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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 34  |  Issue : 2  |  Page : 564-569

Study of Golgi protein 73 in patients with hepatitis C virus-related hepatocellular carcinoma


1 Department of Internal Medicine, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Pathology, Faculty of Medicine, Menoufia University, Menoufia, Egypt

Date of Submission05-Sep-2019
Date of Decision07-Oct-2019
Date of Acceptance12-Oct-2019
Date of Web Publication30-Jun-2021

Correspondence Address:
Amr S Ibrahim
Quesna, Menoufia
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_275_19

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  Abstract 


Objective
The aim of the present work is to investigate the expression of Golgi protein 73 (GP73) in serum in patients with hepatocellular carcinoma (HCC) and determine its efficacy as a screening test in early detection of HCC.
Background
Serum GP73 is a promising biomarker for detection of HCC.
Patients and methods
This case–control study involved 30 patients with HCC, 30 patients with liver cirrhosis, and 15 healthy controls. Clinical examination, abdominal ultrasonography, and triphasic computed tomography for focal lesion were performed. Liver function tests were performed using clinical autoanalyzer, serum α-fetoprotein (AFP) was measured using enzyme-linked immune-sorbent assay method, and GP73 was determined by enzyme-linked immune-sorbent assay kit for GP73. Data were collected and statistically analyzed.
Results
GP73 was highly significantly higher in HCC group than cirrhotic and control groups. The sensitivity of GP73 in diagnosis of HCC was 83% and the specificity was 74%, at a cutoff point of 111 ng/ml, elicited from the receiver operator characteristic curve, with very good area under curve of 0.909, whereas that the sensitivity of AFP was 36.7% and the specificity was 100% at a cutoff point of 400 ng/ml, elicited from the receiver operator characteristic curve, with very good area under curve of 0.903.
Conclusion
GP73 is highly associated with HCC and is more sensitive than AFP for early detection of HCC.

Keywords: α-fetoprotein, enzyme-linked immune-sorbent assay, Golgi protein 73, hepatocellular carcinoma


How to cite this article:
Dala AG, Ezz EAA, Sonbol AA, Ibrahim AS. Study of Golgi protein 73 in patients with hepatitis C virus-related hepatocellular carcinoma. Menoufia Med J 2021;34:564-9

How to cite this URL:
Dala AG, Ezz EAA, Sonbol AA, Ibrahim AS. Study of Golgi protein 73 in patients with hepatitis C virus-related hepatocellular carcinoma. Menoufia Med J [serial online] 2021 [cited 2024 Mar 29];34:564-9. Available from: http://www.mmj.eg.net/text.asp?2021/34/2/564/319679




  Introduction Top


Liver cancer is the fifth most common cancer and the second most frequent cause of cancer-related death globally [1]. Approximately, 80–90% of hepatocellular carcinoma (HCC) cases occur in the setting of underlying cirrhosis; thus, any etiological agent leading to cirrhosis should be considered as a risk factor for HCC [2]. The current guidelines recommend surveillance for individuals with cirrhosis using liver US with/or without α-fetoprotein (AFP) every 6 months [3]. The lack of effective screening tests necessitates investigation for new HCC markers [4]. Golgi protein 73 (GP73) is a 73-kDa type II Golgi membrane protein expressed mostly in epithelial cells of many human tissues. In normal livers, GP73 is consistently present in biliary epithelial cells. Nevertheless, the expression of GP73 was notably increased in numerous liver diseases, especially in HCC cells [5]. GP73 is reported to be a novel tumor marker for HCC. The collective conclusion from many studies is that the sensitivity and specificity of serum GP73 levels as a diagnostic marker are superior to those of AFP for HCC [6],[7]. The aim of this study is to investigate the expression of GP73 in serum in patients with HCC and determine its efficacy as a screening test in early detection of HCC.


