Research progress on relationship between metabolic syndrome and hepatocellular carcinoma and its mechanism_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

CHEN Xiaobin ¹ , GAO Shuai ¹ , MEI Xuepeng ¹ , XU Zhaojun ² , WANG Zhixin ^1,3 , XU He ¹ , WANG Haijiu ^1,3 ,  FAN Haining ^1,3

1. Department of Hepatopancreatobiliary Surgery, Affiliated Hospital of Qinghai University, Xining 810001, P. R. China;
2. Department of Gastrointestinal Surgery, Affiliated Hospital of Qinghai University, Xining 810001, P. R. China;
3. Key Laboratory of Hydatid Diseases of Qinghai Province, Xining 810001, P. R. China;

Corresponding author：

FAN Haining, Email: fanhaining@medmail.com.cn

Keywords：

metabolic syndrome; hepatocellular carcinoma; risk factor

DOI：

10.7507/1007-9424.202009091

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To understand the relationship between obesity, hyperglycemia, hypertension, and lipid metabolism disorder in metabolic syndrome and hepatocellular carcinoma (HCC), and to provide reference for screening, diagnosis, treatment, and prevention of HCC in clinic.Method The related literatures about the relationship between metabolic syndrome related factors (obesity, hyperglycemia, hypertension, and lipid metabolism disorder) and HCC were searched and summarized.Results Obesity, hyperglycemia, hypertension, and abnormal lipid metabolism in metabolic syndrome were closely related to HCC, which were the high risk factors for leading to HCC, indicating that metabolic syndrome was closely related to the risk of HCC.Conclusions Metabolic syndrome is closely related to the risk of HCC. It is of great significance for screening, diagnosis, treatment, and prevention of HCC to deeply understand the mechanism and determinants of HCC caused by metabolic syndrome.

Citation： CHEN Xiaobin, GAO Shuai, MEI Xuepeng, XU Zhaojun, WANG Zhixin, XU He, WANG Haijiu, FAN Haining. Research progress on relationship between metabolic syndrome and hepatocellular carcinoma and its mechanism. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2021, 28(7): 969-973. doi: 10.7507/1007-9424.202009091 Copy

