New Blood Biomarkers for the Diagnosis of AFP-Negative Hepatocellular Carcinoma

Wang, Ting; Zhang, Kun‐He

doi:10.3389/fonc.2020.01316

Cited by 126 publications

(106 citation statements)

References 174 publications

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“…Thus, AKR1B10 is emerging as a promising biomarker for HCC. In addition to AKR1B10, HSP90α is also a potential serum biomarker for diagnosing α-fetoprotein negative HCC [ 106 ], as it interacts with AKR1B10 [ 66 ].…”

Section: Diseases Associated With Akr1b10 Elevationmentioning

confidence: 99%

The Role of AKR1B10 in Physiology and Pathophysiology

2021

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AKR1B10 is a human nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reductase belonging to the aldo-keto reductase (AKR) 1B subfamily. It catalyzes the reduction of aldehydes, some ketones and quinones, and interacts with acetyl-CoA carboxylase and heat shock protein 90α. The enzyme is highly expressed in epithelial cells of the stomach and intestine, but down-regulated in gastrointestinal cancers and inflammatory bowel diseases. In contrast, AKR1B10 expression is low in other tissues, where the enzyme is upregulated in cancers, as well as in non-alcoholic fatty liver disease and several skin diseases. In addition, the enzyme’s expression is elevated in cancer cells resistant to clinical anti-cancer drugs. Thus, growing evidence supports AKR1B10 as a potential target for diagnosing and treating these diseases. Herein, we reviewed the literature on the roles of AKR1B10 in a healthy gastrointestinal tract, the development and progression of cancers and acquired chemoresistance, in addition to its gene regulation, functions, and inhibitors.

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Section: Diseases Associated With Akr1b10 Elevationmentioning

confidence: 99%

The Role of AKR1B10 in Physiology and Pathophysiology

2021

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“…This finding supports the idea that VAF mean level could serve as a non-invasive surrogate marker reflecting tumor burden. Serum AFP is the most widely used biomarker of HCC both for early diagnosis and evaluation of therapeutic efficacy and prognosis [ 52 ]. On the other hand, there was no correlation between tumor size and serum AFP nor between the change in the sum of the tumor diameters and the kinetics of AFP.…”

Section: Discussionmentioning

confidence: 99%

Identification and monitoring of mutations in circulating cell-free tumor DNA in hepatocellular carcinoma treated with lenvatinib

Fujii

Ono

Hayes

et al. 2021

J Exp Clin Cancer Res

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Background There has been a recent surge in interest in predicting biological effects associated with genomic alterations in order to implement personalized cancer treatment strategies. However, no reports have yet evaluated the utility of profiling blood-based circulating tumor DNA (ctDNA) in hepatocellular carcinoma (HCC) patients treated with lenvatinib (LEN). Method We retrospectively performed ctDNA next-generation sequencing (NGS) analysis in 24 patients with advanced HCC at baseline and 4 weeks after initiation of LEN. Association of the changes in variant allele frequencies (VAFs) during treatment and clinical outcome were evaluated. Results In total, 131 single nucleotide variants, 17 indels, and 23 copy number variations were detected as somatic alterations in 28, 6, and 12 genes, respectively in 23 of 24 patients. The most frequently altered genes were TP53 (54%), CTNNB1 (42%), TERT (42%), ATM (25%), and ARID1A (13%). The reduction in the mean frequency of variants (VAFmean) following 4 weeks of LEN treatment was associated with longer progression-free survival. The specificity and sensitivity of the reduction of VAFmean for predicting partial response were 0.67 and 1.0, respectively, which were higher than those of serum α-fetoprotein level (0.10 and 0.93, respectively). No association between the mutation status at baseline and the effectiveness of LEN was observed. Conclusion Our study demonstrated that somatic alterations could be detected in the majority of advanced HCC patients by ctDNA profiling and that ctDNA-kinetics during LEN treatment was a useful marker of disease progression. These results suggest that ctDNA profiling is a promising method that provides valuable information in clinical practice.

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“…Recently, Wang et al have summarized the novel biomarkers with potential value in the diagnosis of AFPnegative HCC. Numerous glycoproteins have been confirmed to screen AFP-negative liver cancer in clinical studies (44), including Golgi protein 73 (GP73) (45), dickkopf-1 (DKK1) (46), angiopoietin-like protein 2 (ANGPTL2) (47), and haptoglobin (Hp) (48). While few of them have good clinical application value, most of them have not been studied specifically for the diagnosis of AFP-negative hepatocellular carcinoma.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Serum Paraoxonase 1 Using Mass Spectrometry and Lectin Immunoassay in Patients With Alpha-Fetoprotein Negative Hepatocellular Carcinoma

Cao

Shao

et al. 2021

Front. Oncol.

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The diagnosis of AFP (alpha-fetoprotein)-negative HCC (hepatocellular carcinoma) mostly relies on imaging and pathological examinations, and it lacks valuable and practical markers. Protein N-glycosylation is a crucial post-translation modifying process related to many biological functions in an organism. Alteration of N-glycosylation correlates with inflammatory diseases and infectious diseases including hepatocellular carcinoma. Here, serum N-linked intact glycopeptides with molecular weight (MW) of 40–55 kDa were analyzed in a discovery set (n = 40) including AFP-negative HCC and liver cirrhosis (LC) patients using label-free quantification methodology. Quantitative lens culinaris agglutin (LCA) ELISA was further used to confirm the difference of glycosylation on serum PON1 in liver diseases (n = 56). Then, the alteration of site-specific intact N-glycopeptides of PON1 was comprehensively assessed by using Immunoprecipitation (IP) and mass spectrometry based 16O/18O C-terminal labeling quantification method to distinguish AFP-negative HCC from LC patients in a validation set (n = 64). Totally 195 glycopeptides were identified using a dedicated search engine pGlyco. Among them, glycopeptides from APOH, HPT/HPTR, and PON1 were significantly changed in AFP-negative HCC as compared to LC. In addition, the reactivity of PON1 with LCA in HCC patients with negative AFP was significantly elevated than that in cirrhosis patients. The two glycopeptides HAN253WTLTPLK (H5N4S2) and (H5N4S1) corresponding to PON1 were significantly increased in AFP-negative HCC patients, as compared with LC patients. Variations in PON1 glycosylation may be associated with AFP-negative HCC and might be helpful to serve as potential glycomic-based biomarkers to distinguish AFP-negative HCC from cirrhosis.

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New Blood Biomarkers for the Diagnosis of AFP-Negative Hepatocellular Carcinoma

Cited by 126 publications

References 174 publications

The Role of AKR1B10 in Physiology and Pathophysiology

The Role of AKR1B10 in Physiology and Pathophysiology

Identification and monitoring of mutations in circulating cell-free tumor DNA in hepatocellular carcinoma treated with lenvatinib

Analysis of Serum Paraoxonase 1 Using Mass Spectrometry and Lectin Immunoassay in Patients With Alpha-Fetoprotein Negative Hepatocellular Carcinoma

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