  Patients and methods Top


This case–control study consisted of 75 participants who visited the Oncology and Internal Medicine Department at Menoufia Liver Institute during the period from June 2018 till December 2018.

Participants were classified into three groups: group I included 30 patients with HCC, group II included 30 patients with liver cirrhosis, and group III included 15 healthy participants as a control group.

Inclusion criteria included patients with hepatitis C virus-related liver cirrhosis and HCC, whereas patients with other malignancies or HCC distant metastasis were excluded.

Medical history taking and complete physical examination with particular emphasis on signs of chronic liver disease were done for all participants.

Laboratory data included complete blood picture analyzed in an automated ADVIA-120 hematological analyzer; renal function tests (blood urea and serum creatinine) analyzed in Integra 400 Autoanalyzer; integra Oststeinbek, Germany; data on liver function tests [aspartate transaminase (AST), alanine transaminase (ALT), serum bilirubin, and serum albumin] analyzed in AU480 analyzer; Beckman California, USA; serum AFP measured using enzyme-linked immune-sorbent assay (ELISA) method; and GP73 determined by ELISA kit provided by SunRed Biotechnology Company (Shanghai, China), according to the recommendation of the manufacturer. The kit uses a double-antibody sandwich ELISA to assay the level of GP73 samples. Data were collected and statistically analyzed.

Radiological investigations were done like ultrasound and triphasic computerized tomography on the abdomen and pelvis.

Clinical and laboratory data of the cases were tabulated.

All participants participated in the study voluntarily, and written informed consent was obtained from each participant. The study complied with the Faculty of Medicine, Menoufia University.

Data entry, coding, and analysis were conducted using SPSS (22), IBM Corp, Released 2013 (IBM SPSS Statistics for Windows, Version 22.0;IBM Corp., Armonk, New York, USA). Description of quantitative variables was in the form of mean ± SD, and description of qualitative variables was by frequency and percentage. χ2-Test was used to assess the relationship between two qualitative groups, and t-test was used to assess the relationship between two quantitative groups. P value less than or equal to 0.05 was set to be statistically significant and P value less than or equal to 0.001 was set to be highly significant.


  Results Top


Regarding age, the mean age was 62 ± 6.9 years in HCC group, 58.6 ± 4.5 years in cirrhotic group, and 35.5 ± 8.9 years in control group. So, there was no significant difference between HCC and cirrhotic groups (P1 = 0.06), but the mean age in HCC group was highly significantly higher than control group (P2 = 0.001), and the mean age in cirrhotic group was highly significantly higher than control group (P3 = 0.001). Regarding sex, in HCC group, there were 25 (83.3%) males and five (16.7%) females; in cirrhotic group, there were 17 (56.7%) males and 13 (43.3%) females; and in control group, there were 11 (73.3%) males and four (26.7%) females. So, there was no significant difference between the studied groups regarding sex (P = 0.07) [Table 1].
Table 1: Statically comparison among studied groups regarding age and sex