1.	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.
2.	Ferlay J, Colombet M, Soerjomataram I, et al. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int J Cancer, 2019, 144(8): 1941-1953.
3.	Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin, 2019, 69(1): 7-34.
4.	任会娜, 黄文祥. 代谢综合征与肝脏相关事件的关系—系统回顾与meta分析. 重庆: 重庆医科大学, 2019.
5.	Reaven GM. Role of insulin resistance in human disease//Gotto AM, Lenfant C, Paoletti R, et al. Eds. Multiple risk factors in cardiovascular disease. Medical Science Symposia Series. Dordrecht: Springer, 1992.
6.	中华医学会糖尿病学分会. 中国 2 型糖尿病防治指南(2017 年版). 中华糖尿病杂志, 2018, 10(1): 4-67.
7.	梁晓峰, 李利娟, 刘俊田. 代谢综合征与胃癌发病风险及临床病理特征相关性的研究. 中国肿瘤临床, 2019, 46(19): 986-993.
8.	陈涛, 邢雪. 代谢综合征与胰腺癌的发生、恶性程度及预后的关系研究. 大连: 大连医科大学, 2018.
9.	杨小康, 徐光勇. 代谢综合征与前列腺癌的相关性研究. 重庆: 重庆医科大学, 2020.
10.	陈瑾歆, 陈建业. 代谢综合征发病机制的研究进展. 川北医学院学报, 2008, 23(4): 409-414.
11.	Zimmet P, Magliano D, Matsuzawa Y, et al. The metabolic syndrome: a global public health problem and a new definition. J Atheroscler Thromb, 2005, 12(6): 295-300.
12.	姜蔚. 肥胖促进肿瘤发生发展的相关机制研究进展. 中国慢性病预防与控制, 2020, 28(2): 154-158.
13.	Bhaskaran K, Douglas I, Forbes H, et al. Body-mass index and risk of 22 specific cancers: a population-based cohort study of 5.24 million UK adults. Lancet, 2014, 384(9945): 755-765.
14.	Cheung OK, Cheng AS. Gender differences in adipocyte metabolism and liver cancer progression. Front Genet, 2016, 7: 168.
15.	谢锐, 梁红亮, 杨舒钧, 等. 体质量指数与肝癌患者临床病理特征及预后关系. 临床军医杂志, 2020, 48(3): 347-348, 351.
16.	林伟寅, 侯金林, 孙剑. 超重和肥胖对慢性乙型肝炎患者肝脏炎症及肝癌的影响. 广州: 南方医科大学, 2019.
17.	Nair S, Mason A, Eason J, et al. Is obesity an independent risk factor for hepatocellular carcinoma in cirrhosis? Hepatology, 2002, 36(1): 150-155.
18.	Karagozian R, Derdák Z, Baffy G. Obesity-associated mechanisms of hepatocarcinogenesis. Metabolism, 2014, 63(5): 607-617.
19.	Marengo A, Rosso C, Bugianesi E. Liver cancer: connections with obesity, fatty liver, and cirrhosis. Annu Rev Med, 2016, 67: 103-117.
20.	Deng T, Lyon CJ, Bergin S, et al. Obesity, inflammation, and cancer. Annu Rev Pathol, 2016, 11: 421-449.
21.	Iyengar NM, Hudis CA, Dannenberg AJ. Obesity and cancer: local and systemic mechanisms. Annu Rev Med, 2015, 66: 297-309.
22.	Chen Y, Zhang F, Zhao Y, et al. Obesity-associated miR-27a upregulation promotes hepatocellular carcinoma metastasis through suppressing SFRP1. Onco Targets Ther, 2018, 11: 3281-3292.
23.	王林, 曹红, 庞雪利, 等. 瘦素对人乳腺癌 MCF-7 细胞迁移和侵袭的影响及其机制. 细胞与分子免疫学杂志, 2013, 29(12): 1272-1276.
24.	Dalamaga M, Diakopoulos KN, Mantzoros CS. The role of adiponectin in cancer: a review of current evidence. Endocr Rev, 2012, 33(4): 547-594.
25.	Katira A, Tan PH. Evolving role of adiponectin in cancer-controversies and update. Cancer Biol Med, 2016, 13(1): 101-119.
26.	Loo TM, Kamachi F, Watanabe Y, et al. Gut microbiota promotes obesity-associated liver cancer through PGE2-mediated suppression of antitumor immunity. Cancer Discov, 2017, 7(5): 522-538.
27.	Djuric Z. Obesity-associated cancer risk: the role of intestinal microbiota in the etiology of the host proinflammatory state. Transl Res, 2017, 179: 155-167.
28.	Gao C, Yao SK. Diabetes mellitus: a “true” independent risk factor for hepatocellular carcinoma? Hepatobiliary Pancreat Dis Int, 2009, 8(5): 465-473.
