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

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

Abstract

Abstract:

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

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.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhqjmnmwkzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.1674-3253.2022.02.015

https://zhqjmnmwkzz.cma-cmc.com.cn/EN/Y2022/V16/I02/162

Figures/Tables 6

References 21

[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.

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^*

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^*

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^***

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^***

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^*

Please choose a citation manager

Content to export