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Regarding laboratory tests, the mean white blood cell count was 5.38 ± 2.46 × 103/mm2, 6.67 ± 3.25 × 103/mm2 and 7.02 ± 1.6 × 103/mm2 for HCC, cirrhotic, and control groups, respectively. So, there was no significant difference between the studied groups regarding white blood cell count (P = 0.086). Regarding platelets, the mean platelet count was 114.36 ± 41.9 × 103/mm2, 93.6 ± 30.6 × 103/mm2, and 243.8 ± 96.9 × 103/mm2 for HCC, cirrhotic, and control groups, respectively. So, there was no significant difference between HCC and cirrhotic groups regarding platelet count (P1 = 0.08), but the mean platelet count in HCC group was highly significantly lower than control group (P2 = 0.001), and the mean platelet count was highly significantly lower in cirrhotic group than control group (P3 = 0.001). Regarding hemoglobin level, the mean hemoglobin level was 11.61 ± 1.75, 10.12 ± 1.5, and 12.2 ± 0.67 g/dl for HCC, cirrhotic, and control groups, respectively. So, the mean hemoglobin level in cirrhotic group was significantly lower than HCC group (P1 = 0.003). There was no significant difference between HCC and control groups regarding mean hemoglobin level (P2 = 0.2), and the mean hemoglobin level in cirrhotic group was highly significant lower than control group (P3 = 0.001). Regarding ALT, the mean ALT level was 44.42 ± 16.3, 55.5 ± 25.8, and 20.4 ± 3.2 μl/l for HCC, cirrhotic, and control groups, respectively. So, there was no significant difference between HCC and cirrhotic groups regarding mean ALT level (P1 = 0.12), but the mean ALT level in HCC group was highly significant higher than control group (P2 = 0.001), and the mean ALT level in cirrhotic group was highly significant higher than control group (P3 = 0.001). Regarding AST, the mean AST level was 49.35 ± 19.29, 71.5 ± 16.17, and 23.06 ± 3.8 μl/l for HCC, cirrhotic, and control groups, respectively. So, there was no significant difference between HCC and cirrhotic groups regarding mean AST level (P1 = 0.15), but the mean AST level in HCC group was highly significantly higher than control group (P2 = 0.001), and the mean AST level in cirrhotic group was highly significantly higher than control group (P3 = 0.001). Regarding albumin, the mean albumin level was 3.32 ± 0.45, 2.88 ± 0.34, and 4.03 ± 0.13 g/dl for HCC, cirrhotic, and control groups, respectively. So, the mean albumin level in HCC group was highly significant higher than cirrhotic group (P1 = 0.001), the mean albumin level in HCC group was highly significant lower than control group (P2 = 0.001), and the mean albumin level in cirrhotic group was highly significantly lower than control group (P3 = 0.001). Regarding total bilirubin, the mean total bilirubin level was 1.32 ± 0.77, 1.6 ± 0.48, and 0.93 ± 0.18 mg/dl for HCC, cirrhotic, and control groups, respectively. So, there was no significant difference between HCC and cirrhotic groups regarding mean total bilirubin level (P1 = 0.2), but the mean total bilirubin level in HCC group was significantly higher than control group (P2 = 0.03), and the mean total bilirubin level in cirrhotic group was highly significant higher than control group (P3 = 0.001). Regarding direct bilirubin, the mean direct bilirubin level was 0.66 ± 0.51, 0.58 ± 0.3, and 0.18 ± 0.04 mg/dl for HCC, cirrhotic, and control groups, respectively. So, there was no significant difference between HCC and cirrhotic groups regarding mean direct bilirubin level (P1 = 0.7), but the mean direct bilirubin level in HCC group was highly significantly higher than control group (P2 = 0.001), and the mean direct bilirubin level in cirrhotic group was highly significant higher than control group (P3 = 0.001). Regarding international normalized ratio (INR), the mean INR value was 1.23 ± 0.15, 1.4 ± 0.32, and 1.08 ± 0.08 for HCC, cirrhotic, and control groups, respectively. So, the mean INR value in HCC group was significant lower than cirrhotic group (P1 = 0.02), the mean INR value in HCC group was highly significant higher than control group (P2 = 0.001), and the mean INR value in cirrhotic group was highly significant higher than control group (P3 = 0.001) [Table 2].
Table 2: Statically comparison among studied groups regarding laboratory tests

