Clinical significance of apolipoprotein F in prognosis of patients with hepatocellular carcinoma

doi:10.3877/cma.j.issn.2095-3232.2018.01.018

Abstract

Abstract:

Objective

To investigate the expression of apolipoprotein (Apo) F in hepatocellular carcinoma (HCC) and its application value in the prognosis of patients with HCC.

Methods

50 HCC samples were procured from patients undergoing surgical resection in the Third Affiliated Hospital of Sun Yat-sen University between September 2015 and September 2016, and all the samples were confirmed by postoperative pathological examination. The informed consents of all patients were obtained and the local ethical committee approval was received. There were 37 males and 13 females, aged from 31-67 with a median age of 53 years old. The expression of ApoF mRNA in HCC tissues was detected by RT-PCR. The expression profile was analyzed by using data from the Gene Expression Omnibus (GEO). The expression of ApoF between two groups were compared by t test. Correlation analysis of clinical related parameter was conducted by Chi-square test, and survival prognosis was analyzed by Kaplan-Meier test and Log rank test.

Results

The average relative expression of ApoF mRNA in HCC tissues was 0.15±0.07, significantly lower than 0.55±0.09 in the adjacent tissues (t=-6.26, P<0.05). GEO online analysis showed that expression of ApoF was significantly correlated with the status of liver cirrhosis, and most HCC patients with liver cirrhosis presented low expression of ApoF (χ²=4.626, P<0.05). The 5-year disease-free survival was respectively 55.9% and 32.0% in ApoF high expression group and low expression group, where significant difference was observed (χ²=3.939, P<0.05).

Conclusions

Low expression of ApoF exists in HCC tissues, and it is related to the liver cirrhosis status of patients. Patients with low ApoF expression present poorer prognosis. ApoF plays a role in inhibiting the cancer.

Key words: Carcinoma, hepatocellular, Apolipoproteins, Prognosis

Boxuan Zhou, Zhicheng Yao, Zhiyong Xiong, Ruixi Li, Tianxing Dai, Mingxing Xu, Weiming Fan, Zheng Zhou, Hao Liang, Meihai Deng, Yunbiao Ling. Clinical significance of apolipoprotein F in prognosis of patients with hepatocellular carcinoma[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2018, 07(01): 73-76.

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References 19

[1]	Forner A, Llovet JM, Bruix J. Hepatocellular carcinoma[J]. Lancet, 2012, 379(9822):1245-1255.
[2]	Pogribny IP, Rusyn I. Role of epigenetic aberrations in the development and progression of human hepatocellular carcinoma[J]. Cancer Lett, 2014, 342(2):223-230.
[3]	Muir K, Hazim A, He Y, et al. Proteomic and lipidomic signatures of lipid metabolism in NASH-associated hepatocellular carcinoma[J]. Cancer Res, 2013, 73(15):4722-4731.
[4]	Yamashita T, Honda M, Takatori H, et al. Activation of lipogenic pathway correlates with cell proliferation and poor prognosis in hepatocellular carcinoma[J]. J Hepatol, 2009, 50(1):100-110.
[5]	Lagor WR, Fields DW, Khetarpal SA, et al. The effects of apolipoprotein F deficiency on high density lipoprotein cholesterol metabolism in mice[J]. PLoS One, 2012, 7(2):e31616.
[6]	Lagor WR, Brown RJ, Toh SA, et al. Overexpression of apolipoprotein F reduces HDL cholesterol levels in vivo[J]. Arterioscler Thromb Vasc Biol, 2009, 29(1):40-46.
[7]	Shen XB, Huang L, Zhang SH, et al. Transcriptional regulation of the apolipoprotein F (ApoF) gene by ETS and C/EBPα in hepatoma cells[J]. Biochimie, 2015(112):1-9.
[8]	Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation[J]. Science, 2009, 324(5930):1029-1033.
[9]	DeBerardinis RJ, Lum JJ, Hatzivassiliou G, et al. The biology of cancer: metabolic reprogramming fuels cell growth and proliferation[J]. Cell Metab, 2008, 7(1):11-20.
[10]	Cairns RA, Harris IS, Mak TW. Regulation of cancer cell metabolism[J]. Nat Rev Cancer, 2011, 11(2):85-95.
[11]	Kim J, DeBerardinis RJ. Blocking fatty acid synthesis reduces lung tumor growth in mice[J]. Nat Med, 2016, 22(10):1077-1078.
[12]	Rysman E, Brusselmans K, Scheys K, et al. De novo lipogenesis protects cancer cells from free radicals and chemotherapeutics by promoting membrane lipid saturation[J]. Cancer Res, 2010, 70(20):8117-8126.
[13]	Jiang J, Zhang X, Wu C, et al. Increased plasma apoM levels in the patients suffered from hepatocellular carcinoma and other chronic liver diseases[J]. Lipids Health Dis, 2008(7):25.
[14]	Yokoyama Y, Kuramitsu Y, Takashima M, et al. Protein level of apolipoprotein E increased in human hepatocellular carcinoma[J]. Int J Oncol, 2006, 28(3):625-631.
[15]	Ma XL, Gao XH, Gong ZJ, et al. Apolipoprotein A1: a novel serum biomarker for predicting the prognosis of hepatocellular carcinoma after curative resection[J]. Oncotarget, 2016, 7(43):70654-70668.
[16]	Shi J, Yang H, Duan X, et al. Apolipoproteins as differentiating and predictive markers for assessing clinical outcomes in patients with small cell lung cancer[J]. Yonsei Med J, 2016, 57(3):549-556.
[17]	Morton RE, Greene DJ. Conversion of lipid transfer inhibitor protein (apolipoprotein F) to its active form depends on LDL composition[J]. J Lipid Res, 2011, 52(12):2262-2271.
[18]	Peloso GM, Demissie S, Collins D, et al. Common genetic variation in multiple metabolic pathways influences susceptibility to low HDL-cholesterol and coronary heart disease[J]. J Lipid Res, 2010, 51(12):3524-3532.
[19]	He Y, Greene DJ, Kinter M, et al. Control of cholesteryl ester transfer protein activity by sequestration of lipid transfer inhibitor protein in an inactive complex[J]. J Lipid Res, 2008, 49(7):1529-1537.

