ERCC 1在前列腺癌PC-3细胞和组织样本中的表达及其临床意义

doi:10.3877/cma.j.issn.1674-3253.2022.02.015

中华腔镜泌尿外科杂志(电子版) ›› 2022, Vol. 16 ›› Issue (02) : 162 -168. doi: 10.3877/cma.j.issn.1674-3253.2022.02.015

实验研究

ERCC 1在前列腺癌PC-3细胞和组织样本中的表达及其临床意义

李腾成¹, 肖楚天², 赖圣杰¹, 黄群雄¹, 黄展森³, 方友强¹, 吴杰英¹^,^†(

)

^1. 510630　广州，中山大学附属第三医院泌尿外科
^2. 510655　广州，中山大学附属第六医院泌尿外科
^3. 510630　广州，中山大学附属第三医院不育与性医学科

收稿日期:2021-07-21 出版日期:2022-04-01
通信作者: 吴杰英
基金资助:
广东省自然科学基金(2018A030313261); 广东省医学科学技术研究基金(A2018079)

ERCC 1 expression in prostate cancer PC-3 cells and tissue samples and its clinical significance

Tengcheng Li¹, Chutian Xiao², Shengjie Lai¹, Qunxiong Huang¹, Zhansen Huang³, Youqiang Fang¹, Jieying Wu¹^,^†()

^1. Department of Urology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
^2. Department of Urology, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou 510655, China
^3. Department of Infertility and Sexual Medicine, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China

Received:2021-07-21 Published:2022-04-01
Corresponding author: Jieying Wu

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引用本文：

李腾成, 肖楚天, 赖圣杰, 黄群雄, 黄展森, 方友强, 吴杰英. ERCC 1在前列腺癌PC-3细胞和组织样本中的表达及其临床意义[J]. 中华腔镜泌尿外科杂志(电子版), 2022, 16(02): 162-168.

Tengcheng Li, Chutian Xiao, Shengjie Lai, Qunxiong Huang, Zhansen Huang, Youqiang Fang, Jieying Wu. ERCC 1 expression in prostate cancer PC-3 cells and tissue samples and its clinical significance[J]. Chinese Journal of Endourology(Electronic Edition), 2022, 16(02): 162-168.

目的

探讨切除修复交叉互补基因1(ERCC 1)在前列腺癌（PCa）PC-3细胞和前列腺样本中的表达情况及与预后的关系。

方法

Western blot检测小干扰核糖核酸（siRNA）ERCC 1在转染PC-3细胞后ERCC 1蛋白的表达水平，MTT法检测细胞增殖活力，Transwell试验检测细胞迁移和侵袭能力。免疫组化（IHC）检测80例PCa组织及30例前列腺增生（BPH）组织中ERCC 1蛋白的表达水平，分析ERCC 1与PCa临床病理特征及其预后关系。

结果

siRNA ERCC 1质粒转染PC-3细胞后Western blot检测证实ERCC 1表达水平明显减低。Transwell试验结果显示siRNA干扰表达ERCC 1后PC-3细胞迁移和侵袭能力下降，差异有统计学意义（P<0.05）。IHC结果提示ERCC 1在PCa样本中阳性表达率为71.3%（57/80），高表达率为23.8%（19/80，IRS≥6）；在BPH样本中阳性表达率为10%（3/30），均为低表达（IRS<6）。ERCC 1表达与PCa患者术前PSA值，Gleason评分，病理分期（pT），淋巴结转移和切缘阳性存在显著相关性（P<0.05），与年龄无显著相关性（P>0.05）。在PCa患者中ERCC 1低表达的无生化复发生存期（BRFS）显著长于ERCC 1高表达患者的BRFS（P<0.05）。单因素和多因素COX回归分析显示ERCC l高表达和病理分期（pT）均是PCa患者术后BRFS的独立危险因素。

结论

siRNA ERCC l抑制了PCa PC-3细胞的增殖生长、迁移和侵袭能力，ERCC 1在PCa样本中阳性表达率较高，并与低分化、高侵袭性特征的PCa相关。ERCC 1高表达可能是PCa患者预后独立危险因素之一。

关键词: 切除修复交叉互补基因1, 前列腺癌, 迁移, 侵袭, 预后

Objective

To investigate the expression level of excision repair cross complementary gene 1 (ERCC 1) in PC-3 cells and prostate samples and its relationship with prognosis.

