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  Table of Contents  
ORIGINAL ARTICLE
Year : 2015  |  Volume : 52  |  Issue : 6  |  Page : 105-106
 

Predictive value of recurrence for serum hypoxia inducible factor-1α C-reaction protein in hepatocellular carcinoma patients after transcatheter arterial chemoembolization


Tianjin Hepatopathy Research Institute, Tianjin Second People's Hospital, Tianjin 300192, PR, China

Date of Web Publication24-Dec-2015

Correspondence Address:
L Wei
Tianjin Hepatopathy Research Institute, Tianjin Second People's Hospital, Tianjin 300192
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.172504

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 » Abstract 

Objectives: The purpose of this study was to evaluate the predictive value of recurrence for serum hypoxia inducible factor-1α (HIF-1α), C-reaction protein (CRP) in hepatocellular carcinoma patients after transcatheter arterial chemoembolization (TACE). Patients and Methods: Fifty-eight hepatocellular carcinoma patients treated with TACE were included in this study from February 2010 to January 2013 as the case group. Of the included 58 cases, 47 patients had recurrence disease, and other 11 cases had no recurrence disease within 2 years follow-up. Moreover, 62 subjects with no benign liver disease were recruited as a control group in the same period. The serum level of HIF-1α and CRP were tested in case group and control group 1-week after TACE. The serum level of HIF-1α and CRP were compared among the recurrence, nonrecurrence, and benign liver disease patients. The predictive value of recurrence for serum HIF-1α, CRP was calculated by Bayes' theorem. Results: The serum HIF-1α and CRP level was arrayed 1-week after TACE. For recurrence cases, the serum level of HIF-1α and CRP was 2457.00 ± 335.70 pg/ml and 11.46 ± 3.25 mg/L. For nonrecurrence subjects, the serum level of HIF-1α and CRP was 2067.00 ± 175.900 pg/ml and 8.99 ± 1.70 mg/L. Moreover, for the benign liver disease patients, the serum level of HIF-1α and CRP was 1897.00 ± 121.33 pg/ml and 6.11 ± 1.2 mg/L. The serum level of HIF-1α and CRP was significantly higher in hepatocellular carcinoma patients than that of benign liver disease patients (P < 0.05); The recurrence predictive sensitivity and specificity of HIF-1α for hepatocellular carcinoma patients after TACE chemoembolization was 76.60% and 81.82% with the area under the curve (AUC) receiver operating characteristic (ROC) curve of 0.85; The recurrence predictive sensitivity and specificity of CRP for hepatocellular carcinoma patients after TACE was 65.96% and 63.64% with the AUC/ROC of 0.74. Conclusion: The serum level of HIF-1α and CRP was elevated in recurrence patients which could be a potential marker for recurrence prediction.


Keywords: C-reaction protein, hepatocellular carcinoma, hypoxia inducible factor-1α, predictive value, transcatheter arterial chemoembolization


How to cite this article:
Jing Q, Jianyong L, Jiming Y, Shuren L, Rui W, Wei L. Predictive value of recurrence for serum hypoxia inducible factor-1α C-reaction protein in hepatocellular carcinoma patients after transcatheter arterial chemoembolization. Indian J Cancer 2015;52, Suppl S2:105-6

How to cite this URL:
Jing Q, Jianyong L, Jiming Y, Shuren L, Rui W, Wei L. Predictive value of recurrence for serum hypoxia inducible factor-1α C-reaction protein in hepatocellular carcinoma patients after transcatheter arterial chemoembolization. Indian J Cancer [serial online] 2015 [cited 2019 Sep 19];52, Suppl S2:105-6. Available from: http://www.indianjcancer.com/text.asp?2015/52/6/105/172504

Jing Q and Jianyong L contributed equally to this work



 » Introduction Top


Hepatocellular carcinoma is one of the most diagnosed malignant carcinoma of the digestive system with high mortality rate and recurrence rate.[1],[2] For the hepatocellular carcinoma patients with early stage, resection is recommended according to the guideline. However, most of the patients with hepatocellular carcinoma had advanced stage disease when diagnosis.[3] Moreover, the operation is not suitable for these advanced or metastasis patients.[4] The patients with advanced or metastasis disease should receive comprehensive treatment such as chemotherapy or radiotherapy. Transcatheter arterial chemoembolization (TACE) is reported to be an important method for treatment of advanced or metastasis stage hepatocellular carcinoma.[5],[6] However, recurrence rate in patients treated with TACE was relatively high. Thus in this study, we recruited 58 cases treated with TACE to discuss the predictive value of recurrence for serum hypoxia inducible factor-1α (HIF-1α), C-reaction protein (CRP) in hepatocellular carcinoma patients after TACE.