29.	Longato L, de la Monte S, Kuzushita N, et al. Overexpression of insulin receptor substrate-1 and hepatitis Bx genes causes premalignant alterations in the liver. Hepatology, 2009, 49(6): 1935-1943.
30.	Wideroff L, Gridley G, Mellemkjaer L, et al. Cancer incidence in a population-based cohort of patients hospitalized with diabetes mellitus in Denmark. J Natl Cancer Inst, 1997, 89(18): 1360-1365.
31.	Feng X, Wang G, Li N, et al. The association between fasting blood glucose and the risk of primary liver cancer in Chinese males: a population-based prospective study. Br J Cancer, 2017, 117(9): 1405-1411.
32.	Simon TG, King LY, Chong DQ, et al. Diabetes, metabolic comorbidities, and risk of hepatocellular carcinoma: Results from two prospective cohort studies. Hepatology, 2018, 67(5): 1797-1806.
33.	Hosokawa T, Kurosaki M, Tsuchiya K, et al. Hyperglycemia is a significant prognostic factor of hepatocellular carcinoma after curative therapy. World J Gastroenterol, 2013, 19(2): 249-257.
34.	Li X, Xu H, Gao P. Diabetes mellitus is a risk factor for hepatocellular carcinoma in patients with chronic hepatitis B virus infection in China. Med Sci Monit, 2018, 24: 6729-6734.
35.	Zheng Z, Zhang C, Yan J, et al. Diabetes mellitus is associated with hepatocellular carcinoma: a retrospective case-control study in hepatitis endemic area. PLoS One, 2013, 8(12): e84776.
36.	Jabir NR, Ahmad S, Tabrez S. An insight on the association of glycation with hepatocellular carcinoma. Semin Cancer Biol, 2018, 49: 56-63.
37.	Buzzai M, Bauer DE, Jones RG, et al. The glucose dependence of Akt-transformed cells can be reversed by pharmacologic activation of fatty acid beta-oxidation. Oncogene, 2005, 24(26): 4165-4173.
38.	Wang Q, Yu WN, Chen X, et al. Spontaneous hepatocellular carcinoma after the combined deletion of Akt isoforms. Cancer Cell, 2016, 29(4): 523-535.
39.	Raj PN, Shaji BV, Haritha VH, et al. Neutrophil secretion modulates neutrophil and monocyte functions during hyperglucose and/or hyperinsulin conditions in vitro. J Cell Immunothera, 2018, 4(2): 65-70.
40.	Fainsod-Levi T, Gershkovitz M, Völs S, et al. Hyperglycemia impairs neutrophil mobilization leading to enhanced metastatic seeding. Cell Rep, 2017, 21(9): 2384-2392.
41.	Tay HM, Dalan R, Li KHH, et al. A novel microdevice for rapid neutrophil purification and phenotyping in type 2 diabetes mellitus. Small, 2017, 14(6): 1702832.
42.	Wang Z, Wei M, Wang M, et al. Inhibition of macrophage migration inhibitory factor reduces diabetic nephropathy in type Ⅱ diabetes mice. Inflammation, 2014, 37(6): 2020-2029.
43.	Yong SB, Song Y, Kim YH. Visceral adipose tissue macrophage-targeted TACE silencing to treat obesity-induced type 2 diabetes. Biomaterials, 2017, 148: 81-89.
44.	Ward PS, Thompson CB. Metabolic reprogramming: a cancer hallmark even Warburg did not anticipate. Cancer Cell, 2012, 21(3): 297-308.
45.	Jia G, Sowers JR. Targeting CITED2 for angiogenesis in obesity and insulin resistance. Diabetes, 2016, 65(12): 3535-3536.
46.	Giovannucci E, Harlan DM, Archer MC, et al. Diabetes and cancer: a consensus report. Diabetes Care, 2010, 33(7): 1674-1685.
47.	Xie L, Wu K, Xu N, et al. Hypertension is associated with a high risk of cancer. J Hum Hypertens, 1999, 13(5): 295-301.