Methods

After siRNA ERCC 1 was transfected into PC-3 cells, the expression level of ERCC 1 protein was detected by Western blot. The MTT method detected cell proliferation activity, andthe Transwell test detected cell migration and invasion capabilities. Immunohistochemistry (IHC) was used to detect the expression level of ERCC 1 protein in 80 PCa and 30 BPH samples, and its relationship with pathological characteristics and prognosis was analyzed.

Results

After siRNA ERCC 1 plasmid was transfected into PC-3 cells, Western blot showed that the expression level of ERCC 1 was significantly reduced. Transwell test showed that the migration and invasion ability of PC-3 cells after siRNA ERCC 1 expression was significantly decreased (P<0.05). IHC indicated that the positive expression rate of ERCC 1 in PCa samples was 71.3%(57/80), and the high expression rate was 23.8%(19/80; IRS≥6); the positive expression rate in BPH samples was 10% (3/30), all are low expression (IRS<6). The expression of ERCC 1 was significantly correlated with preoperative PSA value, Gleason score, pathological stage (pT), lymph node metastasis and positive margins in PCa patients (P<0.05), but not significantly correlated with age (P>0.05). In PCa patients, the biochemical relapse-free survival (BRFS) with low ERCC 1 expression was significantly longer than that of patients with high ERCC 1 expression (P<0.05). Univariate and multivariate COX regression analysis showed that high ERCC 1 expression and pT were independent risk factors with BRFS.

Conclusion

SiRNA ERCC 1 inhibit the proliferation, migration and invasion of PC-3 cells. The positive expression rate of ERCC 1 in PCa samples is higher, which related to poor differentiation and high invasive characteristics. The high expression of ERCC 1 may be one of the independent risk factors for the prognosis of PCa patients.

Key words: ERCC 1, Prostate cancer, Migration, Invasion, Prognosis

图1 转染ERCC 1质粒后ERCC 1表达水平(a)及PC-3细胞的活力(b)；Transwell迁移实验和侵袭实验(c和d)提示干扰　表达ERCC 1后PC-3细胞迁移和侵袭能力明显减弱。放大倍数100倍。^*P<0.05，t检验。注：NC为对照

图2 ERCC 1在BPH和PCa组织样本中表达的IHC代表图；免疫组化评分（IRS）=染色强度（负=0，弱=1，中度=2，强=3）×阳性染色细胞的百分比（0%=0，<10%=1，11-50%=2，51-80%=3，>80%=4）。IRS≥1为阳性表达，IRS<1为阴性表达；IRS≥6为高表达，IRS<6为低表达^[11]^***P<0.001

表1 ERCC 1表达与PCa临床病理资料特征的关系

项目		例数	ERCC 1(例)		χ²	P值
项目		例数	高表达	低表达	χ²	P值
病例		80	19	61
年龄(岁)
	<70	39	7	32
	≥70	41	12	28	1.570	0.210^*
术前tPSA(ng/ml)
	<10	40	3	37
	≥10	40	16	24	11.665	0.001^*
Gleason评分
	<7	40	4	36
	≥7	40	15	25	8.352	0.004^*
病理分期pT(例)
	<T3	49	5	44
	≥T3	31	14	17	12.813	<0.001^*
淋巴结转移(例)
	pN0/X	60	7	53
	pN1	20	12	8	19.350	<0.001^*
病理切缘(例)
	阳性	21	16	5
	阴性	59	3	56	43.240	<0.001^*
	生化复发(例)
	是	24	17	7
	否	56	2	54	41.971	<0.001^*