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Regarding AFP, the mean AFP level was 383.48 ± 607, 5.8 ± 4.1, and 1.9 ± 0.73 ng/ml in HCC, cirrhotic, and control groups, respectively. So, the mean AFP level in HCC group was significantly higher than cirrhotic group (P1 = 0.005), the mean AFP level in HCC group was highly significantly higher than control group (P2 = 0.001), and the mean AFP level in cirrhotic group was highly significantly higher than control group (P3 = 0.001). Regarding GP73, the mean GP73 level was 201 ± 81.7, 93.6 ± 26.6, and 19.4 ± 0.4 ng/ml in HCC, cirrhotic, and control groups, respectively. So, the mean GP73 level in HCC group was highly significantly higher than cirrhotic group (P1 = 0.001), the mean GP73 level in HCC group was highly significantly higher than control group (P2 = 0.001), and the mean GP73 level in cirrhotic group was highly significantly higher than control group (P3 = 0.001) [Table 3].
Table 3: Statistical comparison among studied groups regarding α-fetoprotein and Golgi protein 73 tests

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For AFP, sensitivity and specificity were 36.7 and 100%, respectively, with 100% positive predictive value and 61.2% negative predictive value at a cutoff point of 400 ng/ml with very good area under the curve (AUC) of 0.903. For GP73, sensitivity and specificity were 83 and 74%, respectively, with 75.8% positive predictive value and 81.5% negative predictive value at a cutoff point of 111 ng/ml, with very good AUC of 0.909. For combination of two tests, sensitivity and specificity were 83 and 74%, respectively, with 75.8% positive predictive value and 81.5% negative predictive value at a cutoff point of 400 ng/dl for AFP and 111 ng/ml for GP73 with good AUC of 0.783 [Table 4].
Table 4: Sensitivity and specificity of α-fetoprotein and Golgi protein 73 for screening of hepatocellular carcinoma

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  Discussion Top


In the current study, the mean age was highly significant higher in HCC (62 ± 6.9 years) and liver cirrhosis (58.6 ± 4.5 years) groups than in the control group (35.5 ± 8.9 years), and no significant difference between group of HCC (62 ± 6.9 years) and group of liver cirrhosis (58.6 ± 4.5 years). Our results are close to Paranaguá-Vezozzo et al. [8], who reported that the mean age was 59 years old in HCC and cirrhotic group with no significant difference. In contrast to our results, Baghdady et al. [9] reported that the mean age was highly significantly higher in HCC group (58.7 ± 5.76) than in non-HCC group (46.72 ± 9). Our results showed that HCC was highly prevalent in males. Group of HCC included 25 (83.3%) males and five (16.7%) females, with male to female ratio of 5:1, whereas in cirrhotic group, 17 (56.7%) were males and 13 (43.3%) were females. Our results agreed with Liu et al. [10], who reported an overall male-to-female ratio in age-standardized rate of 3.55. The sex ratio was below 2 at ages less than 25 years, increased with age from 25 to 29 years until peaking at 5.40 at ages 50–54 years, and declined thereafter.

Our study showed regarding platelet count that there was a highly significant difference between HCC group and control group and between cirrhotic group and control group, being lower platelet count in HCC and cirrhotic groups, with no significant difference between HCC and cirrhotic groups, and regarding hemoglobin concentration, it showed significant difference between HCC and cirrhotic groups and highly significant difference between cirrhotic group and control group, being lower hemoglobin concentration in cirrhotic group. Our results were in agreement with Omar et al. [11], who showed that the mean hemoglobin concentration was highly significantly lower in cirrhotic group than HCC group (P = 0.001) and showed no significant difference regarding the mean platelet count between HCC group and cirrhotic group. In contrary to our results, Paranaguá-Vezozzo et al. [8] showed that the mean platelet count was significant lower in HCC group than cirrhotic group (P = 0.02).

