Non-Invasive Biomarkers for Immunotherapy in Patients with Hepatocellular Carcinoma: Current Knowledge and Future Perspectives

Abstract

The treatment perspectives of advanced hepatocellular carcinoma (HCC) have deeply changed after the introduction of immunotherapy. The results in responders show improved survival compared with Sorafenib, but only one-third of patients achieve a significant benefit from treatment. As the tumor microenvironment exerts a central role in shaping the response to immunotherapy, the future goal of HCC treatment should be to identify a proxy of the hepatic tissue condition that is easy to use in clinical practice. Therefore, the search for biomarkers that are accurate in predicting prognosis will be the hot topic in the therapeutic management of HCC in the near future. Understanding the mechanisms of resistance to immunotherapy may expand the patient population that will benefit from it, and help researchers to find new combination regimens to improve patients’ outcomes. In this review, we describe the current knowledge on the prognostic non-invasive biomarkers related to treatment with immune checkpoint inhibitors, focusing on serological markers and gut microbiota.

Machine learning and biomarkers in hepatocellular carcinoma: The future is now

“…Thus, scientific debate has arisen regarding the usefulness of returning to the quest for molecular biomarkers for HCC, in particular after the advent of the new immunotherapies. 6,7 In this regard, the article by Brar et al provides a relevant meeting point between using machine learning-based strategies and identifying molecular biomarkers for the management of patients with HCC.…”

“…Although this process may seem straightforward, clinicians struggle daily to solve complex, and sometimes uncertain, diagnoses without having the possibility to rely on molecular data as often happens for other cancers. Thus, scientific debate has arisen regarding the usefulness of returning to the quest for molecular biomarkers for HCC, in particular after the advent of the new immunotherapies 6,7 . In this regard, the article by Brar et al provides a relevant meeting point between using machine learning‐based strategies and identifying molecular biomarkers for the management of patients with HCC.…”

The upregulation of CLGN in hepatocellular carcinoma is potentially regulated by hsa-miR-194-3p and associated with patient progression

“…Currently, systemic therapy for patients with advanced HCC includes molecularly targeted agents, immune checkpoint inhibitors, or a combination of both (2)(3)(4). However, a substantial proportion of patients have yet to benefit from systemic therapy (5,6). Recent studies have identified several novel biomarkers that can predict HCC prognosis.…”

Three molecular subtypes and a five‐gene signature for hepatocellular carcinoma based on m7G‐related classification

“…Discovering biomarkers that can accurately predict HCC prognosis will be a major research topic in the management of HCC treatment in the near future. 10 As one of the most common RNA modifications, N7-methylguanosine (m7G) refers to the RNA methylation of guanine at the N7 position and exists in about 0.4% of guanosine. 11 Great progress has been made in studying the regulation of m7G in cancer.…”

“…Studies have shown that immunotherapy could greatly improve the survival rate of HCC in comparison with sorafenib, but only one‐third of patients benefit significantly from the treatment. Discovering biomarkers that can accurately predict HCC prognosis will be a major research topic in the management of HCC treatment in the near future 10 …”