表1 ERCC 1表达与PCa临床病理资料特征的关系

项目		例数	ERCC 1(例)		χ²	P值
项目		例数	高表达	低表达	χ²	P值
病例		80	19	61
年龄(岁)
	<70	39	7	32
	≥70	41	12	28	1.570	0.210^*
术前tPSA(ng/ml)
	<10	40	3	37
	≥10	40	16	24	11.665	0.001^*
Gleason评分
	<7	40	4	36
	≥7	40	15	25	8.352	0.004^*
病理分期pT(例)
	<T3	49	5	44
	≥T3	31	14	17	12.813	<0.001^*
淋巴结转移(例)
	pN0/X	60	7	53
	pN1	20	12	8	19.350	<0.001^*
病理切缘(例)
	阳性	21	16	5
	阴性	59	3	56	43.240	<0.001^*
	生化复发(例)
	是	24	17	7
	否	56	2	54	41.971	<0.001^*

图3 ERCC 1表达量与无生化复发生存期的Kaplan-Meier曲线及Log-rank检验结果

表2 80例PCa患者预测预后单因素COX回归分析

项目	BRFS	P值
项目	HR(95%CI)	P值
年龄(<70 vs≥70岁)	1.431（0.515~3.796）	0.478^*
术前tPSA (<10 vs≥10 ng/ml)	0.398（0.084~1.884）	0.291^*
Gleason评分(<7 vs≥7分)	3.566（1.034~12.296）	0.021^*
病理分期(<T3 vs≥T3)	2.633（0.957~7.246）	0.043^*
淋巴结转移(否vs是)	1.931（0.753~4.948）	0.151^*
病理切缘(阴性vs阳性)	4.055（1.443~11.395）	0.003^*
ERCC 1 (低表达vs高表达)	5.699（1.822~17.824）	<0.001^***

表2 80例PCa患者预测预后单因素COX回归分析

项目	BRFS	P值
项目	HR(95%CI)	P值
年龄(<70 vs≥70岁)	1.431（0.515~3.796）	0.478^*
术前tPSA (<10 vs≥10 ng/ml)	0.398（0.084~1.884）	0.291^*
Gleason评分(<7 vs≥7分)	3.566（1.034~12.296）	0.021^*
病理分期(<T3 vs≥T3)	2.633（0.957~7.246）	0.043^*
淋巴结转移(否vs是)	1.931（0.753~4.948）	0.151^*
病理切缘(阴性vs阳性)	4.055（1.443~11.395）	0.003^*
ERCC 1 (低表达vs高表达)	5.699（1.822~17.824）	<0.001^***

表3 80例前列腺癌患者影响预后多因素COX回归分析

项目	BRFS	P值
项目	HR(95%CI)	P值
Gleason评分(<7 vs≥7分)	4.541（0.964~21.380）	0.056
病理分期(<T3 vs≥T3)	10.308（2.250~47.215）	0.003^*
病理切缘(阴性vs阳性)	1.112（0.360~3.431）	0.854
ERCC 1 (低表达vs高表达)	12.446（2.380~65.077）	0.003^*

表3 80例前列腺癌患者影响预后多因素COX回归分析

项目	BRFS	P值
项目	HR(95%CI)	P值
Gleason评分(<7 vs≥7分)	4.541（0.964~21.380）	0.056
病理分期(<T3 vs≥T3)	10.308（2.250~47.215）	0.003^*
病理切缘(阴性vs阳性)	1.112（0.360~3.431）	0.854
ERCC 1 (低表达vs高表达)	12.446（2.380~65.077）	0.003^*

