MRI联合血清LRG1、LOXL2对前列腺癌的诊断价值

doi:10.3760/cma.j.cn371439-20250123-00119

摘要/Abstract

摘要：

目的探究MRI联合血清富含亮氨酸α2糖蛋白1（LRG1）、赖氨酰氧化酶样蛋白2（LOXL2）水平对前列腺癌的诊断价值。方法选取2021年1月至2023年12月于中国人民解放军联勤保障部队第九〇〇医院就诊的84例前列腺癌患者为研究对象（前列腺癌组），同时选取同期59例经病理确诊为前列腺良性病变的患者作为对照组。所有受试者均行多参数MRI检查。采用酶联免疫吸附法（ELISA）测定两组患者血清LRG1、LOXL2水平。采用受试者操作特征（ROC）曲线分析MRI，血清LRG1、LOXL2、前列腺癌特异性抗原（PSA）水平对前列腺癌的诊断价值。结果对照组与前列腺癌组患者的容量转移常数（K^trans）分别为（0.09±0.03）、（0.13±0.04）/min，速率常数（K_ep）分别为（0.48±0.11）、（0.53±0.12）/min，表观扩散系数（ADC）分别为（1.16±0.15）×10^-3、（0.92±0.13）×10^-3mm²/s，差异均有统计学意义（t=6.50，P<0.001；t=2.54，P=0.012；t=10.20，P<0.001）。前列腺癌组与对照组患者血清LRG1水平分别为（115.48±15.61）、（92.51±14.34）ng/ml，LOXL2水平分别为（6.79±1.15）、（5.21±0.93）ng/ml，PSA水平分别为16.05（12.23，22.89）、6.04（2.62，12.04）ng/ml，差异均有统计学意义（t=8.96，P<0.001；t=8.73，P<0.001；Z=7.02，P<0.001）。ROC曲线分析显示，MRI及血清LRG1、LOXL2、PSA水平诊断前列腺癌的曲线下面积（AUC）分别为0.826、0.844、0.829、0.845，MRI及血清LRG1、LOXL2水平三者联合诊断前列腺癌的AUC为0.929，联合诊断效能优于MRI（Z=4.51，P<0.001），血清LRG1（Z=3.65，P<0.001）、LOXL2（Z=3.91，P<0.001）、PSA（Z=2.30，P=0.022）单独诊断。结论 MRI联合血清LRG1、LOXL2水平具有较高的前列腺癌诊断效能。

关键词: 前列腺肿瘤, MRI, 诊断, 富含亮氨酸α2糖蛋白1, 赖氨酰氧化酶样蛋白2

Abstract:

Objective To explore the diagnostic value of MRI combined with serum levels of leucine-rich α2 glycoprotein 1 （LRG1） and lysyl oxidase like-2 protein （LOXL2） for prostate cancer. Methods A total of 84 patients with prostate cancer who were treated at the 900th Hospital of PLA Joint Logistic Support Force from January 2021 to December 2023 were selected as the research subjects （prostate cancer group）. Meanwhile， 59 patients diagnosed with benign prostate lesions by pathology during the same period were selected as the control group. All subjects underwent multiparametric MRI examination. The levels of serum LRG1 and LOXL2 in the two groups of patients were determined by enzyme linked immunosorbent assay （ELISA）. Receiver operator characteristic （ROC） curve was used to analyze the diagnostic value of MRI， levels of serum LRG1， LOXL2 and prostate specific antigen （PSA） for prostate cancer. Results The volume transfer constant （K^trans） of the control group and the prostate cancer group were （0.09±0.03） and （0.13±0.04）/min， respectively， the rate constant （K_ep） were （0.48±0.11） and （0.53±0.12）/min， respectively， and the apparent diffusion coefficient （ADC） were （1.16±0.15）×10^-3 and （0.92±0.13）×10^-3mm²/s， respectively， with statistically significant differences （t=6.50， P<0.001； t=2.54， P=0.012； t=10.20， P<0.001）. The serum LRG1 levels of the prostate cancer group and the control group were （115.48±15.61） and （92.51±14.34） ng/ml， respectively， the LOXL2 levels were （6.79±1.15） and （5.21±0.93） ng/ml， respectively， and the PSA levels were 16.05 （12.23， 22.89） and 6.04 （2.62， 12.04） ng/ml， respectively， with statistically significant differences （t=8.96，P<0.001； t=8.73， P<0.001； Z=7.02， P<0.001）. ROC curve analysis showed that， the area under the curve （AUC） of MRI， serum LRG1， LOXL2 and PSA levels in the diagnosis of prostate cancer were 0.826， 0.844， 0.829， and 0.845， respectively. The AUC of the combined diagnosis of prostate cancer by MRI， serum levels of LRG1 and LOXL2 was 0.929， and the combined diagnostic efficacy was better than that of MRI （Z=4.51， P<0.001）， serum LRG1 （Z=3.65， P<0.001）， LOXL2 （Z=3.91， P<0.001）， and PSA （Z=2.30， P=0.022） alone. Conclusions MRI combined with the levels of serum LRG1 and LOXL2 has a relatively high diagnostic efficacy for prostate cancer.