48.	谢良地, 吴可贵, 许能锋, 等. 高血压病人发生肿瘤危险性的研究. 高血压杂志, 1998, 6(4): 18-22.
49.	Welzel TM, Graubard BI, Zeuzem S, et al. Metabolic syndrome increases the risk of primary liver cancer in the United States: a study in the SEER-Medicare database. Hepatology, 2011, 54(2): 463-471.
50.	Goon PK, Stonelake PS, Lip GY. Hypertension, anti-hypertensive therapy and neoplasia. Curr Pharm Des, 2007, 13(25): 2539-2544.
51.	Turati F, Talamini R, Pelucchi C, et al. Metabolic syndrome and hepatocellular carcinoma risk. Br J Cancer, 2013, 108(1): 222-228.
52.	Koene RJ, Prizment AE, Blaes A, et al. Shared risk factors in cardiovascular disease and cancer. Circulation, 2016, 133(11): 1104-1114.
53.	Ferrara N. VEGF and the quest for tumour angiogenesis factors. Nat Rev Cancer, 2002, 2(10): 795-803.
54.	Kang YS, Park YG, Kim BK, et al. Angiotensin Ⅱ stimulates the synthesis of vascular endothelial growth factor through the p38 mitogen activated protein kinase pathway in cultured mouse podocytes. J Mol Endocrinol, 2006, 36(2): 377-388.
55.	Matsuda M, Shimomura I. Increased oxidative stress in obesity: implications for metabolic syndrome, diabetes, hypertension, dyslipidemia, atherosclerosis, and cancer. Obes Res Clin Pract, 2013, 7(5): e330-e341.
56.	Ishino K, Mutoh M, Totsuka Y, et al. Metabolic syndrome: a novel high-risk state for colorectal cancer. Cancer Lett, 2013, 334(1): 56-61.
57.	李师, 杜少辉. 原发性肝癌中医证型与脂代谢的分析. 广州: 广州中医药大学, 2018.
58.	Li Z, Guan M, Lin Y, et al. Aberrant lipid metabolism in hepatocellular carcinoma revealed by liver lipidomics. Int J Mol Sci, 2017, 18(12): 2550.
59.	Lu M, Hu XH, Li Q, et al. A specific cholesterol metabolic pathway is established in a subset of HCCs for tumor growth. J Mol Cell Biol, 2013, 5(6): 404-415.
60.	Krautbauer S, Weiss TS, Wiest R, et al. Diagnostic value of systemic cholesteryl ester/free cholesterol ratio in hepatocellular carcinoma. Anticancer Res, 2017, 37(7): 3527-3535.
61.	Kitahara CM, Berrington de González A, Freedman ND, et al. Total cholesterol and cancer risk in a large prospective study in Korea. J Clin Oncol, 2011, 29(12): 1592-1598.
62.	张俊国, 栾芳. 胆固醇在肝细胞肝癌分级和转移中作用的初步研究. 济南: 山东大学, 2016.
63.	Mieno MN, Sawabe M, Tanaka N, et al. Significant association between hypolipoproteinemia(a) and lifetime risk of cancer: an autopsy study from a community-based Geriatric Hospital. Cancer Epidemiol, 2014, 38(5): 550-555.
64.	Win AK, Macinnis RJ, Hopper JL, et al. Risk prediction models for colorectal cancer: a review. Cancer Epidemiol Biomarkers Prev, 2012, 21(3): 398-410.
65.	Liu CS, Hsu HS, Li CI, et al. Central obesity and atherogenic dyslipidemia in metabolic syndrome are associated with increased risk for colorectal adenoma in a Chinese population. BMC Gastroenterol, 2010, 10: 51.
66.	Liu X, Liang Y, Song R, Yang G, et al. Long non-coding RNA NEAT1-modulated abnormal lipolysis via ATGL drives hepatocellular carcinoma proliferation. Mol Cancer, 2018, 17(1): 90.
67.	Che L, Chi W, Qiao Y, et al. Cholesterol biosynthesis supports the growth of hepatocarcinoma lesions depleted of fatty acid synthase in mice and humans. Gut, 2020, 69(1): 177-186.
68.	郭佩, 胡玉琳. 代谢综合征与原发性肝细胞癌的相关性研究. 长春: 吉林大学, 2017.