[1]	Mohler JL, Antonarakis ES, Armstrong AJ, et al. Prostate Cancer, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology[J]. J Natl Compr Canc Netw, 2019, 17(5): 479-505.
[2]	Dellis A, Zagouri F, Liontos M, et al. Management of advanced prostate cancer_ A systematic review of existing guidelines and recommendations[J]. Cancer Treat Rev, 2019, 73: 54-61.
[3]	Ren Y, Shen C, Liu J, et al. Whole exome sequencing was used to identify novel mutations in recurrent prostate cancer and to construct a prediction model for recurrence of prostate cancer[J]. Chin J Exp Surg, 2019,36(10):1873-1878.
[4]	Leapman MS, Nguyen HG, Cowan JE, et al. Comparing prognostic utility of a single-marker immunohistochemistry approach with commercial gene expression profiling following radical prostatectomy[J]. Eur Urol, 2018, 74(5): 668-675.
[5]	Qian T, Zhang B, Qian C, et al. Association between common polymorphisms in ERCC. gene. and glioma risk: A meta-analysis of 15 studies[J]. Medicine (Baltimore), 2017, 96(20): e6832.
[6]	Klatte T, Seitz C, Rink M, et al. ERCC1 as a prognostic and predictive biomarker for urothelial carcinoma of the bladder following radical cystectomy[J]. J Uro, 2015, 194(5): 1456-1462.
[7]	孔蕾, 王俊杰, 王济东, 等. miR-503靶向ERCC1抑制食管鳞状细胞癌放疗抵抗作用的机制[J]. 中国肿瘤生物治疗杂志, 2019, 26(9): 969-975.
[8]	Chabanon RM, Muirhead G, Krastev DB, et al. PARP inhibition enhances tumor cell-intrinsic immunity in ERCC1-deficient non-small cell lung cancer[J]. J Clin Invest, 2019, 129(3): 1211-1228.
[9]	Buyyounouski MK, Choyke PL, Mckenney JK, et al. Prostate cancer - major changes. in. the American Joint Committee on Cancer eighth edition cancer staging manual[J]. CA Cancer J Clin, 2017, 67(3): 245-253.
[10]	Sanda MG, Cadeddu JA, Kirkby E, et al. Clinically Localized Prostate Cancer: AUA/ASTRO/SUO Guideline. Part I: Risk Stratification, Shared Decision Making, and Care Options[J]. J Uro, 2018, 199(3): 683-690.
[11]	Woythal N, Arsenic R, Kempkensteffen C, et al. Immunohistochemical validation of PSMA expression measured by 68Ga-PSMA PET/CT in primary prostate cancer[J]. J Nucl Med, 2018, 59(2): 238-243.
[12]	Yacoub A, Mckinstry R, Hinman D, et al. Epidermal growth factor and ionizing radiation up-regulate the DNA repair genes XRCC1 and ERCC1 in DU145 and LNCaP prostate carcinoma through MAPK signaling[J]. Radiat Res, 2003, 159(4): 439-452.
[13]	Li B, Shi X, Yuan Y, et al. ERCC1 rs11615 polymorphism increases susceptibility to breast. cancer: a meta-analysis of 4547 individuals[J]. Biosci Rep, 2018, 38(3): 87.
[14]	Yamda Y, Boku N, Nishina T, et al. Impact of excision repair cross-complementing gene 1. (ERCC1) on the outcomes of patients with advanced gastric cancer: correlative study in Japan Clinical Oncology Group Trial JCOG9912[J]. Ann Oncol, 2013, 24(10): 2560-2565.
[15]	Maithel SK, Coban I, Kneuertz PJ, et al. Differential expression of ERCC1 in pancreas adenocarcinoma: high tumor expression is associated with earlier recurrence and shortened survival after resection[J]. Ann Surg Oncol, 2011, 18(9): 2699-2705.
[16]	Greathouse KL, White JR, Vargas AJ, et al. Interaction between the microbiome and TP53. in. human lung cancer[J]. Genome Bio, 2018, 19(1): 123-16.
[17]	Gupta D, Heinen CD. The mismatch repair-dependent DNA damage response: Mechanisms. and. implications[J]. DNA repair(Amst), 2019, 78: 60-69.
[18]	Sabatella M, Pines A, Slyskova J, et al. ERCC1-XPF targeting to psoralen-DNA crosslinks depends on XPA and FANCD2[J]. Cell Mol Life Sci, 2019, 86: 811-812.
[19]	Gaillard H, Garcia-muse T, Aguilera A. Replication stress and cancer[J]. Nat Rev Cancer, 2015, 15(5): 276-289.
[20]	Jacobsen F, Taskin B, Melling N, et al. Increased ERCC1 expression is linked to. chromosomal. aberrations and adverse tumor biology in prostate cancer[J]. BMC Cancer, 2017, 17(1): 504-511.
[21]	Sagter G, Steurer S, Clauditz TS, et al. Clinical utility of quantitative gleason grading in. prostate biopsies and prostatectomy specimens[J]. Eur Urol, 2016, 69(4): 592-598.

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