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Guoxin Zhang,
Seon-Ah Ha,
Hyun K Kim,
Jinah Yoo,
Sanghee Kim,
Youn S Lee,
Soo Y Hur,
Yong W Kim,
Tae E Kim,
Yong G Park, [......], Yang Yang,
Zekuan Xu,
Eun Y Song,
Zuhu Huang,
Peng Jirun,
Jin Zhongtian,
Qiao Shishi,
Cui Zhuqingqing,
Gong Lei,
Jin W Kim
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ABSTRACT: Hepatocellular carcinoma (HCC) is one of the most frequent malignant tumors in the world. The only serological marker widely used for the diagnosis of HCC is alpha-fetoprotein (AFP). Despite that AFP is widely used for the diagnosis of HCC, it has a limit as a serological marker due to its low sensitivity and specificity. The human cervical cancer proto-oncogene 1 (HCCR-1) was previously reported as a new biomarker for HCC. To further evaluate the HCCR-1 as a biomarker for HCC, we conducted the prospective cohort study. We evaluated the significance of simultaneous measurement of 2 tumor markers in the diagnosis of HCC in China, Japan and Korea. Two markers for HCC, AFP and HCCR-1, were measured in the sera obtained from 1,338 patients at the time of initial diagnosis of HCC. Of the 1338 HCC patients, 616 (46%) and 686 (51.3%) were sero-positive for AFP and HCCR-1, respectively. The positive rate for HCC was increased up to 74.1% in combined use of AFP and HCCR-1. Many cases (54%) for AFP-negative HCC were positive for HCCR-1 and vice versa. More importantly, the diagnostic rate for small HCC (< 2 cm) was significantly improved in the combined analysis of AFP and HCCR-1 to 56.9% although it was only 40.1% and 23.4% in the single analysis of HCCR-1 and AFP, respectively. Our result suggests that the HCCR-1 could be an useful biomarker for HCC while the diagnostic rate could be significantly improved in the combined use of HCCR-1 and AFP.
Disease markers 01/2012; 32(4):265-71. · 1.64 Impact Factor
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Peng Jirun,
Guoxin Zhang,
Hyun Kee Kim,
Seon-Ah Ha,
Jin Zhongtian,
Qiao Shishi,
Cui Zhuqingqing,
Gong Lei,
Jinah Yoo,
Sanghee Kim,
Yong Gyu Park,
Jing Wang, Yang Yang,
Zekuan Xu,
Zuhu Huang,
Yun Kyung Lee,
Eun Young Song,
Jin Woo Kim
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ABSTRACT: Serum alpha fetoprotein (AFP) is the most widely used tumor marker in detecting patients with hepatocellular carcinoma (HCC). However, it has been indicated that HCCR-1 (human cervical cancer oncogene 1) might be supplementary to AFP in the detection. We conducted a prospective study in 120 normal and 524 liver disease patients to evaluate the significance of simultaneous measurement of 2 tumor markers (AFP and HCCR-1) in the diagnosis of HCC through the cohort study in Korea and China. We also performed immunohistochemical studies using 25 normal subjects (N), 32 liver cirrhosis (LC) and 116 HCC tissues. The sensitivities of AFP (20 ng/mL) and HCCR-1 (10 ng/mL) in HCC were 55.8% (164/294) and 44.2% (130/294), respectively. When AFP was combined with HCCR-1, sensitivities increased to 4.2% (N), 12.7% (chronic hepatitis; CH), 50.0% (LC), and 77.2% (HCC), respectively. Although there was no significant difference in the diagnostic rate for HCC between AFP and HCCR-1, many cases for AFP-negative HCC were positive for HCCR-1 and vice versa. Moreover, the combined use of AFP and HCCR-1 improved the diagnostic rate to 70.8% in small HCC (< 2 cm) and 81.6% in large HCC (⩾ 2 cm), respectively. AFP and HCCR-1 are independent markers. Our result suggests that the HCCR-1 could be an useful biomarker for HCC while the diagnostic rate could be significantly improved in the combined use of HCCR-1 and AFP.
Disease markers 01/2011; 30(6):307-15. · 1.64 Impact Factor
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ABSTRACT: Human cervical cancer oncoprotein 1 (HCCR-1), reported as a negative regulator of p53, is over-expressed in a variety of human cancers. However, it is yet unknown whether HCCR-1 plays any role in pancreatic cancer development. The aim of this study was to investigate the effect of epidermal growth factor on the expression of HCCR in pancreatic cancer cells, and to explore if PI3K/Akt/mTOR signaling pathway mediated this expression.
A polyclonal antibody against HCCR protein was raised by immunizing Balb/c mice with the purified recombinant protein pMBPc-HCCR. Tissue samples were constructed on a tissue chip, and the expression of HCCR was investigated by immunohistochemistry assay and Western blotting. Pancreatic cell line, PANC-1 cells were stably transfected with plasmids containing sense-HCCR-1 fragment and HCCR siRNA fragment. MTT and transwell assay were used to investigate the proliferation and invasion of stable tansfectants. The specific inhibitor of PI3K and mTOR was used to see if PI3K/mTOR signal transduction was involved in the induction of HCCR gene expression. A Luciferase assay was used to see if Akt can enhance the HCCR promoter activity.
