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- Increased GP73 expression in hepatocellular carcinoma tissue correlates with tumor aggression but not survival(发表在《Journal of Gastroenterology and Hepatology》)
- 作者:毛一雷|发布时间:2011-04-07|浏览量:1188次
Increased GP-73 expression in hepatocellular carcinoma tissue correlates with tumor aggression but not survival
P73 Running Head: GP73 correlates with tumor aggression but not survival
Yongliang Sun,* Huayu Yang,* Yilei Mao,* Haifeng Xu,* Jinchun Zhang,* Guangbing Li,* Xin Lu,* Xinting Sang,* Haitao Zhao,* Shouxian Zhong,* Jiefu Huang,* and Hongbing Zhang†
*Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital and
†National Key Laboratory of Basic Medical Sciences, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & PUMC, Beijing, China
Yongliang Sun and Huayu Yang contributed equally to this article.
Correspondence
Yilei Mao, MD, PhD,
Department of Liver Surgery, Peking Union Medical College Hospital
1 Shuai-fu-yuan, Dongcheng District, Beijing, China 100730
Tel: +86-130 110 79603 or +86-10-6529 6042;
Fax: +86-10-6529 6043;
E-mail: dolphinyahy@hotmail.com or maoy@public3.bta.net.cn,
Abstract
Background and Aim: Serum Golgi protein 73 (sGP73) is a novel and promising biomarker for hepatocellular carcinoma (HCC). However, there are few reports on the pattern of GP73 expression in HCC and the relationship of this expression to clinicopathologic features of patients. This study aimed to investigate the expression of GP73 and it correlation with clinical parameters.
Methods: We examined GP73 expression in HCC and adjacent paracarcinomatous liver (PCL) tissue in 36 HCC patients, and took 14 normal liver (NL) samples from hepatic hemangioma patients. Western blot analysis and quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) were used for analyses.
Results: GP73 expression in HCC was significantly higher than in the corresponding PCL and NL samples at both protein and mRNA levels (P<0.001). The elevated level of GP73 protein was strongly associated with tumor size, vein invasion, and tumor differentiation, suggesting augmented tumor invasion and metastasis. However, there was no association between GP73 expression and patient survival.
Conclusion: Significant overexpression of GP73 at both protein and mRNA levels along with overexpression of GP73 protein is associated with aggressive behavior of HCC, but not overall patient survival. Further research is needed to determine the potential of GP73 as a therapeutic target.
Keywords: hepatocellular carcinoma, Golgi Protein 73, tumor progression, clinicopathologic correlation
Introduction
Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third most common cause of cancer-related deaths worldwide. It imposes high social and medical burdens, especially in societies with a high incidence of viral hepatitis infection.1-5 The overall prognosis of HCC is poor, with a 5-year survival rate of 3-5% after initial diagnosis. This is largely due to the difficulties of early diagnosis.
Recent advances in proteomics have identified a group of novel HCC serum tumor markers that might enable early detection of HCC. Several studies indicate that Golgi protein 73 (GP73) is one of the most promising serum markers for HCC.6-8 Our previous clinical trial in over 4,000 subjects and fully comparisons has showed advantages of using serum GP73 (sGP73) in diagnose of HCC over alpha-fetoprotein (AFP). It also first ever indicated a significant decrease in serum GP73 after surgical removal of the tumor, with a subsequent increase after HCC recurrence.6
However, the majority of studies on GP73 have been on the detection of sGP73 as a tumor marker,9-12 while the exact mechanism of elevated GP73 and tumorigenesis remains largely unknown.13 The few studies that have investigated GP73 expression pattern in liver tissues have been mainly confined to immunohistochemistry.14-17 The immunohistochemical method is mostly used to localize protein expression sites, and its effectiveness as a semiquantitative method can be influenced by many factors.
Investigation of GP73 expression in HCC tissues might improve understanding of the biological role and biochemical function of GP73 as well as hepatocarcinogenesis on molecular and genetic levels.