1. 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.
2. Ferlay J, Colombet M, Soerjomataram I, et al. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int J Cancer, 2019, 144(8): 1941-1953.
3. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin, 2019, 69(1): 7-34.
4. 任会娜, 黄文祥. 代谢综合征与肝脏相关事件的关系—系统回顾与meta分析. 重庆: 重庆医科大学, 2019.
5. Reaven GM. Role of insulin resistance in human disease//Gotto AM, Lenfant C, Paoletti R, et al. Eds. Multiple risk factors in cardiovascular disease. Medical Science Symposia Series. Dordrecht: Springer, 1992.
6. 中华医学会糖尿病学分会. 中国 2 型糖尿病防治指南(2017 年版). 中华糖尿病杂志, 2018, 10(1): 4-67.
7. 梁晓峰, 李利娟, 刘俊田. 代谢综合征与胃癌发病风险及临床病理特征相关性的研究. 中国肿瘤临床, 2019, 46(19): 986-993.
8. 陈涛, 邢雪. 代谢综合征与胰腺癌的发生、恶性程度及预后的关系研究. 大连: 大连医科大学, 2018.
9. 杨小康, 徐光勇. 代谢综合征与前列腺癌的相关性研究. 重庆: 重庆医科大学, 2020.
10. 陈瑾歆, 陈建业. 代谢综合征发病机制的研究进展. 川北医学院学报, 2008, 23(4): 409-414.
11. Zimmet P, Magliano D, Matsuzawa Y, et al. The metabolic syndrome: a global public health problem and a new definition. J Atheroscler Thromb, 2005, 12(6): 295-300.
12. 姜蔚. 肥胖促进肿瘤发生发展的相关机制研究进展. 中国慢性病预防与控制, 2020, 28(2): 154-158.
13. Bhaskaran K, Douglas I, Forbes H, et al. Body-mass index and risk of 22 specific cancers: a population-based cohort study of 5.24 million UK adults. Lancet, 2014, 384(9945): 755-765.
14. Cheung OK, Cheng AS. Gender differences in adipocyte metabolism and liver cancer progression. Front Genet, 2016, 7: 168.
15. 谢锐, 梁红亮, 杨舒钧, 等. 体质量指数与肝癌患者临床病理特征及预后关系. 临床军医杂志, 2020, 48(3): 347-348, 351.
16. 林伟寅, 侯金林, 孙剑. 超重和肥胖对慢性乙型肝炎患者肝脏炎症及肝癌的影响. 广州: 南方医科大学, 2019.
17. Nair S, Mason A, Eason J, et al. Is obesity an independent risk factor for hepatocellular carcinoma in cirrhosis? Hepatology, 2002, 36(1): 150-155.
18. Karagozian R, Derdák Z, Baffy G. Obesity-associated mechanisms of hepatocarcinogenesis. Metabolism, 2014, 63(5): 607-617.
19. Marengo A, Rosso C, Bugianesi E. Liver cancer: connections with obesity, fatty liver, and cirrhosis. Annu Rev Med, 2016, 67: 103-117.
20. Deng T, Lyon CJ, Bergin S, et al. Obesity, inflammation, and cancer. Annu Rev Pathol, 2016, 11: 421-449.
21. Iyengar NM, Hudis CA, Dannenberg AJ. Obesity and cancer: local and systemic mechanisms. Annu Rev Med, 2015, 66: 297-309.
22. Chen Y, Zhang F, Zhao Y, et al. Obesity-associated miR-27a upregulation promotes hepatocellular carcinoma metastasis through suppressing SFRP1. Onco Targets Ther, 2018, 11: 3281-3292.
23. 王林, 曹红, 庞雪利, 等. 瘦素对人乳腺癌 MCF-7 细胞迁移和侵袭的影响及其机制. 细胞与分子免疫学杂志, 2013, 29(12): 1272-1276.
24. Dalamaga M, Diakopoulos KN, Mantzoros CS. The role of adiponectin in cancer: a review of current evidence. Endocr Rev, 2012, 33(4): 547-594.
25. Katira A, Tan PH. Evolving role of adiponectin in cancer-controversies and update. Cancer Biol Med, 2016, 13(1): 101-119.
26. Loo TM, Kamachi F, Watanabe Y, et al. Gut microbiota promotes obesity-associated liver cancer through PGE2-mediated suppression of antitumor immunity. Cancer Discov, 2017, 7(5): 522-538.
27. Djuric Z. Obesity-associated cancer risk: the role of intestinal microbiota in the etiology of the host proinflammatory state. Transl Res, 2017, 179: 155-167.
28. Gao C, Yao SK. Diabetes mellitus: a “true” independent risk factor for hepatocellular carcinoma? Hepatobiliary Pancreat Dis Int, 2009, 8(5): 465-473.
