Biomarker development for hepatocellular carcinoma early detection: current and future perspectives

Abstract

Early detection of hepatocellular carcinoma (HCC) leads to improved survival; however, current early detection strategies for HCC surveillance are ineffective. Thus, there has been interest in developing biomarkers to aid in the early detection HCC. In this review, we discuss the five phases of biomarker discovery that are necessary for clinical implementation. We also describe the most promising investigational biomarkers and their phase of discovery. We review several promising technologies for the early detection of HCC, including miRNA, metabolomics and proteomics. Promisingly, there are samples from multiple longitudinal cohorts of patients with cirrhosis in the USA that are being collected in order to validate candidate biomarkers for HCC. A biomarker-based strategy has the potential to become the primary surveillance method for HCC detection.

Identification of novel biomarkers of hepatocellular carcinoma by high‐definition mass spectrometry: Ultrahigh‐performance liquid chromatography quadrupole time‐of‐flight mass spectrometry and desorption electrospray ionization mass spectrometry imaging

“…52 Therefore, the combination of several molecules is necessary to improve the sensitivity and specificity for the early diagnosis of HCC. 38 In this study, we demonstrated the difference in TG species in HCC tissue. However, it is still necessary to evaluate the correlation with the plasma concentration of TGs and reproducibility as a candidate biomarker with increased sample numbers.…”

“…However, the sensitivity decreases to approximately 40% for the detection of small tumors . Therefore, the combination of several molecules is necessary to improve the sensitivity and specificity for the early diagnosis of HCC . In this study, we demonstrated the difference in TG species in HCC tissue.…”

“…Several candidates for HCC biomarkers currently exist; however, most have not been identified through the requisite phases of biomarker development, and there is a lack of clear data regarding the selection of optimum agents for individual patients . Therefore, novel biomarkers are needed to enable early diagnosis and personalized therapy for HCC, and it is necessary to study the function of molecules that can predict disease progression or prognosis to improve clinical outcomes …”

Recent advances in liver transplantation for cancer: The future of transplant oncology

“…MacParland et al using single-cell RNA techniques have shown that there are at least 2 different types of immune cells in the liver, and this may be key for HCC-directed therapies. 41 Different authors have published a wide range of possible biomarkers in HCC diagnosis and surveillance, such as osteopontin, 42 GALAD score and BALAD-2, 43 midkine, 44 DCP, lectin-bound alphafetoprotein (or AFP-L3), 45 Dickkopf-1, glypcan-3, HCCR, alpha-L-fucosidase, 46,47 golgi protein-73, squamous-cell carcinoma antigen (or SCC-IgM), 48,49 micro-RNA, kininogen, 50,51 metabolomics, proteomics, 52,53 circulating tumour cells and cell-free DNA, 54 polo-like kinase genes, PD-1 (programmed cell death protein 1) and TIM-3 (T-cell immunoglobulin and mucin-domain containing-3). 55,56 Most of this research has not been done in the transplant population.…”

Implementation of Clinical Proteomics: A Step Closer to Personalized Medicine?

“…The latter mirrors the main consideration that, per definition, success of a clinical –omics study is ultimately defined based on clinical implementation. Along these lines, the steps ensuing biomarker discovery have been described not only in the form of general principles, but also as applied to specific diseases or groups of diseases (such as neuronal diseases, hepatocellular carcinoma, protein aggregation diseases, and others).…”