Risk Factors of Hepatocellular Carcinoma for Precision Personalized Care

Fujiwara, Naoto; Liu, Po Hong; Athuluri-Divakar, Sai Krishna; Zhu, Shijia; Hoshida, Yujin

doi:10.1007/978-3-030-21540-8_1

Cited by 10 publications

(12 citation statements)

References 150 publications

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“…HCC withdismal prognosis has brought great burdens for public health worldwide although the various prevalence of underlying risk factors in different areas 11,12 . Once discovered, a great deal of HCC patients have missed the best opportunity for surgical resection, following that 70% patients undertake recurrence within 5 years .…”

Section: Discussionmentioning

confidence: 99%

KRT23 Acts as an Oncogene in Hepatocellular Carcinoma by Regulating P21 via PI3K/AKT/GSK3β Pathway

Guo¹,

Ma²,

Wang³

et al. 2020

Preprint

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Background:Hepatocellular carcinoma (HCC) is a leading cancer worldwide for which diagnosis, treatment and progression are largely unknown. Keratin23 is a potential biomarker forHCC development; however, regulatory mechanisms underlying its expression remain unclear. Inthis research we explored the expression and effect of KRT23 underlying HCC development. Materials and methods:GEPIA was applied to analyze the expression of KRT23 in HCC samples and Kaplan-Merier survival analysis for patients’ prognosis. Next, IHC was further conducted for confirming its expression in HCC tissues. Meanwhile qRT-PCR and western blot analysis were applied to examine the expression of KRT23 on both mRNA and protein level in HCC cell lines compared with immortal hepatocyte LO2. Cell experiments including MTT assay, apoptosis analysis, cell cycle assay and clone formation assay were conducted for cell proliferation while transwell assay and scratch test for metastasis in vitro. Moreover, xenograft tumors in nude mice were further conducted for verification in vivo. As for mechanism in depth, immunofluorescence and western blot were operated to explore the effect of KRT23 on EMT and PI3K/AKT/GSK3βsignaling pathway. Furthermore, Co-immunoprecipitation was applied for interaction between KRT23 and P21. Functional rescue experiments were conducted to further testify their mutual effect.Results:For this research, we discovered the high expression of KRT23 in HCC samples and cell lines. Functionally, KRT23 knockdown reduced cell proliferation and metastasis in vitro and vivo. Furthermore, KRT23 participated in EMT progression and interacted with P21 to mediate PI3K/AKT/GSK3βpathway in HCC development.Conclusion:To summarize, KRT23 accelerated HCC proliferation and metastasis by regulating P21 via PI3K/AKT/GSK3βpathway.

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Section: Discussionmentioning

confidence: 99%

KRT23 Acts as an Oncogene in Hepatocellular Carcinoma by Regulating P21 via PI3K/AKT/GSK3β Pathway

Guo¹,

Ma²,

Wang³

et al. 2020

Preprint

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“…Fourth, for its dynamic change over time, the time series PLSec assessment warrants future evaluation in larger cohorts to further understanding of the natural history of chronic liver disease and response to therapeutic intervention. Finally, we leveraged the PRoBE design with archived specimens 35 ; therefore, other potential risk stratification variables/biomarkers were not available for comparison.…”

Section: Limitations Of Studymentioning

confidence: 99%

“…Subsequently, we developed a composite score with other clinical variables associated with HCC risk, which was further validated in two independent cohorts (validation set 2 [nested case-control series] and 3 [cohort study]) (Figure 1; Table 1), utilizing a prospective specimen collection, retrospective blinded evaluation (PRoBE) design. 35 HCC was diagnosed based on histological or imaging-based examinations according to practice guidelines. 4,55 Validation set 1 (prospective-retrospective cohort): A total of 331 cirrhosis patients with mixed etiologies were consecutively and prospectively enrolled at University of Michigan between January 2004 and September 2006, and regularly followed up using ultrasonography with AFP every 6 months for incident HCC for a median of 4.5 years (IQR, 1.9-11.4 years).…”

Section: Patients For Validation Of Plsec and A Construction Of Plsec-afpmentioning

confidence: 99%

A blood-based prognostic liver secretome signature and long-term hepatocellular carcinoma risk in advanced liver fibrosis

Fujiwara

Kobayashi

Fobar

et al. 2021

Med

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“…Patients with LC are at a high risk for developing hepatocellular carcinoma (HCC) [ 49 ]. Carnitine might exert preventive effects on HCC development, because it has anti-inflammatory and antioxidant properties, which are both critical mechanisms of cancer prevention [ 50 ].…”

Section: Carnitine and Hepatocellular Carcinomamentioning

confidence: 99%

Usefulness of Carnitine Supplementation for the Complications of Liver Cirrhosis

et al. 2020

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Carnitine is a vitamin-like substance that regulates lipid metabolism and energy production. Carnitine homeostasis is mainly regulated by dietary intake and biosynthesis in the organs, including the skeletal muscle and the liver. Therefore, liver cirrhotic patients with reduced food intake, malnutrition, biosynthetic disorder, and poor storage capacity of carnitine in the skeletal muscle and liver are more likely to experience carnitine deficiency. In particular, liver cirrhotic patients with sarcopenia are at a high risk for developing carnitine deficiency. Carnitine deficiency impairs the important metabolic processes of the liver, such as gluconeogenesis, fatty acid metabolism, albumin biosynthesis, and ammonia detoxification by the urea cycle, and causes hypoalbuminemia and hyperammonemia. Carnitine deficiency should be suspected in liver cirrhotic patients with severe malaise, hepatic encephalopathy, sarcopenia, muscle cramps, and so on. Importantly, the blood carnitine level does not always decrease in patients with liver cirrhosis, and it sometimes exceeds the normal level. Therefore, patients with liver cirrhosis should be treated as if they are in a state of relative carnitine deficiency at the liver, skeletal muscle, and mitochondrial levels, even if the blood carnitine level is not decreased. Recent clinical trials have revealed the effectiveness of carnitine supplementation for the complications of liver cirrhosis, such as hepatic encephalopathy, sarcopenia, and muscle cramps. In conclusion, carnitine deficiency is not always rare in liver cirrhosis, and it requires constant attention in the daily medical care of this disease. Carnitine supplementation might be an important strategy for improving the quality of life of patients with liver cirrhosis.

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Risk Factors of Hepatocellular Carcinoma for Precision Personalized Care

Cited by 10 publications

References 150 publications

KRT23 Acts as an Oncogene in Hepatocellular Carcinoma by Regulating P21 via PI3K/AKT/GSK3β Pathway

KRT23 Acts as an Oncogene in Hepatocellular Carcinoma by Regulating P21 via PI3K/AKT/GSK3β Pathway

A blood-based prognostic liver secretome signature and long-term hepatocellular carcinoma risk in advanced liver fibrosis

Usefulness of Carnitine Supplementation for the Complications of Liver Cirrhosis

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