Perspectives on a combined test of multi serum biomarkers in China: Towards screening for and diagnosing hepatocellular carcinoma at an earlier stage

Zhang, Keming; Song, Peipei; Gao, Jianjun; Gaohua, Lu; Zhao, Xin; Zhang, Shaogeng

doi:10.5582/ddt.2014.01026

Cited by 25 publications

(17 citation statements)

References 68 publications

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“…The YAP1-TEAD complex activates numerous growth-related genes in HCC [27]. Accordingly, we found a significant positive correlation of YAP1 and YAP1-TEAD levels with the expression of the proliferation marker Ki67, and the progression markers CTGF [28, 29] and MDK [19, 20], in HCC.…”

Section: Discussionmentioning

confidence: 62%

“…No significant differences between the two groups occurred as concerns patients' sex, etiology, presence of cirrhotic liver, and Edmondson-Steiner grade. Significantly higher tumor size, alpha-fetoprotein secretion, proliferation index (Ki67 expression), YAP1 expression, and Midkine expression (as index of poor differentiation), [19, 20], were found in HCCP than in HCCB.…”

Section: Resultsmentioning

confidence: 99%

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Post-translational deregulation of YAP1 is genetically controlled in rat liver cancer and determines the fate and stem-like behavior of the human disease

et al. 2016

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Previous studies showed that YAP1 is over-expressed in hepatocellular carcinoma (HCC). Here we observed higher expression of Yap1/Ctgf axis in dysplastic nodules and HCC chemically-induced in F344 rats, genetically susceptible to hepatocarcinogenesis, than in lesions induced in resistant BN rats. In BN rats, highest increase in Yap1-tyr357, p73 phosphorylation and Caspase 3 cleavage occurred. In human HCCs with poorer prognosis (< 3 years survival after partial liver resection, HCCP), levels of YAP1, CTGF, 14–3–3, and TEAD proteins, and YAP1-14-3-3 and YAP1-TEAD complexes were higher than in HCCs with better outcome (> 3 years survival; HCCB). In the latter, higher levels of phosphorylated YAP1-ser127, YAP1-tyr357 and p73, YAP1 ubiquitination, and Caspase 3 cleavage occurred. Expression of stemness markers NANOG, OCT-3/4, and CD133 were highest in HCCP and correlated with YAP1 and YAP1-TEAD levels. In HepG2, Huh7, and Hep3B cells, forced YAP1 over-expression led to stem cell markers expression and increased cell viability, whereas inhibition of YAP1 expression by specific siRNA, or transfection of mutant YAP1 which does not bind to TEAD, induced opposite alterations. These changes were associated, in Huh7 cells transfected with YAP1 or YAP1 siRNA, with stimulation or inhibition of cell migration and invasivity, respectively. Furthermore, transcriptome analysis showed that YAP1 transfection in Huh7 cells induces over-expression of genes involved in tumor stemness. In conclusion, Yap1 post-translational modifications favoring its ubiquitination and apoptosis characterize HCC with better prognosis, whereas conditions favoring the formation of YAP1-TEAD complexes are associated with aggressiveness and acquisition of stemness features by HCC cells.

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Section: Discussionmentioning

confidence: 62%

Section: Resultsmentioning

confidence: 99%

Post-translational deregulation of YAP1 is genetically controlled in rat liver cancer and determines the fate and stem-like behavior of the human disease

et al. 2016

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“…Moreover, HCC occurring in China accounts for at least half of the new cases worldwide each year. Hence, there is an urgent demand for optimal serum biomarkers to help improve the early diagnosis of HCC [ 28 ]. Unfortunately, few studies have focused on the Chinese population, and these studies have also involved a small sample size and limited number of controls [ 17 , 18 ].…”

Section: Discussionmentioning

confidence: 99%

Des-γ-Carboxyprothrombin Plasma Level in Diagnosis of Hepatocellular Carcinoma in a Chinese Population Undergoing Surgery

et al. 2016

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BackgroundThe usefulness of Des-γ-carboxyprothrombin (DCP) has been indicated in areas where hepatitis C virus is prevalent. DCP has yet to be used in China. The aim of this study was to evaluate the usefulness of DCP in Chinese patients with hepatocellular carcinoma (HCC) predominantly caused by hepatitis B.Material/Methods329 subjects with HCC and 371 subjects without HCC that all underwent surgery were consecutively enrolled. Serum AFP and plasma DCP levels in all subjects and 153 healthy volunteers were measured and analyzed.ResultsOf 329 subjects with HCC, 258 (78.4%) were HBsAg positive. The median level of plasma DCP was 853.72 mAU/mL in subjects with HCC, 26.43 mAU/mL in subjects without HCC, and 29.91 m AU/mL in healthy volunteers. A cut-off DCP value of 87 mAU/mL yielded the optimal sensitivity of 74.80% and a specificity of 83.33% for differentiating subjects with HCC from subjects without HCC. The combination of AFP of 21.33 ng/mL and DCP of 87 mAU/mL had a sensitivity of 82.60% for tumors no larger than 2 cm, as well as a sensitivity of 90% for tumors larger than 5 cm.ConclusionsThe combination of DCP and AFP yielded great improvement in sensitivity in differentiating subjects with HCC from subjects without HCC. These two markers may be incorporated in the protocol for surveillance and diagnosis of HCC in the high-risk Chinese population.

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“…Therefore, long since GGT was not utilized as an (29,(36)(37)(38)(39)(40). The combination of GGT and other indicators, such as tumor size, tumor number, MVI, or laboratory data for AFP and DCP, should be paid more attention when deciding a treatment and predicting the curative results for patients with HCC (41).…”

Section: Ggt As a Predictive Biomarker In Clinical Investigationsmentioning

confidence: 99%

Advances of diagnostic and mechanistic studies of γ-glutamyl transpeptidase in hepatocellular carcinoma

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Song

Sun

et al. 2016

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Perspectives on a combined test of multi serum biomarkers in China: Towards screening for and diagnosing hepatocellular carcinoma at an earlier stage

Cited by 25 publications

References 68 publications

Post-translational deregulation of YAP1 is genetically controlled in rat liver cancer and determines the fate and stem-like behavior of the human disease

Post-translational deregulation of YAP1 is genetically controlled in rat liver cancer and determines the fate and stem-like behavior of the human disease

Des-γ-Carboxyprothrombin Plasma Level in Diagnosis of Hepatocellular Carcinoma in a Chinese Population Undergoing Surgery

Advances of diagnostic and mechanistic studies of γ-glutamyl transpeptidase in hepatocellular carcinoma

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