To the best of our knowledge, this is the first study to examine GP73 expression at mRNA and protein levels in HCC tissues using quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) and western blot methods. In the present study, we analyzed GP73 expression at mRNA and protein levels in HCC, paracarcinomatous liver (PCL) tissue, and normal liver (NL) from excised specimens of HCC or hepatic hemangioma patients. Our aim was to investigate its expression pattern and correlations with clinicopathologic parameters, including patient survival.
Methods
Patients and samples
HCC and matched paracarcinomatous liver specimens from 36 HCC patients and normal liver samples from 14 hepatic hemangioma patients (controls) were collected in the operating room, and immediately frozen in liquid nitrogen. They were then stored at -80º C until further testing. Paracarcinomatous tissue was defined as liver tissue collected 2-5cm away from the tumor border.
All patients were treated in the Department of Liver Surgery, Peking Union Medical College Hospital, between September 2003 and January 2009. A 2ml blood sample was drawn from each subject, then spun and aliquoted. Samples were stored at -80ºC until further testing. All blood samples from HCC patients were drawn prior to the initiation of treatment. Diagnoses were confirmed by pathological examination. The study protocol was approved by the Ethics Committee of the Peking Union Medical College Hospital. Informed consent was obtained from each patient.
We recorded clinicopathologic parameters, including age, gender, liver function, hepatitis B virus (HBV) infection, AFP level, tumor size, number of tumor nodules, histopathological classification, vein invasion, recurrence status, and patient survival time. Vein invasion found during pathological examination indicated tumor infiltration in the portal venous and/or hepatic veins (Fig. 1). We monitored recurrence with ultrasound, CT scan, and MRI. We also used hepatic arteriography, which showed typical tumor staining during adjuvant treatment of transarterial chemoembolization (TACE).
Western Blot Analysis
Total protein was extracted from HCC, PCL, and NL tissues with lysis buffer (Dingduo, Beijing, China) using an SDT Tissumizer (Kimble, Vineland, NJ, USA). Lysates were centrifuged at 13,000 rpm at 4°C for 3 minutes. Supernatants were stored at -80°C, and subsequently analyzed in batch fashion. We determined protein concentration in the supernatants using a modified bicinchoninic acid (BCA) protein assay kit (Dingduo, Beijing, China), employing bovine serum albumin as a standard.
Aliquots of 30μg of total tissue protein or 1μl serum were subjected to SDS-polyacrylamide gel electrophoresis on 4-12% Novex Bis-Tris precasting gels (Invitrogen, Carlsbad, CA, USA). Gels were run at 100V for 70mins. A lane containing 1μl of serum from a healthy subject was also included in each gel. Separated protein was then transferred onto nitrocellulose membranes with a 6.5-minute iBlot Dry Blotting System (Invitrogen, Carlsbad, CA, USA). Membranes were kept for 1h in blocking buffer (3% BSA in TBST). After blocking, the blots were incubated with goat anti-GP73 polyclonal antibody (Santa Cruz Biotechnology, Santa Cruz, CA, USA) diluted at 1:800. After washing (TBST), the membranes were incubated with a 1:20000 dilution of horseradish peroxidase conjugated mouse anti-goat secondary antibody (Santa Cruz Biotechnology, Santa Cruz, CA, USA). Glyceraldehyde phosphate dehydrogenase (GAPDH) was also determined by using the specific antibody (Santa Cruz Biotechnology, Santa Cruz, CA, USA) as a loading control. After washing, the blots were developed using the ECL Plus chemiluminescent detection system (Thermo, Rockford, IL, USA). We performed densitometric analysis of the immunoblots to quantify the amounts of GP73 protein. GP73 specific signals were quantified from X-ray films using a scanner with BandScan 4.30 densitometry software, and expressed as integrated intensity units relative to the GP73 signal detected in serum from healthy controls.
