Expression of CYB561 in hepatocellular carcinoma and its clinical significance_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

DU Jingfang ¹ , YE Tao ² , HAO Ruiying ¹ , ZHUO Jian ² , LI Sha ³ , LIU Weiguang ⁴ ,  ZHANG Ruiying ⁵

1. Affiliated Hospital of Hebei University of Engineering, Handan, Hebei 056002, P. R. China;
2. Clinical School of Medicine, Hebei University of Engineering, Handan, Hebei 056002, P. R. China;
3. Department of Pathophysiology, Hebei University of Engineering, Handan, Hebei 056002, P. R. China;
4. Department of Breast Surgery, Yangzhou Maternal and Child Health Hospital, Yangzhou, Jiangsu 225007, P. R. China;
5. Department of Geriatrics, Affiliated Hospital of Hebei University of Engineering, Handan, Hebei 056002, P. R. China;

Corresponding author：

ZHANG Ruiying, Email: hbhdzry@163.com

Keywords：

hepatocellular carcinoma; cytochromes b561; immunohistochemistry; prognosis; survival analysis

DOI：

10.7507/1007-9424.202402028

Video：

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Objective To investigate the expression and clinical significance of cytochromes b561 (CYB561) in hepatocellular carcinoma (HCC). Methods The expression of CYB561 mRNA in HCC tissues and its relationship with prognosis were analyzed by database data. Immunohistochemistry (IHC) was used to detect the expression of CYB561 protein in 61 matched HCC tissues and their adjacent tissues, and the relationship between CYB561 protein expression and clinicopathological features and prognosis of HCC was analyzed. Kaplan-Meier method was used to draw the survival curve and Cox proportional hazard regression model was used to analyze the correlation between the expression of CYB561 protein and the prognosis of HCC. Results The analysis of database data showed that the relative expression of CYB561 mRNA in HCC tissues was higher than that in adjacent tissues (P<0.001). Compared with HCC patients with negative expression of CYB561 mRNA, HCC patients with positive expression of CYB561 mRNA had worse overall survival (OS), relapse-free survival, progression-free survival and disease-free survival (all P<0.05). The results of IHC showed that the positive rates of CYB561 protein in HCC tissues and adjacent tissues were 57.38% (35/61) and 21.31%(13/61), respectively. The former was higher than the latter, with statistical significance (χ²=16.624, P<0.001). Survival analysis showed that the OS of patients with positive expression of CYB561 protein was worse than that of patients with negative expression (P<0.05). Multivariate Cox proportional hazard regression analysis showed that the positive expression of CYB561 protein was a risk factor for postoperative OS in HCC patients [HR=3.308, 95%CI (1.344, 8.144), P=0.009]. Conclusion CYB561 is positively expressed in HCC and suggests a worse survival, and may serve as a potential prognostic biomarker for HCC.

Citation： DU Jingfang, YE Tao, HAO Ruiying, ZHUO Jian, LI Sha, LIU Weiguang, ZHANG Ruiying. Expression of CYB561 in hepatocellular carcinoma and its clinical significance. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2024, 31(8): 910-915. doi: 10.7507/1007-9424.202402028 Copy

1.	Llovet JM, Kelley RK, Villanueva A, et al. Hepatocellular carcinoma. Nat Rev Dis Primers, 2021, 7(1): 6. doi: 10.1038/s41572-020-00240-3.
2.	Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
3.	Zhang W, He H, Zang M, et al. Genetic features of aflatoxin-associated hepatocellular carcinoma. Gastroenterology, 2017, 153(1): 249-262.
4.	Kapiris I, Nastos K, Karakatsanis A, et al. Survivin expression in hepatocellular carcinoma. Correlation with clinicopathological characteristics and overall survival. J BUON, 2019, 24(5): 1934-1942.
5.	Zhang G, Li R, Deng Y, et al. Conditional survival of patients with hepatocellular carcinoma: results from the Surveillance, Epidemiology, and End Results registry. Expert Rev Gastroenterol Hepatol, 2018, 12(5): 515-523.
6.	McBride OW, Yi HF, Srivastava M. The human cytochrome b561 gene (CYB561) is located at 17q11-qter. Genomics, 1994, 21(3): 662-663.
7.	Bérczi A, Márton Z, Laskay K, et al. Spectral and redox properties of a recombinant mouse cytochrome b 561 protein suggest transmembrane electron transfer function. Molecules, 2023, 28(5): 2261. doi: 10.3390/molecules28052261.
8.	Polak ME, Thirdborough SM, Ung CY, et al. Distinct molecular signature of human skin Langerhans cells denotes critical differences in cutaneous dendritic cell immune regulation. J Invest Dermatol, 2014, 134(3): 695-703.
9.	Pruss RM, Shepard EA. Cytochrome b561 can be detected in many neuroendocrine tissues using a specific monoclonal antibody. Neuroscience, 1987, 22(1): 149-157.
10.	Zhang K, Deacon DC, Rao F, et al. Human heart rate: heritability of resting and stress values in twin pairs, and influence of genetic variation in the adrenergic pathway at a microribonucleic acid (microrna) motif in the 3′ -UTR of cytochrome b561 [corrected]. J Am Coll Cardiol, 2014, 63(4): 358-368.
11.	Willis S, Villalobos VM, Gevaert O, et al. Single gene prognostic biomarkers in ovarian cancer: a meta-analysis. PLoS One, 2016, 11(2): e0149183. doi: 10.1371/journal.pone.0149183.
12.	Zhou X, Shen G, Ren D, et al. Expression and clinical prognostic value of CYB561 in breast cancer. J Cancer Res Clin Oncol, 2022, 148(8): 1879-1892.
13.	Yang X, Zhao Y, Shao Q, et al. Cytochrome b561 serves as a potential prognostic biomarker and target for breast cancer. Int J Gen Med, 2021, 14: 10447-10464.
14.	Wang Z, Guo R, Trudeau SJ, et al. CYB561A3 is the key lysosomal iron reductase required for Burkitt B-cell growth and survival. Blood, 2021, 138(22): 2216-2230.
15.	Fan HL, Liu ST, Chang YL, et al. In vitro cell density determines the sensitivity of hepatocarcinoma cells to ascorbate. Front Oncol, 2022, 12: 843742. doi: 10.3389/fonc.2022.843742.
16.	Lane DJ, Bae DH, Merlot AM, et al. Duodenal cytochrome b (DCYTB) in iron metabolism: an update on function and regulation. Nutrients, 2015, 7(4): 2274-2296.
17.	Torti SV, Manz DH, Paul BT, et al. Iron and cancer. Annu Rev Nutr, 2018, 38: 97-125.
18.	Li L, Li Z, Qu J, et al. Novel long non-coding RNA CYB561-5 promotes aerobic glycolysis and tumorigenesis by interacting with basigin in non-small cell lung cancer. J Cell Mol Med, 2022, 26(5): 1402-1412.

