Expressions of drug resistance gene proteins and Ki67 in primary liver cancer and their value in prognosis

doi:10.3877/cma.j.issn.2095-3232.2018.01.019

Abstract

Abstract:

Objective

To investigate the expressions of 4 drug resistance gene proteins P-glycoprotein (Pgp), Glutathionine-S-Transferase π (GST-π), topoisomerase Ⅱ (TopoⅡ) and thymidylate synthase (TS) and Ki67 in primary liver cancer (PLC) and their value in the prognosis of patients.

Methods

Samples were collected from 41 patients with PLC in the Third Affiliated Hospital of Nantong University between March 2008 and December 2016. The informed consents of all patients were obtained and the local ethical committee approval was received. There were 26 males and 15 females, with an average age of (56±10) years old. The expressions of Pgp, GST-π, Topo Ⅱ, TS and Ki67 in PLC tissues were detected by immunohistochemistry. Correlation analysis was conducted using Spearman correlation analysis. Survival rate was analyzed using Kaplan-Meier method and Log-rank test. Prognostic factors of these patients were analyzed by Cox proportional hazard regression model.

Results

Positive expressions of Pgp, GST-π, Topo Ⅱ, TS and Ki67 were detected in PLC tissues, and the positive expression rate was 73% (30/41), 7% (3/41), 61% (25/41), 39% (16/41) and 51% (21/41), respectively. The expression of TS was positively correlated with those of Pgp and Topo Ⅱ (r_s=0.484, 0.333; P<0.05). Survival analysis showed that there were significant differences in the survival between TS, Ki67 positive and negative patients (χ²=4.695, 5.784; P<0.05). Cox multivariate regression analysis showed that TS and Ki67 were the independent risk factors for the overall prognosis (HR=3.007, 17.108; P<0.05).

Conclusions

Expressions of Pgp, GST-π, Topo Ⅱ and TS can be detected in PLC. The expression of TS is positively correlated with those of Pgp and Topo Ⅱ. TS and Ki67 are the independent risk factors for the prognosis of patients.

Key words: Multidrug resistance-associated proteins, P-Glycoprotein, Glutathione S-transferase pi, DNA topoisomerases, Thymidylate synthase, Liver neoplasms, Prognosis, Risk factors

Feiyu Guo, Jun Yang, Shuming Xiong, Sen Gao, Maoqun Zhu, Jianping Li. Expressions of drug resistance gene proteins and Ki67 in primary liver cancer and their value in prognosis[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2018, 07(01): 77-81.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhgzwkssxdzzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.2095-3232.2018.01.019