To assess the reproducibility of the assay, all samples were tested in triplicate, and GP73 concentration was calculated as the mean of triplicate determinations for each serum and protein extraction from tissue samples. There was < 10% variation in sample-to-sample analysis.
Quantitative real-time reverse transcriptase-polymerase chain reaction
Total RNA was extracted from frozen tissue specimens (30-50 mg) using Trizol reagent (Invitrogen, Carlsbad, CA, USA) according to the instructions provided by the manufacturer, and RNase-free DNase was used to remove DNA contamination. The quality of RNA was determined by agarose gel analysis, and the RNA concentration was measured with a Nanodrop ND-2000 spectrophotometer (Thermo, Rockford, IL, USA).
cDNA was synthesized from RNA, using Superscript III (Invitrogen, Carlsbad, CA, USA) according to the manufacturer’s protocol and under the following condition: 65°C for 5 minutes, 50°C for 50 minutes, 85°C for 5 minutes, 37°C for 20 minutes. cDNA was stored at -20ºC until further analysis.
GP73 and Tata-binding protein (TBP) gene were used as the target and internal loading control genes. We used 96- microwell plates in an ABI 7900 Real-Time PCR System (Applied Biosystems, Carlsbad, CA, USA) to carry out qRT-PCR. All samples were run in triplicate. qRT-PCR amplification was conducted in a 20μl reaction using ABI TaqMan Gene Expression Master Mix (Applied Biosystems, Carlsbad, CA, USA). GP73 and TBP specific assays (Applied Biosystems, Carlsbad, CA, USA) were used to detect mRNA expression in HCC, PCL and NL tissues (GP73 assay ID: Hs00213061-m1; TBP assay ID: Hs00427620-m1). The reaction was initiated by activation of AmpErase UNG and AmpliTaq Gold DNA polymerase at 50°C for 2 min, 95°C for 10 min, followed by 40 cycles at 95°Cfor 15 s and 60°C for 1min. Data were normalized using the TBP housekeeping gene and were expressed as 2-ΔΔCt. The 10μl amplification products were separated by electrophoresis on 2% agarose gels and visualized by ethidium bromide staining to confirm the amplification products. The expected size of GP73 is a 400-base-pair fragment.
Patient follow-up
We obtained follow-up data after liver resection by direct communication with the patients or their relatives, or review of the hospital records for all 36 HCC patients. The follow-up period was defined as the time from the date of surgery to the date of patient death or the last follow-up point. Deaths from other causes were treated as censored cases.
Statistical methods
Quantitative values were presented as mean ±SD or median (range, 25th and 75th percentiles). The Mann-Whitney U test was used to compare GP73 protein and mRNA expression between HCC, PCL, or NL tissue. Spearman correlation coefficients were used to analyze the relations between expression levels of GP73 protein and mRNA in HCC, GP73 protein level in HCC, and sGP73 in the serum. Fisher’s exact and chi-squared tests were used to analyze the correlation between GP73 expression level and clinicopathologic parameters in patients with HCC. Bivariate correlations were used to analyze the association between survival time and GP73 protein, GP73 mRNA, and sGP73. All tests were two-tailed and P<0.05 was considered statistically significant. Statistical analyses were performed using SPSS 12.0 (SPSS Inc., Chicago, IL, USA).
Results
Patient characteristics
The mean age of the HCC patients was 57.8±10.7 years, 83.3% (30/36) were male. The mean age of the controls was 47.4±11.1 years, with 57.1% (8/14) male. In the HCC group, 86.1% (31/36) of patients were HBV virus carriers vs. 7.2% (1/14) of controls. Nineteen HCC patients had at least one tumor nodule larger than 5cm. Tumors were well-differentiated in 13 patients, and moderately or poorly differentiated in 13 and 6 patients, respectively. Follow-up ranged from 2.2 to 79.5 months, with a median follow-up of 18.5 months. HCC recurred in 18 patients. The mean recurrence time was 6.0±5.9 months. Fourteen patients died during follow-up. The mean survival time was 10.4±7.1 months.