HCCR was up-regulated in pancreatic tumor tissues (mean Allred score 4.51+/-1.549 vs. 2.87+/-2.193, P<0.01), especially with high expression in poorly differentiated pancreatic cancer. The growth of cells decreased in HCCR-1 siRNA transfected cells compared with vector transfectants. The number of invasion cells was significantly lower in HCCR-1 siRNA transfected cells (24.4+/-9.9) than that in vector transfectants (49.1+/-15.4). Treatment of PANC-1 cells with epidermal growth factor increased HCCR protein level in a dose- and time-dependent manner. However, application of LY294002 and rapamycin caused a dramatic reduction of epidermal growth factor-induced HCCR expression. Over-expression of exogenous constitutively active Akt increased the HCCR promoter activity; in contrast, dominant negative Akt decreased the promoter activity.
EGF-induced HCCR-1 over-expression is mediated by PI3K/AKT/mTOR signaling which plays a pivotal role in pancreatic tumor progression, suggesting that HCCR-1 could be a potential target for cancer therapeutics.
BMC Cancer 01/2010; 10:161. · 3.01 Impact Factor
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ABSTRACT: MDM2 is a major negative regulator of p53, and a single nucleotide polymorphism (SNP) in the MDM2 promoter region SNP309 (rs2279744) has been shown to increase the affinity of the transcriptional activator Sp1, resulting in elevated MDM2 transcription and expression in some cancers. The aim of this study was to determine whether SNP309 is associated with susceptibility to gastric cancer in Chinese patients.
Two hundred and sixty patients with gastric cancer and 260 healthy controls were genotyped for MDM2 SNP309 using the PCR-RFLP method. Helicobacter pylori's infection status was determined using a validated serology test.
The healthy control group was found to be in Hard-Weinberg equilibrium at the polymorphic loci studied (chi(2) = 3.63, p = 0.06). Multiple logistic regression analyses revealed that the risk of gastric cancer for SNP309 (G/G) was significantly increased when compared with T carriers (adjusted odds ratio (OR): 2.05, 95% confidence interval (CI): 1.31-3.20). Further stratification analyses based on the recessive models reveal that a significantly increased risk of gastric cancer associated with the GG genotype was evident among subjects with H. pylori infection (adjusted OR: 2.52, 95% CI: 1.45-4.37), and noncardia gastric cancer patients (adjusted OR: 2.29, 95% CI: 1.41-3.71), compared with the T carriers. When stratified by histologic subtype of gastric cancer, the risk was also statistically significant. There was no significant difference in age at diagnosis among genotypes.
The MDM2 promoter SNP309 is associated with the presence of gastric cancer in Chinese patients especially those with H. pylori infection.
Helicobacter 10/2009; 14(5):114-9. · 3.15 Impact Factor
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ABSTRACT: Development of an accurate and less cumbersome noninvasive method to detect current Helicobacter pylori infection is essential in clinic. The aim of this study was to evaluate the performance of the CIM test, also known as the Assure H. pylori Rapid Test (Genelabs Diagnostics Pty. Ltd., Singapore), for the diagnosis of current H. pylori infection before and after eradication therapy in Chinese population.
A total of 452 eligible people were recruited for this study in Jiangsu Province, China. Each individual underwent a 13C urea breath test (13C-UBT). For the evaluation of CIM test after eradication, 115 H. pylori-positive outpatients were treated with 1-week triple therapy. One month after the end of therapy, the patients underwent 13C-UBT again, and the CIM-test was performed 1, 3, and 6 months after the end of therapy. Its performance (sensitivity, specificity, positive and negative predictive values, and accuracy) were determined using the 13C-UBT as a gold standard for H. pylori diagnosis.
H. pylori was detected in 221 (65.6%) of the 337 people by 13C-UBT. The sensitivity, specificity, positive and negative predictive values, and accuracy of the CIM test were 93.2%, 90.5%, 94.9%, 87.5%, and 92.3%, respectively, using 13C-UBT as a gold standard. One month after eradication therapy, the sensitivity, specificity of CIM test were only 50% and 66.7%, 66.7% and 84.6% 3-month after eradication therapy and the sensitivity, specificity increased to 85.7% and 96.9%, respectively, when CIM test was used 6 months after the end of anti-H. pylori therapy.
The CIM test is a simple, rapid, accurate, cheap, and near-people test. It may be satisfactory for detecting H. pylori infection in cases without eradication therapy, but it could not differentiate the past or current infection correctly within 6 months after anti-H. pylori therapy.
Helicobacter 03/2008; 13(1):49-55. · 3.15 Impact Factor
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Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology 04/2007; 15(3):223-4.
