timely diagnosis, accurate prognosis, and the prevention of tumor progression. In this review, we highlight some of the latest research progress and potential applications of liver cancer biomarkers, describing hotspots and prospective directions in biomarker discovery.