Predictive value of alpha fetoprotein expression in chemoresistance of hepatocellular carcinoma_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

SUN Han ¹ , CHEN Wu ² , WANG Yun ² ,  WANG Yiqiu ² , RAO Jianhua ³ , LIU Xia ⁴ , LIU Peng ² , TIAN Qingzhong ²

1. Department of Gastroenterology, The Affiliated Xuzhou Hospital of Medical College of Southeast University, Xuzhou, Jiangsu 221009, P. R. China;
2. Department of Surgical Oncology, Southeast University Cancer Institute (Xuzhou), The Affiliated Xuzhou Hospital of Medical College of Southeast University, Xuzhou, Jiangsu 221009, P. R. China;
3. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, P. R. China;
4. Department of Pathology, The Affiliated Xuzhou Hospital of Medical College of Southeast University, Xuzhou, Jiangsu 221009, P. R. China;

Corresponding author：

WANG Yiqiu, Email: truemanwyq@sina.com

Keywords：

Hepatocellular carcinoma; Alpha fetoprotein; Chemotherapeutic resistance

DOI：

10.7507/1007-9424.201811053

Video：

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Objective To evaluate the relationship between the expression of alpha fetoprotein (AFP) and chemoresistance in hepatocellular carcinoma.Methods Hepatocellular carcinoma was screened from liver tumor tissue samples, which was obtained by puncture before transcatheter arterial chemoembolization (TACE). Immuno-histochemical staining was used to detect the expression of AFP in HCC tissues and the effect of AFP expression in HCC on the effect of chemotherapy was analyzed.Results A total of 62 patients met the inclusion criteria, of which 36 were in the chemotherapy resistant group and 26 in the chemotherapy sensitive group. There were 42 patients with positive expression of AFP in tumor tissues (including 29 patients with chemoresistance) and 20 patients with negative expression of AFP in tumor tissues (including 7 patients with chemoresistance). There were no significant difference between the two groups in sex, age, tumor differentiation, Child-Pugh classification of liver function, tumor size, tumor site and hepatitis (P>0.05). In elevated serum AFP level, tumor single, and with portal vein tumor thrombus (PVTT), the proportion of patients in the chemosensitivity group were significantly lower than that in the chemosensitivity group (P<0.05). The results of logistic multivariate regression analysis showed that positive expression of AFP ［OR=0.280, 95%CI (0.092, 0.950), P=0.045］ and PVTT ［OR=0.026, 95%CI (0.004, 0.322), P=0.005］ were independent risk factors for chemotherapeutic resistance in hepatocellular carcinoma.Conclusion AFP positive expression in liver tumor tissues and PVTT are useful indicators of resistance to chemotherapy.

Citation： SUN Han, CHEN Wu, WANG Yun, WANG Yiqiu, RAO Jianhua, LIU Xia, LIU Peng, TIAN Qingzhong. Predictive value of alpha fetoprotein expression in chemoresistance of hepatocellular carcinoma. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2019, 26(4): 432-437. doi: 10.7507/1007-9424.201811053 Copy

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8.	Halbrecht I, Klibanski C. Identification of a new normal embryonic haemoglobin. Nature, 1956, 178(4537): 794-795.
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12.	梅英, 杜伟, 丁雄, 等. 靶向重组腺病毒载体逆转肝癌细胞多药耐药的实验研究. 第三军医大学学报, 2009, 31(15): 1462-1466.
13.	Nagao M, Nakajima Y, Kanehiro H, et al. The Impact of interferon gamma receptor expression on the mechanism of escape from host immune surveillance in hepatocellular carcinoma. Hepatology, 2010, 32(3): 491-500.
14.	Hahne M, Rimoldi D, Schröter M, et al. Melanoma cell expression of Fas (Apo-1/CD95) ligand: implications for tumor immune escape. Science, 1996, 274(5291): 1363-1366.
15.	Patel T. Immune escape in hepatocellular cancer: is a good offense the best defense? Hepatology, 1999, 30(2): 576-578.
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19.	朱明月, 郭峻莉, 夏华, 等. 甲胎蛋白激活 PI3K/AKT 信号促使肝癌 Bel 7402 细胞抗全反式维甲酸诱导凋亡. 中华肝脏病杂志, 2014, 22(11): 837-842.
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22.	Li M, Zhu M, Li W, et al. Alpha-fetoprotein receptor as an early indicator of HBx-driven hepatocarcinogenesis and its applications in tracing cancer cell metastasis. Cancer Letters, 2013, 330(2): 170-180.
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24.	李孟森, 詹志农, 周升, 等. 甲胎蛋白对人肝癌 Bel 7402 细胞 caspase 信号传递及耐受 TRAIL 的影响. 西安交通大学学报 (医学版), 2009, 30(2): 159-168.
25.	童颖, 杨甲梅, 徐峰, 等. 原发性肝癌伴门静脉癌栓行术后肝动脉化疗栓塞联合门静脉化疗的疗效观察. 中华肝胆外科杂志, 2008, 14(12): 851-853.
26.	Zhu H, Chen XP, Luo SF, et al. Involvement of hypoxia-inducible factor-1-alpha in multidrug resistance induced by hypoxia in HepG2 cells. J Exp Clin Cancer Res, 2005, 24(4): 565-574.
27.	Liang Y, Zheng T, Song R, et al. Hypoxia-mediated sorafenib resistance can be overcome by EF24 through Von Hippel-Lindau tumor suppressor-dependent HIF-1α inhibition in hepatocellular carcinoma. Hepatology, 2013, 57(5): 1847-1857.

