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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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

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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.	任會娜, 黃文祥. 代謝綜合征與肝臟相關事件的關系—系統回顧與meta分析. 重慶: 重慶醫科大學, 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.	中華醫學會糖尿病學分會. 中國 2 型糖尿病防治指南(2017 年版). 中華糖尿病雜志, 2018, 10(1): 4-67.
7.	梁曉峰, 李利娟, 劉俊田. 代謝綜合征與胃癌發病風險及臨床病理特征相關性的研究. 中國腫瘤臨床, 2019, 46(19): 986-993.
8.	陳濤, 邢雪. 代謝綜合征與胰腺癌的發生、惡性程度及預后的關系研究. 大連: 大連醫科大學, 2018.
9.	楊小康, 徐光勇. 代謝綜合征與前列腺癌的相關性研究. 重慶: 重慶醫科大學, 2020.
10.	陳瑾歆, 陳建業. 代謝綜合征發病機制的研究進展. 川北醫學院學報, 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. 肥胖促進腫瘤發生發展的相關機制研究進展. 中國慢性病預防與控制, 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.	謝銳, 梁紅亮, 楊舒鈞, 等. 體質量指數與肝癌患者臨床病理特征及預后關系. 臨床軍醫雜志, 2020, 48(3): 347-348, 351.
16.	林偉寅, 侯金林, 孫劍. 超重和肥胖對慢性乙型肝炎患者肝臟炎癥及肝癌的影響. 廣州: 南方醫科大學, 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, 曹紅, 龐雪利, 等. 瘦素對人乳腺癌 MCF-7 細胞遷移和侵襲的影響及其機制. 細胞與分子免疫學雜志, 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, V?ls 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.	謝良地, 吳可貴, 許能鋒, 等. 高血壓病人發生腫瘤危險性的研究. 高血壓雜志, 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.	李師, 杜少輝. 原發性肝癌中醫證型與脂代謝的分析. 廣州: 廣州中醫藥大學, 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.	張俊國, 欒芳. 膽固醇在肝細胞肝癌分級和轉移中作用的初步研究. 濟南: 山東大學, 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. 代謝綜合征與原發性肝細胞癌的相關性研究. 長春: 吉林大學, 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. 任會娜, 黃文祥. 代謝綜合征與肝臟相關事件的關系—系統回顧與meta分析. 重慶: 重慶醫科大學, 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. 中華醫學會糖尿病學分會. 中國 2 型糖尿病防治指南(2017 年版). 中華糖尿病雜志, 2018, 10(1): 4-67.
7. 梁曉峰, 李利娟, 劉俊田. 代謝綜合征與胃癌發病風險及臨床病理特征相關性的研究. 中國腫瘤臨床, 2019, 46(19): 986-993.
8. 陳濤, 邢雪. 代謝綜合征與胰腺癌的發生、惡性程度及預后的關系研究. 大連: 大連醫科大學, 2018.
9. 楊小康, 徐光勇. 代謝綜合征與前列腺癌的相關性研究. 重慶: 重慶醫科大學, 2020.
10. 陳瑾歆, 陳建業. 代謝綜合征發病機制的研究進展. 川北醫學院學報, 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. 肥胖促進腫瘤發生發展的相關機制研究進展. 中國慢性病預防與控制, 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. 謝銳, 梁紅亮, 楊舒鈞, 等. 體質量指數與肝癌患者臨床病理特征及預后關系. 臨床軍醫雜志, 2020, 48(3): 347-348, 351.
16. 林偉寅, 侯金林, 孫劍. 超重和肥胖對慢性乙型肝炎患者肝臟炎癥及肝癌的影響. 廣州: 南方醫科大學, 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, 曹紅, 龐雪利, 等. 瘦素對人乳腺癌 MCF-7 細胞遷移和侵襲的影響及其機制. 細胞與分子免疫學雜志, 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, V?ls 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. 謝良地, 吳可貴, 許能鋒, 等. 高血壓病人發生腫瘤危險性的研究. 高血壓雜志, 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. 李師, 杜少輝. 原發性肝癌中醫證型與脂代謝的分析. 廣州: 廣州中醫藥大學, 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. 張俊國, 欒芳. 膽固醇在肝細胞肝癌分級和轉移中作用的初步研究. 濟南: 山東大學, 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.
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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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