Serum alpha-fetoprotein (AFP) and serum GP73 levels
Twenty-one HCC patients had AFP > 20 μg/ml, among them 13 patients > 200 μg/ml. The median AFP level was 100.3 μg/ml with a range of 6.2-594.7μg/ml. All controls had AFP < 20 μg/ml, with a median value of 1.8 (0.9-4.8) μg/ml. The median sGP73 value in the HCC patients was 10.2 (4.8-18.4) relative units (RU), which was significantly elevated compared with controls (1.1 [0.7-1 1.4] RU, P<0.001) (Fig. 2A).
GP73 protein and mRNA expression in HCC, PL, and NL
The median protein level of GP73 in HCC tumors was 11.0 RU, with a range from 7.5-15.5 RU. This was significantly higher than that in PCL (3.9 [2.5-6.6] RU, P<0.001) and NL tissue (1.5 [1.1-2.4] RU, P<0.001) (Fig. 2C). Consistent with protein expressions, the mRNA level of GP73 in HCC tissue (3.3 [1.6-5.2] RU) was also significantly higher than that in PCL (1.8 [1.0-2.9] RU, P<0.01) and NL tissue (1.1 [0.7-1.4]) RU, P<0.001) (Fig. 2D).
Correlation between GP73 expression and clinicopathologic features
Serum GP73 levels in HCC patients with tumor size > 3cm did not differ significantly from that of the HCC patients with tumor size ≤ 3cm (9.0 [4.0-22.5] RU vs. 11.5 [5.9-16.1] RU, P=0.850) (Fig. 3A). However, tissue protein expressions of GP73 in HCC patients with tumor size > 3cm were markedly higher than those with tumor size ≤ 3cm (12.3 [9.3-16.5]) RU vs. 7.6 [5.0-12.4] RU, P<0.05) (Fig. 3A). GP73 protein levels in HCC patients with venous invasion were significantly increased when compared with patients without venous invasion (16.2 [11.2-21.5] RU vs. 9.9 [6.8-13.4] RU, P<0.05), whereas sGP73 levels did not differ significantly in HCC patients with or without venous invasion (6.4 [3.3-16.7] RU vs. 11.0 [6.2-20.1] RU, P=0.361) (Fig. 3B).
Overexpression of GP73 protein was seen in moderately differentiated tumors compared with well-differentiated (13.5 [10.0-18.5] RU vs. 9.7 [7.6-12.5] RU, P<0.05) and poorly differentiated ones (13.5 [10.0-18.5] RU vs. 5.4 [3.7-9.6] RU, P<0.05). We found no correlation between GP73 tissue protein overexpression and other clinicopathologic parameters, including patient age, gender, liver function, number of tumor nodules, AFP levels, and recurrence status (Table 1). GP73 mRNA expression in HCC patients had no statistical association with clinicopathologic parameters; neither did sGP73 levels (Table 1).
Relationship between GP73 levels and patient survival
We observed no statistically significant associations between survival time and GP73 expression.
Discussion
Data indicate that GP73 is a novel and promising serum biomarker for the early diagnosis of HCC.6,9,10,16,18-19 However, the mechanisms underlying the elevation of sGP73 and HCC tumorigenesis are unclear. To date, few clinical reports have been carried out on GP73 values in HCC tissues at both protein and mRNA levels, or on the correlations between its expression and clinicopathologic features.
In the present study, we investigated the values of GP73 in 36 paired HCC/PCL samples and 14 NL tissues by western blot and qRT-PCR instead of immunohistochemical methods to more accurately evaluate its expression pattern and potential clinicopathologic correlations. Our results showed that GP73 protein and mRNA were detected in all 36 of the HCC and PCL samples, and 14 NL tissues. Consistent with previous immunohistochemical studies, GP73 expression in HCC was significantly higher than that in the corresponding PCL and NL tissue at both protein and mRNA levels. The increased GP73 protein level was associated with tumor size, vein invasion, and tumor differentiation. These outcomes were contrary to those of corresponding sGP73 levels.