1. Llovet JM, Kelley RK, Villanueva A, et al. Hepatocellular carcinoma. Nat Rev Dis Primers, 2021, 7(1): 6. doi: 10.1038/s41572-020-00240-3.
2. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
3. Zhang W, He H, Zang M, et al. Genetic features of aflatoxin-associated hepatocellular carcinoma. Gastroenterology, 2017, 153(1): 249-262.
4. Kapiris I, Nastos K, Karakatsanis A, et al. Survivin expression in hepatocellular carcinoma. Correlation with clinicopathological characteristics and overall survival. J BUON, 2019, 24(5): 1934-1942.
5. Zhang G, Li R, Deng Y, et al. Conditional survival of patients with hepatocellular carcinoma: results from the Surveillance, Epidemiology, and End Results registry. Expert Rev Gastroenterol Hepatol, 2018, 12(5): 515-523.
6. McBride OW, Yi HF, Srivastava M. The human cytochrome b561 gene (CYB561) is located at 17q11-qter. Genomics, 1994, 21(3): 662-663.
7. Bérczi A, Márton Z, Laskay K, et al. Spectral and redox properties of a recombinant mouse cytochrome b 561 protein suggest transmembrane electron transfer function. Molecules, 2023, 28(5): 2261. doi: 10.3390/molecules28052261.
8. Polak ME, Thirdborough SM, Ung CY, et al. Distinct molecular signature of human skin Langerhans cells denotes critical differences in cutaneous dendritic cell immune regulation. J Invest Dermatol, 2014, 134(3): 695-703.
9. Pruss RM, Shepard EA. Cytochrome b561 can be detected in many neuroendocrine tissues using a specific monoclonal antibody. Neuroscience, 1987, 22(1): 149-157.
10. Zhang K, Deacon DC, Rao F, et al. Human heart rate: heritability of resting and stress values in twin pairs, and influence of genetic variation in the adrenergic pathway at a microribonucleic acid (microrna) motif in the 3′ -UTR of cytochrome b561 [corrected]. J Am Coll Cardiol, 2014, 63(4): 358-368.
11. Willis S, Villalobos VM, Gevaert O, et al. Single gene prognostic biomarkers in ovarian cancer: a meta-analysis. PLoS One, 2016, 11(2): e0149183. doi: 10.1371/journal.pone.0149183.
12. Zhou X, Shen G, Ren D, et al. Expression and clinical prognostic value of CYB561 in breast cancer. J Cancer Res Clin Oncol, 2022, 148(8): 1879-1892.
13. Yang X, Zhao Y, Shao Q, et al. Cytochrome b561 serves as a potential prognostic biomarker and target for breast cancer. Int J Gen Med, 2021, 14: 10447-10464.
14. Wang Z, Guo R, Trudeau SJ, et al. CYB561A3 is the key lysosomal iron reductase required for Burkitt B-cell growth and survival. Blood, 2021, 138(22): 2216-2230.
15. Fan HL, Liu ST, Chang YL, et al. In vitro cell density determines the sensitivity of hepatocarcinoma cells to ascorbate. Front Oncol, 2022, 12: 843742. doi: 10.3389/fonc.2022.843742.
16. Lane DJ, Bae DH, Merlot AM, et al. Duodenal cytochrome b (DCYTB) in iron metabolism: an update on function and regulation. Nutrients, 2015, 7(4): 2274-2296.
17. Torti SV, Manz DH, Paul BT, et al. Iron and cancer. Annu Rev Nutr, 2018, 38: 97-125.
18. Li L, Li Z, Qu J, et al. Novel long non-coding RNA CYB561-5 promotes aerobic glycolysis and tumorigenesis by interacting with basigin in non-small cell lung cancer. J Cell Mol Med, 2022, 26(5): 1402-1412.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Expression of CYB561 in hepatocellular carcinoma and its clinical significance

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