1. Ferenci P, Fried M, Labrecque D, et al. Hepatocellular carcinoma (HCC): a global perspective. J Clin Gastroenterol, 2010, 44(4): 239-245.
2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin, 2018, 68(1): 7-30.
3. Rigalli JP, Ciriaci N, Arias A, et al. Regulation of multidrug resistance proteins by genistein in a hepatocarcinoma cell line: impact on sorafenib cytotoxicity. Plos One, 2015, 10(3): e0119502.
4. Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol, 2010, 17(6): 1471-1474.
5. Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol, 1982, 5(6): 649-655.
6. Bruix J, Sherman M, Llovet JM, et al. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol, 2001, 35(3): 421-430.
7. 余文昌, 张孔志, 陈示光, 等. 实体瘤反应评价标准、欧洲肝病学会和改良实体瘤反应评价标准评价原发性肝癌化疗栓塞效果一致性的比较. 中华放射学杂志, 2011, 45(8): 766-769.
8. Halbrecht I, Klibanski C. Identification of a new normal embryonic haemoglobin. Nature, 1956, 178(4537): 794-795.
9. Tatarinov YS. New data on the embryo-specific antigenic components of human blood serum. Fed Proc Transl Suppl, 1965, 24(5): 916-918.
10. Kosuge T, Makuuchi M, Takayama T, et al. Long-term results after resection of hepatocellular carcinoma: experience of 480 cases. Hepatogastroenterology, 1993, 40(4): 328-332.
11. 吴超, 杨健, 张金玲, 等. 甲胎蛋白对耐药基因 MDR1 表达及肝癌细胞化疗敏感性的影响. 中华肝胆外科杂志, 2015, 21(12): 811-815.
12. 梅英, 杜伟, 丁雄, 等. 靶向重组腺病毒载体逆转肝癌细胞多药耐药的实验研究. 第三军医大学学报, 2009, 31(15): 1462-1466.
13. Nagao M, Nakajima Y, Kanehiro H, et al. The Impact of interferon gamma receptor expression on the mechanism of escape from host immune surveillance in hepatocellular carcinoma. Hepatology, 2010, 32(3): 491-500.
14. Hahne M, Rimoldi D, Schröter M, et al. Melanoma cell expression of Fas (Apo-1/CD95) ligand: implications for tumor immune escape. Science, 1996, 274(5291): 1363-1366.
15. Patel T. Immune escape in hepatocellular cancer: is a good offense the best defense? Hepatology, 1999, 30(2): 576-578.
16. Hoffman WH, Biade S, Zilfou JT, et al. Transcriptional repression of the anti-apoptotic survivin gene by wild type p53. J Biol Chem, 2002, 277(5): 3247-3257.
17. Steck PA, Pershouse MA, Jasser SA, et al. Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nature Genetics, 1997, 15(4): 356-362.
18. Li J, Yen C, Liaw D, et al. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science, 1997, 275(5308): 1943-1947.
19. 朱明月, 郭峻莉, 夏华, 等. 甲胎蛋白激活 PI3K/AKT 信号促使肝癌 Bel 7402 细胞抗全反式维甲酸诱导凋亡. 中华肝脏病杂志, 2014, 22(11): 837-842.
20. Li MS, Li PF, He SP, et al. The promoting molecular mechanism of alpha-fetoprotein on the growth of human hepatoma Bel7402 cell line. World J Gastroenterol, 2002, 8(3): 469-475.
21. Li MS, Li PF, Chen Q, et al. Alpha-fetoprotein stimulated the expression of some oncogenes in human hepatocellular carcinoma Bel 7402 cells. World J Gastroenterol, 2004, 10(6): 819-824.
22. Li M, Zhu M, Li W, et al. Alpha-fetoprotein receptor as an early indicator of HBx-driven hepatocarcinogenesis and its applications in tracing cancer cell metastasis. Cancer Letters, 2013, 330(2): 170-180.
23. Li M, Li H, Li C, et al. Alpha fetoprotein is a novel protein-binding partner for caspase-3 and blocks the apoptotic signaling pathway in human hepatoma cells. Int J Cancer, 2010, 124(12): 2845-2854.
24. 李孟森, 詹志农, 周升, 等. 甲胎蛋白对人肝癌 Bel 7402 细胞 caspase 信号传递及耐受 TRAIL 的影响. 西安交通大学学报 (医学版), 2009, 30(2): 159-168.
25. 童颖, 杨甲梅, 徐峰, 等. 原发性肝癌伴门静脉癌栓行术后肝动脉化疗栓塞联合门静脉化疗的疗效观察. 中华肝胆外科杂志, 2008, 14(12): 851-853.
26. Zhu H, Chen XP, Luo SF, et al. Involvement of hypoxia-inducible factor-1-alpha in multidrug resistance induced by hypoxia in HepG2 cells. J Exp Clin Cancer Res, 2005, 24(4): 565-574.
27. Liang Y, Zheng T, Song R, et al. Hypoxia-mediated sorafenib resistance can be overcome by EF24 through Von Hippel-Lindau tumor suppressor-dependent HIF-1α inhibition in hepatocellular carcinoma. Hepatology, 2013, 57(5): 1847-1857.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Predictive value of alpha fetoprotein expression in chemoresistance of hepatocellular carcinoma

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