The regulation of GP73 and its function are controversial and have yet to be clarified.16, 20-21 The few studies on GP73 tissue expression pattern, mainly performed by immunohistochemistry, demonstrate that GP73 is expressed in epithelial cells of many human tissues, including biliary epithelial cells in normal liver, but not hepatocytes.14 However, the expression in hepatocytes can be upregulated in various liver diseases.14-15 The level of GP73 expression correlated with tumor grade by immunostatins in HCC.17 If PCL can be valued as cirrhotic liver tissue with potential to cancerization, it has yet to be determined how GP73 expression level in simple cirrhotic liver tissue without potential to cancerization compares with NL tissues. Further investigation may help clarify the role of GP73 in hepatocarcinogenesis.
We observed no significant correlation between the expression level of GP73 protein and mRNA in HCC samples. Genetic and epigenetic factors, such as DNA methylation, genetic mutation, and abnormal posttranscriptional regulations might have contributed to the difference. It is widely believed that AFP is mostly excreted by HCC. It is unknown whether elevated GP73 is also from tumor excretion, if it causes tumorigenesis in HCC, or is involved in cancer stem cells. From the limited data available, we hypothesize that the latter may be more likely. This could explain our finding that there was no significant positive correlation between GP73 protein level in HCC samples and sGP73 in the corresponding patients.
An important outcome of the current study was that the overexpression of GP73 at protein level is strongly associated with various clinicopathologic features, including tumor size, vein invasion, and tumor differentiation. These factors are highly correlated with invasion and metastasis of HCC.22,23 Our results indicate that tumors with larger load or stronger invasiveness may have a higher GP73 expression level, suggesting that the overexpression of GP73 protein might play a role in the advancement of HCC. We further stratified HCC patients by gender, age, liver function, number of tumor nodules, AFP levels, and recurrence status. Comparative analysis of GP73 protein expression showed no significant differences among the corresponding subgroups. It could be that these parameters do not interfere with GP73 expression, or that the difference is subtle.
We found no significant association between GP73 tissue expression and patient survival. Our previous large clinical trial indicated that the level of sGP73 had no correlation with tumor size and differentiation.6 Thus, the expression of sGP73 might not influence patient prognosis. To clarify this presumption, further well-designed clinical studies are needed.
In summary, this is the first demonstration of GP73 expression at both protein and mRNA levels, and investigation of its correlation with clinicopathologic features of HCC. The results show that GP73 expression is significantly elevated at both protein and mRNA levels. GP73 expression is correlated with tumor aggression, but whether it could be a prognostic marker requires further studies. Based on the presence of elevated GP73 protein in HCC, we propose that manipulation of GP73 expression in HCC patients might have therapeutic implications. Related reports, especially on GP73 functions and mechanisms of regulation in normal and HCC tissues, are limited. Further studies are warranted.
Potential conflict of interest: None.
Acknowledgment: This work was supported by the China Medical Board of New York (CMB, 06-837) and the National Natural Science Foundation of China (30788004).
References
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10 Marrero JA, Romano PR, Nikolaeva O, Steel L, Mehta A, Fimmel CJ, et al. GP73, a resident Golgi glycoprotein, is a novel serum marker for hepatocellular carcinoma. J Hepatol 2005; 43: 1007-1012.
11 Fimmel CJ, Wright L. Golgi protein 73 as a biomarker of hepatocellular cancer: development of a quantitative serum assay and expression studies in hepatic and extrahepatic malignancies. Hepatology 2009; 49: 1421-1423.
12 Gu Y, Chen W, Zhao Y, Chen L, Peng T. Quantitative analysis of elevated serum Golgi protein-73 expression in patients with liver diseases. Ann Clin Biochem 2009; 46: 38-43.