Key words: Prostatic neoplasms, MRI, Diagnosis, Leucine-rich α2 glycoprotein 1, Lysyl oxidase like-2 protein

叶蕊, 陈振, 郝宁宁, 李溶溶. MRI联合血清LRG1、LOXL2对前列腺癌的诊断价值[J]. 国际肿瘤学杂志, 2025, 52(11): 695-699.

Ye Rui, Chen Zhen, Hao Ningning, Li Rongrong. Diagnostic value of MRI combined with serum LRG1 and LOXL2 for prostate cancer[J]. Journal of International Oncology, 2025, 52(11): 695-699.

图/表 5

表1

表2

表3

表4

图1

参考文献 22

[1]	Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2024, 74(3): 229-263. DOI: 10.3322/caac.21834.
[2]	Okubo Y, Sato S, Terao H, et al. Review of the developing landscape of prostate biopsy and its roles in prostate cancer diagnosis and treatment[J]. Arch Esp Urol, 2023, 76(9): 633-642. DOI: 10.56434/j.arch.esp.urol.20237609.78.
[3]	Sekhoacha M, Riet K, Motloung P, et al. Prostate cancer review: genetics, diagnosis, treatment options, and alternative approaches[J]. Molecules, 2022, 27(17): 5730. DOI: 10.3390/molecules27175730.
[4]	Camilli C, Hoeh AE, De Rossi G, et al. LRG1: an emerging player in disease pathogenesis[J]. J Biomed Sci, 2022, 29(1): 6. DOI: 10.1186/s12929-022-00790-6. pmid: 35062948
[5]	Liu P, Wang W, Wang F, et al. Alterations of plasma exosomal proteins and motabolies are associated with the progression of castration-resistant prostate cancer[J]. J Transl Med, 2023, 21(1): 40. DOI: 10.1186/s12967-022-03860-3. pmid: 36681849
[6]	Alonso-Nocelo M, Ruiz-Cañas L, Sancho P, et al. Macrophages direct cancer cells through a LOXL2-mediated metastatic cascade in pancreatic ductal adenocarcinoma[J]. Gut, 2023, 72(2): 345-359. DOI: 10.1136/gutjnl-2021-325564.
[7]	Ma S, Xu M, Zhang J, et al. Analysis and functional validations of multiple cell death patterns for prognosis in prostate cancer[J]. Int Immunopharmacol, 2024, 143(Part 1): 113216. DOI: 10.1016/j.intimp.2024.113216.
[8]	赫捷, 陈万青, 李霓, 等. 中国前列腺癌筛查与早诊早治指南(2022, 北京)[J]. 中国肿瘤, 2022, 31(1): 1-30. DOI: 10.11735/j.issn.1004-0242.2022.01.A001.
[9]	Turkbey B, Rosenkrantz AB, Haider MA, et al. Prostate imaging reporting and data system version 2.1: 2019 update of prostate imaging reporting and data system version 2[J]. Eur Urol, 2019, 76(3): 340-351. DOI: 10.1016/j.eururo.2019.02.033. pmid: 30898406
[10]	Fernandes MC, Yildirim O, Woo S, et al. The role of MRI in prostate cancer: current and future directions[J]. MAGMA, 2022, 35(4): 503-521. DOI: 10.1007/s10334-022-01006-6. pmid: 35294642
[11]	赵鑫, 范学武, 田龙, 等. 三维超声在前列腺癌图像引导放疗中的应用与评价研究[J]. 国际肿瘤学杂志, 2024, 51(1): 43-49. DOI: 10.3760/cma.j.cn371439-20230418-00005.
[12]	Wu H, Zeng C, Wu G, et al. Exosomal LRG1 promotes non-small cell lung cancer proliferation and metastasis by binding FN1 protein[J]. Exp Cell Res, 2024, 439(2): 114097-114105. DOI: 10.1016/j.yexcr.2024.114097.
[13]	Zhao X, Chen J, Zhang C, et al. LncRNA AGAP2-AS1 interacts with IGF2BP2 to promote bladder cancer progression via regulating LRG1 mRNA stability[J]. Cell Signal, 2023, 111: 110839. DOI: 10.1016/j.cellsig.2023.110839.
[14]	He L, Feng A, Guo H, et al. LRG1 mediated by ATF3 promotes growth and angiogenesis of gastric cancer by regulating the SRC/STAT3/VEGFA pathway[J]. Gastric Cancer, 2022, 25(3): 527-541. DOI: 10.1007/s10120-022-01279-9. pmid: 35094168
[15]	Dritsoula A, Camilli C, Moss SE, et al. The disruptive role of LRG1 on the vasculature and perivascular microenvironment[J]. Front Cardiovasc Med, 2024, 11: 1386177. DOI: 10.3389/fcvm.2024.1386177.
[16]	Wu D, Xie W, Chen X, et al. LRG1 is involved in the progression of ovarian cancer via modulating FAK/AKT signaling pathway[J]. Front Biosci (Landmark Ed), 2023, 28(5): 101. DOI: 10.31083/j.fbl2805101. pmid: 37258465
[17]	Peng T, Lin S, Meng Y, et al. LOXL2 small molecule inhibitor restrains malignant transformation of cervical cancer cells by repres-sing LOXL2-induced epithelial-mesenchymal transition (EMT)[J]. Cell Cycle, 2022, 21(17): 1827-1841. DOI: 10.1080/15384101.2022.2073047.
[18]	Shen Y, Yan J, Li L, et al. LOXL2-induced PEAR1 Ser891 phosphorylation suppresses CD44 degradation and promotes triple-negative breast cancer metastasis[J]. J Clin Invest, 2024, 134(16): e177357-e177373. DOI: 10.1172/JCI177357.
[19]	Pascual-Reguant L, Serra-Camprubí Q, Datta D, et al. Interactions between BRD4S, LOXL2, and MED1 drive cell cycle transcription in triple-negative breast cancer[J]. EMBO Mol Med, 2023, 15(12): e18459. DOI: 10.15252/emmm.202318459.
[20]	Xia Q, Du Z, Chen M, et al. A protein complex of LCN2, LOXL2 and MMP9 facilitates tumour metastasis in oesophageal cancer[J]. Mol Oncol, 2023, 17(11): 2451-2471. DOI: 10.1002/1878-0261.13529.
[21]	罗瑛译, 韦利娥, 玉开温. 多模态MRI参数联合血清miR-301a水平评估前列腺癌危险程度及预测早期复发的价值[J]. 放射学实践, 2022, 37(5): 560-565. DOI: 10.13609/j.cnki.1000-0313.2022.05.005.
[22]	许品, 李锋, 张双, 等. 磁共振成像联合血清microRNA-221对前列腺癌的诊断价值[J]. 中国现代医学杂志, 2023, 33(18): 26-30. DOI: 10.3969/j.issn.1005-8982.2023.18.005.