Our study showed that the mean ALT and AST values were highly significant higher in HCC group and cirrhotic group than in control group (P = 0.001), with no significant difference between HCC group and cirrhotic group. Our study showed that there was a highly significant difference regarding mean values of serum albumin, total and direct bilirubin, and INR between HCC group and control group and between cirrhotic group and control group, being lower albumin and higher total and direct bilirubin and INR in HCC group and cirrhotic group, whereas the study showed significant difference regarding serum albumin and INR between HCC and cirrhotic groups, being lower albumin and higher INR in cirrhotic group, with no significant difference between HCC and cirrhotic groups regarding total and direct bilirubin. Our results agreed with Omar et al. [11], who showed that both ALT and AST mean values were highly significant higher in HCC group and cirrhotic group than in control group (P = 0.001), whereas there was no significant difference between HCC group and cirrhotic group (P = 0.05). Moreover, they reported that serum albumin, total bilirubin. and INR showed highly significant difference between HCC group and control group, and between cirrhotic group and control group, being lower serum albumin, higher serum bilirubin, and higher INR level in HCC and cirrhotic groups (P = 0.001). Our results were in contrary to Paranaguá-Vezozzo et al. [8], who showed that both ALT and AST mean values were significantly higher in HCC group than in cirrhotic group (P = 0.002).

AFP has served as a diagnostic test for HCC since the 1970s, owing to there being a correlation between elevated levels of AFP and the occurrence of HCC. However, AFP as a sole indicator of HCC is of limited value as reported by Jia et al. [12].

Our study showed that the mean AFP level in HCC group was significant higher than cirrhotic group, whereas the mean AFP level in HCC group was highly significant higher than control group, and the mean AFP level in cirrhotic group was highly significant higher than control group. Our results agreed with Omar et al. [11], who reported that serum AFP is highly significant higher in HCC group than cirrhotic and control groups.

Our study showed that the mean GP73 level in HCC group was highly significant higher than cirrhotic and control groups, and the mean GP73 level in cirrhotic group was highly significant higher than control group. Our results agreed with Jiao et al. [13], who reported that the difference of GP73 among the all groups has a statistical significance. Moreover, our results were close to Fouad et al. [7], who showed that serum GP73 levels were significantly higher in patients with HCC compared with those with chronic liver disease.

Our study showed that the sensitivity of AFP in diagnosis of HCC was 36.7% and the specificity was 100%, at a cutoff level of 400 ng/ml), elicited from the receiver operator characteristic (ROC) curve, with very good AUC of 0.903. Our results were close to Jia et al. [12], who reported that of the 102 samples from patients with HCC, 53 (51.96%) samples were positive for AFP at a cutoff point of 400 ng/ml. Most authors have found that an isolated measurement of serum AFP levels had limited success for early HCC screening, but even small changes in AFP levels may be a predictor for HCC as reported by El-Serag et al. [14] In fact, dynamic AFP measurement could identify patients at higher risk of HCC occurrence, as recently shown by Bird et al. [15].

Our study showed that the sensitivity of GP73 for diagnosis of HCC was 83% and the specificity was 74% at a cutoff point of 111 ng/ml, elicited from the ROC curve, with very good AUC of 0.909. Our results were close to Jiao et al. [13], who reported that when ROC curves were plotted to define the optimal cutoff values and to identify the sensitivity and specificity for serum GP73 and AFP in differentiating patients with HCC versus those with hepatitis, the area under the ROC (AUROC) curve for GP73 was 0.840, with a sensitivity of 78.3%, specificity of 85.4%, and an optimal cutoff point of 117.53 ng/ml. Our study showed that the sensitivity of GP73 combined with AFP in diagnosis of HCC was 83% and the specificity was 74% at a cutoff point of 111 ng/ml for GP73 and 400 ng/ml for AFP, elicited from the ROC curve, with a good AUROC of 0.783. Our results were close to Jia et al. [12], who reported that the determination of GP73 in combination with AFP increases the sensitivity and specificity in diagnosis of HCC, especially in individuals with total AFP less than 400 ng/ml. Thus, GP73 should be a useful biomarker, in combination with AFP, to confirm the diagnosis of HCC.


  Conclusion Top


We concluded that GP73 is a valuable serum marker that can aid the early diagnosis of HCC. In combination, measurements of AFP and GP73 have the advantage to improve the detection of one of the most common malignancies worldwide.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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