13 Bachert C, Fimmel C, Linstedt AD. Endosomal trafficking and proprotein convertase cleavage of cis Golgi protein GP73 produces marker for hepatocellular carcinoma. Traffic 2007; 8: 1415-1423.
14 Kladney RD, Bulla GA, Guo L, Mason AL, Tollefson AE, Simon DJ, et al. GP73, a novel Golgi-localized protein upregulated by viral infection. Gene 2000; 249: 53-65.
15 Kladney RD, Cui X, Bulla GA, Brunt EM, Fimmel CJ. Expression of GP73, a resident Golgi membrane protein, in viral and nonviral liver disease. Hepatology 2002; 35: 1431-1440.
16 Iftikhar R, Kladney RD, Havlioglu N, Schmitt-Gräff A, Gusmirovic I, Solomon H, et al. Disease- and Cell-Specific Expression of GP73 in Human Liver Disease. Am J of Gastroenterol 2004; 99:1087-1095.
17 Riener MO, Stenner F, Liewen H, Soll C, Breitenstein S, Pestalozzi BC, et al. Golgi phosphoprotein 2 (GOLPH2) expression in liver tumors and its value as a serum marker in hepatocellular carcinomas. Hepatology 2009; 49: 1602-1609.
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Figure legends
Figure 1 Portal venous invasion in histopathologic examination: HE staining, 40×.
Figure 2 sGP73 significantly increased in HCC patients and GP73 is over-expressed at protein and mRNA level in HCC tissues.
(A) sGP73 in HCC patients (10.2 [4.8-18.4] RU) was significantly higher than in hepatic hemangioma patients (1.1 [0.7-1.4] RU, P<0.001).
(B) Tissues of HCC, PCL, and NL were extracted for western blot analysis: 1 and 4 are protein extractions of NL tissues from 2 patients with hepatic hemangioma; 2 and 5 are PCL tissues from 2 patients with HCC; 3 and 6 are the corresponding HCC tissues from the 2 HCC patients. GAPDH was used as a loading control to confirm the equality of total added tissue protein.
(C) At protein expression level, GP73 level in HCCs (11.0 [7.5-15.5] RU) was significantly higher than in PCLs (3.9 [2.5-6.6] RU, P<0.001) and NLs (1.5 [1.1-2.4] RU, P<0.001)
(D) At mRNA expression level, GP73 level in HCCs (3.3 [1.6-5.2] RU) was significantly higher than in PCLs (1.8 [1.0-2.9] RU, P<0.01) and NLs (1.1 [0.7-1.4] RU, P<0.001).
Figure 3 GP73 is overexpressed at the protein level in HCC with tumor size > 3cm and tumors with vein invasion
(A) GP73 expression at protein level in HCC with tumor size > 3cm was significantly higher than in tumor size ≤3 cm (12.3 [9.3-16.5] RU vs. 7.6 [5.0-12.4] RU, P<0.05). The sGP73 difference between the corresponding subgroups of patients was not significant: (8.96 [4.03-22.50] RU vs. 11.54 [5.87-16.06] RU, P=0.850).