序列	重复时间（ms）	回波时间（ms）	层厚（mm）	层间距（mm）	扫描野（cm×cm）
T1WI	700	7	4	1	20×20
T2WI	4 100	80	4	1	25×25
DWI	6 000	80	4	1	20×20
DCE	5	1.7	3.5	0.35	26×26

项目	对照组（n=59）	前列腺癌组（n=84）	t/χ²值	P值
年龄（岁）	65.85±4.26	66.37±4.29	0.72	0.475
BMI（kg/m²）	23.19±2.10	23.56±2.05	1.05	0.295
糖尿病	12（20.34）	28（33.33）	2.91	0.088
高血压	15（25.42）	34（40.48）	3.49	0.062
高脂血症	3（5.08）	10（11.90）	1.95	0.163
慢性肾脏病	5（8.47）	15（17.86）	2.54	0.111
前列腺癌家族史	3（5.08）	11（13.10）	2.52	0.113
K^trans（/min）	0.09±0.03	0.13±0.04	6.50	<0.001
K_ep（/min）	0.48±0.11	0.53±0.12	2.54	0.012
ADC（×10^-3 mm²/s）	1.16±0.15	0.92±0.13	10.20	<0.001

指标	截断值（ng/ml）	AUC	95%CI	敏感性	特异性	约登指数
MRI		0.826	0.753~0.899	0.821	0.831	0.652
LRG1	103.20	0.844	0.782~0.907	0.762	0.780	0.542
LOXL2	5.78	0.829	0.762~0.895	0.810	0.678	0.487
PSA	7.65	0.845	0.815~0.934	0.857	0.695	0.552
MRI+PSA		0.916	0.868~0.965	0.893	0.814	0.706
MRI+LRG1+LOXL2		0.929	0.888~0.971	0.917	0.831	0.747