 » Patients and Methods Top


Fifty-eight hepatocellular carcinoma patients treated with TACE were included in this study from February 2010 to January 2013 as the case group in The 2nd People's Hospital of Tianjin. Of the included 58 cases, 47 patients had recurrence disease, and other 11 cases had no recurrence disease within 2 years follow-up. Moreover, 62 subjects with no benign liver disease were recruited as a control group in the same period. The mean age was 52.1 ± 12.2 with 46 male and 12 female patients in the hepatocellular carcinoma group. Moreover, the mean age was 54.6 ± 10.5 with 43 male and 19 female patients in the benign liver group. No statistical difference in mean age and gender was found between the two groups. The serum level of HIF-1α and CRP was tested in case group and control group 1-week after TACE. The serum level of HIF-1α and CRP was compared among the recurrence, nonrecurrence, and benign liver disease patients. The predictive value of recurrence for serum HIF-1α, CRP was calculated by Bayes' theorem.

Statistical analysis

Frequencies were expressed as numbers and percentages. The Chi-square test was used for countable data. Student's t-test was used to compare means and P < 0.05 was considered statistically significant. The Bayes' theorem was used to calculated the diagnosis sensitivity and specificity. All the data analysis was done by Stata11.0 software (http://www.stata.com; Stata Corporation, College Station, TX, USA).


 » Results Top


Serum hypoxia inducible factor-1α C-reaction protein

The serum HIF-1α and CRP level was arrayed 1-week after TACE. For recurrence cases, the serum level of HIF-1α and CRP was 2457.00 ± 335.70 pg/ml and 11.46 ± 3.25 mg/L. For nonrecurrence subjects, the serum level of HIF-1α and CRP was 2067.00 ± 175.90 pg/ml and 8.99 ± 1.70 mg/L. Moreover, for the benign liver disease patients, the serum level of HIF-1α and CRP was 1897.00 ± 121.33 pg/ml and 6.11 ± 1.26 mg/L [Table 1]. The serum level of HIF-1α and CRP was significantly higher in hepatocellular carcinoma patients than that of benign liver disease patients (P < 0.05).
Table 1: The serum level of HIF- 1μ CRP (x̄±s)

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The predictive value of recurrence

The recurrence predictive sensitivity and specificity of HIF-1α for hepatocellular carcinoma patients after TACE was 76.60% and 81.82% with the area under the curve (AUC) receiver operating characteristic (ROC) curve of 0.85; the recurrence predictive sensitivity and specificity of CRP for hepatocellular carcinoma patients after TACE was 65.96% and 63.64% with the AUC/ROC curve of 0.74 [Figure 1].
Figure 1: The recurrence predictive area under the curve receiver operating characteristic for hypoxia inducible factor-1α C-reaction protein

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 » Discussion Top


Hepatocellular carcinoma is an important cause of cancer-related death world, especially in China with high mortality and recurrence rate.[7] Because of difficulty diagnosis in early stage, patients with hepatocellular carcinoma were usually had advanced or metastasis stage disease. Moreover, the operation is not suitable for these patients. For the advanced stage patients, TACE was widely applied. TACE has been shown to increase survival in patients with advanced stages.[8] However, the recurrence rate was relatively high in patients treated with TACE. It was reported that about 80% patients received TACE treatment had recurrence disease in the following 2 years.[9] The prognosis of patients with recurrence disease was poor. Hence, it is important to find the risk factors for recurrence of patients received TACE treatment.[10] The general methods for detection recurrence disease were computed tomography or type-B ultrasonography with high sensitivity and specificity. However, these methods cannot predict the recurrence risk for hepatocellular carcinoma who received TACE. Moreover, recent study indicated that the serum level of HIF-1α and CRP was elevated in recurrence hepatocellular carcinoma patients which indicated that the serum HIF-1α and CRP could be a potential biomarker for recurrence.