(B) GP73 expression at protein level in HCC patients with vein invasion had a significantly higher GP73 level than in HCC patients without vein invasion (16.2 [11.2-21.5] RU vs. 9.9 [6.8-13.4] RU, P<0.05). sGP73 in HCC patients with vein invasion was similar to that in patients without vein invasion (6.4 [3.3-16.7] RU vs. 11.0 [6.2-20.1] RU, P=0.361)
Table 1. Relationships between GP73 expression on protein and mRNA levels, sGP73 and clinicopathological features in 36 cases of HHC
Clinicopathological features |
N |
GP73 expression | ||
mRNA |
Protein |
sGP73 | ||
Age(y) |
|
|
|
|
≥50 |
29 |
3.13(1.45-5.18) |
10.80(7.10-13.80) |
9.78(4.82-18.55) |
<50 |
7 |
3.71(1.58-6.84) |
12.40(7.40-20.60) |
16.03(4.70-18.73) |
Sex |
|
|
|
|
Male |
30 |
3.07(1.49-4.88) |
11.50(7.35-16.10) |
10.64(4.31-19.31) |
Female |
6 |
5.98(4.02-8.05) |
9.25(7.05-13.43) |
9.37(8.61-18.95) |
Child Classification |
|
|
|
|
A |
31 |
3.13(1.23-5.17) |
11.90(7.40-16.20) |
10.55(4.58-18.73) |
B |
5 |
4.99(2.97-7.27) |
7.60(7.10-12.40) |
8.96(5.86-19.49) |
HBV |
|
|
|
|
(+) |
31 |
3.34(1.68-5.17) |
10.00(7.40-14.00) |
11.54(4.58-21.03) |
(-) |
5 |
3.13(0.67-16.42) |
12.50(7.90-30.15) |
8.00(5.29-9.38) |
Tumor Grade |
|
|
|
|
W |
13 |
3.34(1.40-5.05) |
9.70(7.60-12.45) |
8.96(6.95-16.05) |
M |
17 |
3.13(2.00-5.64) |
13.50(10.00-18.50) † |
10.55(4.64-29.00) |
P |
6 |
3.76(0.49-8.05) |
5.35(3.65-9.60) |
12.42(2.87-18.95) |
Tumor Size(cm) |
|
|
|
|
>3 |
25 |
3.13(1.71-5.99) |
12.30(9.25-16.45) |
8.96(4.03-22.50) |
≤3 |
11 |
3.34(1.12-4.78) |
7.60(5.00-12.40) § |
11.54(5.87-16.06) |
Tumor Nodule |
|
|
|
|
Solitary |
23 |
3.68(1.58-5.19) |
11.90(7.60-16.20) |
14.10(5.06-23.96) |
Multiple |
13 |
3.00(1.62-5.18) |
10.00(6.30-15.00) |
9.78(4.64-13.30) |
Vein Invasion |
|
|
|
|
Positive |
8 |
3.17(1.47-6.06) |
16.25(11.20-21.50) |
6.35(3.27-16.73) |
Negative |
28 |
3.41(1.60-5.19) |
9.90(6.80-13.38) δ |
11.05(6.16-20.09) |
AFP (IU/ml) |
|
|
|
|
>1000 |
7 |
3.13(2.27-6.84) |
14.00(10.80-16.20) |
8.00(4.70-23.96) |
<1000 |
29 |
3.34(1.40-5.14) |
10.00(6.70-13.55) |
10.55(4.82-16.67) |
Recurrence Status |
|
|
|
|
Yes |
18 |
3.17(1.57-5.43) |
12.10(9.13-14.50) |
7.51(3.41-15.61) |
No |
18 |
3.41(1.49-5.57) |
9.40(5.75-16.25) |
14.48(8.05-25.20) |
W, well differentiated; M, moderately differentiated; P, poorly differentiated.
† On protein expression level, moderately differentiated tumors had a significantly higher GP73 level than well differentiated tumors (13.5 [10.0-18.5] RU vs. 9.7 [7.6-12.5] RU, P<0.05); But in poorly differentiated tumors, GP73 levels were significantly lower than in moderately differentiated ones (5.4 [3.7-9.6] RU vs. 13.5 [10.0-18.5] RU, P<0.05). They were also significantly lower than in well differentiated tumors (5.4 [3.7-9.6] RU vs. 9.7 [7.6-12.5] RU, P<0.05).
§ GP73 levels in tumors from HCC patients with tumor size >3cm were significantly higher than those from HCC patients with tumor size ≤3cm (12.3 [9.3-16.5] RU vs. 7.6 [5.0-12.4] RU, P<0.05).
δ GP73 level in tumors with vein invasion were significantly higher than those without vein invasion (16.2 [11.2-21.5] RU vs. 9.9 [6.8-13.4] RU, P<0.05).
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