The Human Cervical Cancer Oncogene Protein Is a Biomarker for Human Hepatocellular Carcinoma

Yoon, Seung Kew; Lim, Nam Kyu; Ha, Seon-Ah; Park, Yong Gyu; Choi, Jong Young; Chung, Kyu Won; Sun, Hee Sik; Choi, Myung Ja; Chung, Junho; Wands, Jack R.; Kim, Jin Woo

doi:10.1158/0008-5472.can-03-3665

Cited by 57 publications

(53 citation statements)

References 30 publications

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“…Moreover, our study showed that AFP level was not correlated with early stage HCC lesions smaller than 3 cm (P=0.1148). This finding is consistent with the conclusions of other studies (27) demonstrating a lack of sensitivity of the AFP serological test when used in the screening for early tumors. While AFP had poor sensitivity in our study, it did show a high specificity for both HCC presence and early HCC in comparison to the low specificity of sCD25 in these analyses.…”

supporting

confidence: 93%

Serum levels of soluble CD25 as a marker for hepatocellular carcinoma

et al. 2012

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Abstract. In a previous study, we showed that the level of soluble CD25 (sCD25) was elevated in a small series of patients with hepatocellular carcinoma (HCC). In the present study, we determined the capacity of serum levels of sCD25 to detect the presence and the early stage of HCC using a larger cohort of HCC patients and evaluated the correlation between sCD25 level and tumor burden. Serum levels of sCD25 were quantified using ELISA in patients with HCC (n=145), controls with advanced fibrosis (n=61) and healthy control subjects (n=30). The levels of sCD25 in patients with HCC (median, 6,955 pg/ml) were significantly higher than those in cirrhosis-only patients (4,310 pg/ml; P<0.0001). At a cut-off value of 2,180 pg/ml, sCD25 had a sensitivity of 92.3% and a specificity of 37.7% in detecting HCC presence [area under the curve (AUC) of 0.685; P<0.0001]. By comparison, α-fetoprotein (AFP) had a sensitivity of 53.8% and a specificity of 86.8% at a cut-off value of 32.8 ng/ml (AUC=0.755; P<0.0001) for HCC presence detection. For early HCC, the sensitivity of sCD25 was 89.6% and its specificity was 39.3% (AUC=0.630; P<0.0001) at a cut-off value of 2,859 pg/ml, while AFP had a sensitivity of 41.7% and a specificity of 82.6% at a cut-off value of 20.6 ng/ml (AUC=0.630; P=0.0257). We also found a significant positive correlation between serum levels of sCD25 and tumor stage. In the present study study, sCD25 was more effective than AFP at detecting the presence and early stages of HCC. This immune factor may hold promise as a novel predictive marker of HCC presence and may be useful in distinguishing early HCC from advanced cirrhosis, currently areas of global unmet need.

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confidence: 93%

Serum levels of soluble CD25 as a marker for hepatocellular carcinoma

et al. 2012

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“…The sensitivity and specificity of serum human cervical cancer oncogene (HCCR) at the cut-off value of 15 µg/mL in detecting HCC are 78.2% and 95.7%, respectively. Moreover, its sensitivities could achieve 76.9% in detecting HCC patients with seronegative for AFP and 69.2% in detecting HCC patients with tumor size less than 2 cm [58] .…”