HIFs are transcription factors that respond to changes in available oxygen in the cellular environment. The HIF signaling cascade mediates the effects of hypoxia, the state of low oxygen concentration, on the cell. Hypoxia often keeps cells from differentiating. However, hypoxia promotes the formation of blood vessels, and is important for the formation of a vascular system in embryos, and cancer tumors.[11],[12] Hence, the high expression of HIF was associated with high-risk of developing recurrence. In our study, we found that the serum level of HIF-1α in the recurrence group was higher than the nonrecurrence group 1-week after the TACE, which indicated that the serum HIF-1α could be a potential biomarker. Moreover, further analysis indicated the recurrence predictive sensitivity and specificity were 76.60% and 81.82% with the ROC/AUC curve of 0.85. The results indicated that the serum HIF-1α had a relative high predictive value of recurrence for hepatocellular carcinoma patients. Moreover, the serum CRP was also significantly elevated in recurrence group with the diagnosis recurrence sensitivity and specificity of 65.96% and 63.64% with the AUC/ROC curve of 0.74.


 » Conclusion Top


The serum level of HIF-1α and CRP was significantly elevated 1-week after TACE in recurrence patients which could be a potential marker for recurrence prediction.

 
 » References Top

1.
Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin 2012;62:10-29.  Back to cited text no. 1
    
2.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011;61:69-90.  Back to cited text no. 2
    
3.
Attwa MH, El-Etreby SA. Guide for diagnosis and treatment of hepatocellular carcinoma. World J Hepatol 2015;7:1632-51.  Back to cited text no. 3
    
4.
Chen KW, Ou TM, Hsu CW, Horng CT, Lee CC, Tsai YY, et al. Current systemic treatment of hepatocellular carcinoma: A review of the literature. World J Hepatol 2015;7:1412-20.  Back to cited text no. 4
    
5.
Murata S, Mine T, Ueda T, Nakazawa K, Onozawa S, Yasui D, et al. Transcatheter arterial chemoembolization based on hepatic hemodynamics for hepatocellular carcinoma. ScientificWorldJournal 2013;2013:479805.  Back to cited text no. 5
    
6.
Colombo M, Sangiovanni A. Treatment of hepatocellular carcinoma: Beyond international guidelines. Liver Int 2015;35 Suppl 1:129-38.  Back to cited text no. 6
    
7.
McGlynn KA, Petrick JL, London WT. Global epidemiology of hepatocellular carcinoma: An emphasis on demographic and regional variability. Clin Liver Dis 2015;19:223-38.  Back to cited text no. 7
    
8.
Liapi E, Geschwind JF. Combination of local transcatheter arterial chemoembolization and systemic anti-angiogenic therapy for unresectable hepatocellular carcinoma. Liver Cancer 2012;1:201-15.  Back to cited text no. 8
    
9.
Jian L, Lisong T. The effect of serum VEGF and C-protein expression in predicting the recurrence of elderly patients with liver cancer. Chin J Gerontol 2014;6:106-7.  Back to cited text no. 9
    
10.
Jeong SW, Jang JY, Lee JE, Lee SH, Kim SG, Cha SW, et al. The efficacy of hepatic arterial infusion chemotherapy as an alternative to sorafenib in advanced hepatocellular carcinoma. Asia-Pacific Journal of Clinical Oncology 2012;8:164–71.  Back to cited text no. 10
    
11.
Gilkes DM, Semenza GL. Role of hypoxia-inducible factors in breast cancer metastasis. Future Oncol 2013;9:1623-36.  Back to cited text no. 11
    
12.
Maynard MA, Ohh M. The role of hypoxia-inducible factors in cancer. Cell Mol Life Sci 2007;64:2170-80.  Back to cited text no. 12
    


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