29. Longato L, de la Monte S, Kuzushita N, et al. Overexpression of insulin receptor substrate-1 and hepatitis Bx genes causes premalignant alterations in the liver. Hepatology, 2009, 49(6): 1935-1943.
30. Wideroff L, Gridley G, Mellemkjaer L, et al. Cancer incidence in a population-based cohort of patients hospitalized with diabetes mellitus in Denmark. J Natl Cancer Inst, 1997, 89(18): 1360-1365.
31. Feng X, Wang G, Li N, et al. The association between fasting blood glucose and the risk of primary liver cancer in Chinese males: a population-based prospective study. Br J Cancer, 2017, 117(9): 1405-1411.
32. Simon TG, King LY, Chong DQ, et al. Diabetes, metabolic comorbidities, and risk of hepatocellular carcinoma: Results from two prospective cohort studies. Hepatology, 2018, 67(5): 1797-1806.
33. Hosokawa T, Kurosaki M, Tsuchiya K, et al. Hyperglycemia is a significant prognostic factor of hepatocellular carcinoma after curative therapy. World J Gastroenterol, 2013, 19(2): 249-257.
34. Li X, Xu H, Gao P. Diabetes mellitus is a risk factor for hepatocellular carcinoma in patients with chronic hepatitis B virus infection in China. Med Sci Monit, 2018, 24: 6729-6734.
35. Zheng Z, Zhang C, Yan J, et al. Diabetes mellitus is associated with hepatocellular carcinoma: a retrospective case-control study in hepatitis endemic area. PLoS One, 2013, 8(12): e84776.
36. Jabir NR, Ahmad S, Tabrez S. An insight on the association of glycation with hepatocellular carcinoma. Semin Cancer Biol, 2018, 49: 56-63.
37. Buzzai M, Bauer DE, Jones RG, et al. The glucose dependence of Akt-transformed cells can be reversed by pharmacologic activation of fatty acid beta-oxidation. Oncogene, 2005, 24(26): 4165-4173.
38. Wang Q, Yu WN, Chen X, et al. Spontaneous hepatocellular carcinoma after the combined deletion of Akt isoforms. Cancer Cell, 2016, 29(4): 523-535.
39. Raj PN, Shaji BV, Haritha VH, et al. Neutrophil secretion modulates neutrophil and monocyte functions during hyperglucose and/or hyperinsulin conditions in vitro. J Cell Immunothera, 2018, 4(2): 65-70.
40. Fainsod-Levi T, Gershkovitz M, Völs S, et al. Hyperglycemia impairs neutrophil mobilization leading to enhanced metastatic seeding. Cell Rep, 2017, 21(9): 2384-2392.
41. Tay HM, Dalan R, Li KHH, et al. A novel microdevice for rapid neutrophil purification and phenotyping in type 2 diabetes mellitus. Small, 2017, 14(6): 1702832.
42. Wang Z, Wei M, Wang M, et al. Inhibition of macrophage migration inhibitory factor reduces diabetic nephropathy in type Ⅱ diabetes mice. Inflammation, 2014, 37(6): 2020-2029.
43. Yong SB, Song Y, Kim YH. Visceral adipose tissue macrophage-targeted TACE silencing to treat obesity-induced type 2 diabetes. Biomaterials, 2017, 148: 81-89.
44. Ward PS, Thompson CB. Metabolic reprogramming: a cancer hallmark even Warburg did not anticipate. Cancer Cell, 2012, 21(3): 297-308.
45. Jia G, Sowers JR. Targeting CITED2 for angiogenesis in obesity and insulin resistance. Diabetes, 2016, 65(12): 3535-3536.
46. Giovannucci E, Harlan DM, Archer MC, et al. Diabetes and cancer: a consensus report. Diabetes Care, 2010, 33(7): 1674-1685.
47. Xie L, Wu K, Xu N, et al. Hypertension is associated with a high risk of cancer. J Hum Hypertens, 1999, 13(5): 295-301.
48. 谢良地, 吴可贵, 许能锋, 等. 高血压病人发生肿瘤危险性的研究. 高血压杂志, 1998, 6(4): 18-22.