https://zhgzwkssxdzzz.cma-cmc.com.cn/EN/Y2018/V07/I01/77

Figures/Tables 4

References 21

[1]	Zhu RX, Seto WK, Lai CL, et al. Epidemiology of hepatocellular carcinoma in the Asia-Pacific region[J]. Gut Liver, 2016, 10(3):332-339.
[2]	Tsurusaki M, Murakami T. Surgical and locoregional therapy of HCC: TACE[J]. Liver Cancer, 2015, 4(3):165-175.
[3]	Le Grazie M, Biagini MR, Tarocchi M, et al. Chemotherapy for hepatocellular carcinoma: the present and the future[J]. World J Hepatol, 2017, 9(21):907-920.
[4]	Li W, Song M. Expression of multidrug resistance proteins in invasive ductal carcinoma of the breast[J]. Oncol Lett, 2014, 8(5):2103-2109.
[5]	Chen JS, Wu BB, Bao HL, et al. Relationship between CIP2A expression, and prognosis and MDR-related proteins in patients with advanced gastric cancer[J]. Int J Clin Exp Pathol, 2015, 8(11):15007-15012.
[6]	Falato C, Lorent J, Tani E, et al. Ki67 measured in metastatic tissue and prognosis in patients with advanced breast cancer[J]. Breast Cancer Res Treat, 2014, 147(2):407-414.
[7]	Liang SN, Huang YJ, Liu LL, et al. Study on the correlation between the expression of Ki67 and FasL and prognosis of cervical carcinoma[J]. Genet Mol Res, 2015, 14(3):8634-8639.
[8]	Ledwitch KV, Roberts AG. Cardiovascular ion channel inhibitor drug-drug interactions with P-glycoprotein[J]. AAPS J, 2017, 19(2):409-420.
[9]	张彩兰，刘斌，杨艳丽，等．多药耐药基因PgP、ToPo-Ⅱ、GST-π与Ki-67在肺癌中的表达及其临床病理学意义[J]．现代肿瘤医学，2013，21(1):81-84.
[10]	Tandia M, Mhiri A, Paule B, et al. Correlation between clinical response to sorafenib in hepatocellular carcinoma treatment and polymorphisms of P-glycoprotein (ABCB1) and of breast cancer resistance protein (ABCG2): monocentric study[J]. Cancer Chemother Pharmacol, 2017, 79(4):759-766.
[11]	Marchewka Z, Piwowar A, Ruzik S, et al. Glutathione S- transferases class Pi and Mi and their significance in oncology[J]. Postepy Hig Med Dosw, 2017, 71(10):541-550.
[12]	Grassilli E, Narloch R, Federzoni E, et al. Inhibition of GSK3B bypass drug resistance of p53-null colon carcinomas by enabling necroptosis in response to chemotherapy[J]. Clin Cancer Res, 2013, 19(14):3820-3831.
[13]	林慧梅，安玉芳，张凡．多耐药基因在乳腺癌组织中的表达及价值[J]．河北医学，2015(10):1588-1590.
[14]	Kozuki T, Chikamori K, Surleac MD, et al. Roles of the C-terminal domains of topoisomerase Ⅱ α and topoisomeraseⅡβ in regulation of the decatenation checkpoint[J]. Nucleic Acids Res, 2017, 45(10):5995-6010.
[15]	Wei C, Pan Q, Wu K, et al. Clinical characterization for proliferation and metastasis in advanced hepatocellular carcinoma patients[J]. Int J Clin Exp Pathol, 2015, 8(10):13429-13431.
[16]	马静，魏素菊，王俊艳，等．BRCA1、TopoⅡα、Bcl-2在三阴乳腺癌中的表达及对预后的影响[J]．中国老年学杂志，2014，34(7):1811-1813.
[17]	李铁灵，郭海峰，李华洋．三阴性年轻乳腺癌患者BRCA1、TopoⅡα、Bcl-2表达和预后的关系[J]．现代肿瘤医学，2016(2):231-233.
[18]	肖秀丽，郭晶晶，龙汉安，等．四种耐药基因蛋白及Ki-67在浸润性乳腺癌组织中表达的临床意义[J]．泸州医学院学报．2012，35(3):277-281.
[19]	Al-Hajeili M, Shields AF, Hwang JJ, et al. Molecular testing to optimize and personalize decision making in the management of colorectal cancer[J]. Oncology, 2017, 31(4):301-312.
[20]	刘明东，余宗阳，赵忠全，等．PD-L1、Ki67预测非小细胞肺癌术后进展的研究[J]．现代肿瘤医学，2017，25(6):885-889.
[21]	赵文龙，吕立志，齐兴峰，等．肝细胞肝癌CD147和Ki67表达的相关性及其临床意义[J]．华南国防医学杂志，2016(11):700-704.

统计值	TS和Pgp	TS和GST-π	TS和TopoⅡ	TS和Ki67
r_s值	0.484	0.159	0.333	-0.054
P值	0.001	0.32	0.034	-0.737

统计值	TS和Pgp	TS和GST-π	TS和TopoⅡ	TS和Ki67
r_s值	0.484	0.159	0.333	-0.054
P值	0.001	0.32	0.034	-0.737

参数	单因素分析			多因素分析
参数	HR	95％CI	P值	HR	95％CI	P值
PgP	1.639	0.941～2.853	0.081	?	?	?
GST-π	1.325	0.723～2.427	0.362	?	?	?
TopoⅡ	1.943	1.026～3.678	0.041	1.143	0.428～3.054	0.789
TS	1.883	-1.056～-3.358	0.032	3.007	1.501～6.022	0.002
Ki67	5.890	-1.177～29.482	0.031	17.108	０2.576～113.608	0.003

参数	单因素分析			多因素分析
参数	HR	95％CI	P值	HR	95％CI	P值
PgP	1.639	0.941～2.853	0.081	?	?	?
GST-π	1.325	0.723～2.427	0.362	?	?	?
TopoⅡ	1.943	1.026～3.678	0.041	1.143	0.428～3.054	0.789
TS	1.883	-1.056～-3.358	0.032	3.007	1.501～6.022	0.002
Ki67	5.890	-1.177～29.482	0.031	17.108	０2.576～113.608	0.003

Please choose a citation manager

Content to export