参数		例数	高表达	低表达	χ²值	P值
年龄（岁）		?	?	?	1.918	0.166
?	≤55	166	78	88	?	?
?	>55	76	43	33	?	?
性别		?	?	?	0.353	0.553
?	男	213	105	108	?	?
?	女	29	16	13	?	?
ALT（U/L）		?	?	?	0.273	0.602
?	≤50	142	73	69	?	?
?	>50	100	48	52	?	?
AFP（μg/L）		?	?	?	0.410	0.522
?	≤200	128	67	61	?	?
?	>200	114	54	60	?	?
肝硬化		?	?	?	4.626	0.031
?	无	19	14	5	?	?
?	有	223	107	116	?	?
肿瘤直径（cm）		?	?	?	0.568	0.451
?	<5	153	74	79	?	?
?	≥5	89	47	42	?	?
肿瘤数目		?	?	?	0.098	0.754
?	单个	190	96	94	?	?
?	多发	52	25	27	?	?
AJCC T分期		?	?	?	0.595	0.743
?	T1	96	45	51	?	?
?	T2	78	41	37	?	?
?	T3	68	35	33	?	?
BCLC分期		?	?	?	2.102	0.552
?	0	37	22	15	?	?
?	A	152	74	78	?	?
?	B	24	11	13	?	?
?	C	29	14	15	?	?
CLIP分期		?	?	?	2.548	0.280
?	0	98	54	44	?	?
?	1	79	34	45	?	?
?	2,3,4,5	65	33	32	?	?
PRMS分级		?	?	?	2.000	0.157
?	高	121	66	55	?	?
?	低	121	55	66	?	?

参数		例数	高表达	低表达	χ²值	P值
年龄（岁）		?	?	?	1.918	0.166
?	≤55	166	78	88	?	?
?	>55	76	43	33	?	?
性别		?	?	?	0.353	0.553
?	男	213	105	108	?	?
?	女	29	16	13	?	?
ALT（U/L）		?	?	?	0.273	0.602
?	≤50	142	73	69	?	?
?	>50	100	48	52	?	?
AFP（μg/L）		?	?	?	0.410	0.522
?	≤200	128	67	61	?	?
?	>200	114	54	60	?	?
肝硬化		?	?	?	4.626	0.031
?	无	19	14	5	?	?
?	有	223	107	116	?	?
肿瘤直径（cm）		?	?	?	0.568	0.451
?	<5	153	74	79	?	?
?	≥5	89	47	42	?	?
肿瘤数目		?	?	?	0.098	0.754
?	单个	190	96	94	?	?
?	多发	52	25	27	?	?
AJCC T分期		?	?	?	0.595	0.743
?	T1	96	45	51	?	?
?	T2	78	41	37	?	?
?	T3	68	35	33	?	?
BCLC分期		?	?	?	2.102	0.552
?	0	37	22	15	?	?
?	A	152	74	78	?	?
?	B	24	11	13	?	?
?	C	29	14	15	?	?
CLIP分期		?	?	?	2.548	0.280
?	0	98	54	44	?	?
?	1	79	34	45	?	?
?	2,3,4,5	65	33	32	?	?
PRMS分级		?	?	?	2.000	0.157
?	高	121	66	55	?	?
?	低	121	55	66	?	?

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