49. Welzel TM, Graubard BI, Zeuzem S, et al. Metabolic syndrome increases the risk of primary liver cancer in the United States: a study in the SEER-Medicare database. Hepatology, 2011, 54(2): 463-471.
50. Goon PK, Stonelake PS, Lip GY. Hypertension, anti-hypertensive therapy and neoplasia. Curr Pharm Des, 2007, 13(25): 2539-2544.
51. Turati F, Talamini R, Pelucchi C, et al. Metabolic syndrome and hepatocellular carcinoma risk. Br J Cancer, 2013, 108(1): 222-228.
52. Koene RJ, Prizment AE, Blaes A, et al. Shared risk factors in cardiovascular disease and cancer. Circulation, 2016, 133(11): 1104-1114.
53. Ferrara N. VEGF and the quest for tumour angiogenesis factors. Nat Rev Cancer, 2002, 2(10): 795-803.
54. Kang YS, Park YG, Kim BK, et al. Angiotensin Ⅱ stimulates the synthesis of vascular endothelial growth factor through the p38 mitogen activated protein kinase pathway in cultured mouse podocytes. J Mol Endocrinol, 2006, 36(2): 377-388.
55. Matsuda M, Shimomura I. Increased oxidative stress in obesity: implications for metabolic syndrome, diabetes, hypertension, dyslipidemia, atherosclerosis, and cancer. Obes Res Clin Pract, 2013, 7(5): e330-e341.
56. Ishino K, Mutoh M, Totsuka Y, et al. Metabolic syndrome: a novel high-risk state for colorectal cancer. Cancer Lett, 2013, 334(1): 56-61.
57. 李师, 杜少辉. 原发性肝癌中医证型与脂代谢的分析. 广州: 广州中医药大学, 2018.
58. Li Z, Guan M, Lin Y, et al. Aberrant lipid metabolism in hepatocellular carcinoma revealed by liver lipidomics. Int J Mol Sci, 2017, 18(12): 2550.
59. Lu M, Hu XH, Li Q, et al. A specific cholesterol metabolic pathway is established in a subset of HCCs for tumor growth. J Mol Cell Biol, 2013, 5(6): 404-415.
60. Krautbauer S, Weiss TS, Wiest R, et al. Diagnostic value of systemic cholesteryl ester/free cholesterol ratio in hepatocellular carcinoma. Anticancer Res, 2017, 37(7): 3527-3535.
61. Kitahara CM, Berrington de González A, Freedman ND, et al. Total cholesterol and cancer risk in a large prospective study in Korea. J Clin Oncol, 2011, 29(12): 1592-1598.
62. 张俊国, 栾芳. 胆固醇在肝细胞肝癌分级和转移中作用的初步研究. 济南: 山东大学, 2016.
63. Mieno MN, Sawabe M, Tanaka N, et al. Significant association between hypolipoproteinemia(a) and lifetime risk of cancer: an autopsy study from a community-based Geriatric Hospital. Cancer Epidemiol, 2014, 38(5): 550-555.
64. Win AK, Macinnis RJ, Hopper JL, et al. Risk prediction models for colorectal cancer: a review. Cancer Epidemiol Biomarkers Prev, 2012, 21(3): 398-410.
65. Liu CS, Hsu HS, Li CI, et al. Central obesity and atherogenic dyslipidemia in metabolic syndrome are associated with increased risk for colorectal adenoma in a Chinese population. BMC Gastroenterol, 2010, 10: 51.
66. Liu X, Liang Y, Song R, Yang G, et al. Long non-coding RNA NEAT1-modulated abnormal lipolysis via ATGL drives hepatocellular carcinoma proliferation. Mol Cancer, 2018, 17(1): 90.
67. Che L, Chi W, Qiao Y, et al. Cholesterol biosynthesis supports the growth of hepatocarcinoma lesions depleted of fatty acid synthase in mice and humans. Gut, 2020, 69(1): 177-186.
68. 郭佩, 胡玉琳. 代谢综合征与原发性肝细胞癌的相关性研究. 长春: 吉林大学, 2017.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Research progress on relationship between metabolic syndrome and hepatocellular carcinoma and its mechanism

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