Section: Genesmentioning

confidence: 99%

Serum tumor markers for detection of hepatocellular carcinoma

Zhou¹

2006

WJG

311

259

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Alpha-fetoprotein and alpha-fetoprotein-L3Alpha fetoprotein (AFP) is a fetal specific glycoprotein produced primarily by the fetal liver. Normally, its serum concentration falls rapidly after birth and its synthesis in adult life is repressed. However, greater than 70% of HCC patients have a high serum concentration of AFP because of the tumor excretion. Forty years after its discovery, serum AFP remains a most useful tumor marker in screening HCC patients. The serum concentration of 20 ng/mL is the most commonly used cut-off value to differentiate HCC patients from healthy adults in clinical researches. However, some investigations have showed that the cut-off value is fluctuant in different ethnic groups. REVIEW Serum tumor markers for detection of hepatocellular carcinoma AbstractHepatocellular carcinoma (HCC) is one of the most frequent malignant tumors and is the second most common cause of cancer death in China. Therefore, it is very important to detect this disease and the recurrence at its earlier period. Serum tumor markers, as the effective method for detecting hepatocellular carcinoma for a long time, could be divided into 4 categories: oncofetal antigens and glycoprotein antigens; enzymes and isoenzymes; genes; and cytokines. Serum alpha fetoprotein (AFP) is the most widely used tumor marker in detecting patients with hepatocellular carcinoma, and has been proven to have capability of prefiguring the prognosis. However, it has been indicated that AFP-L3 and DCP excel AFP in differentiating hepatocellular c a r c i n o m a f r o m n o n m a l i g n a n t h e p a t o p a t h y a n d detecting small hepatocellular carcinoma. Some tumor markers, such as human cervical cancer oncogene and human telomerase reverse transcriptase mRNA, have also been indicated to have higher accuracies than AFP. Furthermore, some other tumor markers, such as glypican-3, gamma-glutamyl transferase II, alpha-lfucosidase, transforming growth factor-beta1, tumorspecific growth factor, have been indicated to be available supplementaries to AFP in the detection. AFP mRNA has been shown to correlate with the metastasis and recurrence of HCC, and it may be the most useful marker to prefigure the prognosis. Some other markers, such as gamma-glutamyl transferase mRNA, vascular endothelial growth factor, and interleukin-8, could also be used as available prognostic indicators, and the simultaneous determination of AFP and these markers may detect the recurrence of HCC at its earlier period.

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“…[3][4][5][6][7] The HCCR gene is classified into the two species HCCR-1 and HCCR-2 according to molecular characteristics. The HCCR2 is an alternative splicing form of HCCR1 and corresponds to amino acids 57-360 of HCCR1.…”

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confidence: 99%

HCCRBP‐1 directly interacting with HCCR‐1 induces tumorigenesis through P53 stabilization

Ha¹,

Shin²,

Lee³

et al. 2007

Intl Journal of Cancer

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Oncogene HCCR-1 functions as a negative regulator of the p53 and contributes to tumorigenesis of various human tissues. HCCR transgenic mice developed breast cancers but it is unknown how HCCR-1 contributes to human tumorigenesis. This study identified a HCCR-1-binding protein 1 (HCCRBP-1) as an HCCR binding partner by performing yeast two hybrid screening. Their endogenous interaction was further confirmed by coimmunoprecipitation experiments. These two proteins colocalized in the mitochondria. HCCRBP-1 was overexpressed in various human tumors. In addition, HCCRBP-1 alone converted NIH/3T3 cells into tumor cells in combination with no other oncogenes. HCCRBP-1 induced tumorigenesis by markedly activating PKC activities but decreasing the pro-apoptotic PKCa and PKCd isoform levels. We observed that p53 stabilization also occurred with functional impairment in HCCRBP-1-transfected 293 cells, as indicated by defective induction of p21, MDM2 and bax. Indeed, HCCRBP-1 decreased p21 promoter activity probably via p53 stabilization leading to the defective function. These results indicate that HCCRBP-1 oncogene induces p53 stabilization and thereby contributes to tumorigenesis. ' 2007 Wiley-Liss, Inc.

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The Human Cervical Cancer Oncogene Protein Is a Biomarker for Human Hepatocellular Carcinoma

Cited by 57 publications

References 30 publications

Serum levels of soluble CD25 as a marker for hepatocellular carcinoma

Serum levels of soluble CD25 as a marker for hepatocellular carcinoma

Serum tumor markers for detection of hepatocellular carcinoma

HCCRBP‐1 directly interacting with HCCR‐1 induces tumorigenesis through P53 stabilization

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