Diagnostic value of serum lipocalin 2 combined with prostatespecific antigen in prostate cancer

doi:10.3760/cma.j.issn.1673-422X.2018.01.006

Abstract

Abstract: ObjectiveTo investigate the diagnostic value of lipocalin 2 (LCN2) combined with prostatespecific antigen (PSA) in prostate cancer (PCa). MethodsEnzymelinked immunosorbent assay (ELISA) was used to determine the levels of serum LCN2 in patients with PCa (PCa group, n=82), patients with benign prostatic hyperplasia (BPH group, n=40) and healthy subjects (NC group, n=30). The levels of serum PSA were measured by chemiluminescence. The diagnostic value of LCN2 combined with PSA in PCa was analyzed by the receiver operating characteristic (ROC) curve. The relationship between the level of LCN2 and clinical parameters in PCa patients was analyzed. ResultsThe levels of serum LCN2 in PCa group, BPH group and NC group were (88.97±40.83) pg/ml, (53.12±25.66) pg/ml, (13.34±4.86) pg/ml (F=61.306, P<0.001). The level of LCN2 in PCa group was significantly higher than that in BPH group and NC group (both P<0.001). The levels of serum PSA in PCa group, BPH group and NC group were (17.65±8.43) ng/ml, (11.27±3.56) ng/ml, (2.61±0.87) ng/ml (F=60.959, P<0.001). The level of serum PSA in PCa group was significantly higher than that in BPH group and NC group (both P<0.001). There was positive correlation between serum LCN2 and PSA levels (r=0.360, P＜0.001). The levels of serum LCN2 in PCa patients with different Gleason score, TNM stage and distant metastasis were significantly different (F=8.546, P＜0.001; t=3.421, P=0.001; t=3.622, P=0.010). The area under the curve (AUC) of serum LCN2 was 0.763 (95%CI: 0.6770.850, P＜0.001). The sensitivity and specificity of serum LCN2 were 62.2% and 85.0%. The AUC of PSA was 0.750 (95%CI: 0.6650.836, P＜0.001). The sensitivity and specificity of serum PSA were 51.2% and 87.5%. The AUC of LCN2 combined with PSA was 0.822 (95%CI: 0.7490.895, P＜0.001). ConclusionSerum LCN2 level in the patients with PCa is significantly higher, which participates in tumor invasion. LCN2 may be a potential serum marker for the diagnosis of PCa. Combined detection of LCN2 and PSA contributes to the early diagnosis of PCa.

Key words: Prostate neoplasms, Prostatespecific antigen, Lipocalin 2

Bi Sicheng*, Liu Hao, Zhang Peng, Li Zhe, Mai Tiejun, Zhu Zhizhen. Diagnostic value of serum lipocalin 2 combined with prostatespecific antigen in prostate cancer[J]. Journal of International Oncology, 2018, 45(1): 27-.

References

［1］ Siegel RL, Miller KD, Jemal A. Cancer statistics［J］. CA Cancer J Clin, 2016, 66(1): 730. DOI: 10.3322/caac.21332. ［2］ Aydn S, Boz MY. Rapid changes in the incidence of urinary system cancers in Turkey［J］. Turk J Urol, 2015, 41(4): 215220. DOI: 10.5152/tud.2015.45548. ［3］ Makarov DV, Loeb S, Magheli A, et al. Significance of preoperative PSA velocity in men with low serum PSA and normal DRE［J］. World J Urol, 2011, 29(1): 1114. DOI: 10.1007/s0034501006254. ［4］ Heidegger I, Klocker H, Steiner E, et al. ［2］ proPSA is an early marker for prostate cancer aggressiveness［J］. Prostate Cancer Prostatic Dis, 2014, 17(1): 7074. DOI: 10.1038/pcan.2013.50. ［5］ Harjes U. Cancer: ironing it out［J］. Nat Rev Drug Discov, 2017, 16(9): 602. DOI: 10.1038/nrd.2017.168. ［6］ Chakraborty S, Kaur S, Guha SA. The multifaceted roles of neutrophil gelatinase associated lipocalin (NGAL) in inflammation and cancer［J］. Biochim Biophys Acta, 2012, 1826(1): 129169. DOI: 10.1016/j.bbcan.2012.03.008. ［7］ GomezChou SB, SwidnickaSiergiejko AK, Badi N, et al. Lipocalin2 promotes pancreatic ductal adenocarcinoma by regulating inflammation in the tumor microenvironment［J］. Cancer Res, 2017, 77(10): 26472660. DOI: 10.1158/00085472.CAN161986. ［8］ Ricci S, Bruzzese D, Di Carlo A. Evaluation of MMP2, MMP9, TIMP1, TIMP2, NGAL and MMP9/NGAL complex in urine and sera from patients with bladder cancer［J］. Oncol Lett, 2015, 10(4): 25272532. DOI: 10.3892/ol.2015.3558. ［9］ Chiang KC, Yeh TS, Wu RC, et al. Lipocalin 2 (LCN2) is a promising target for cholangiocarcinoma treatment and bile LCN2 level is a potential cholangiocarcinoma diagnostic marker［J］. Sci Rep, 2016, 6: 36138. DOI: 10.1038/srep36138. ［10］ Abella V, Scotece M, Conde J, et al. The potential of lipocalin2/NGAL as biomarker for inflammatory and metabolic diseases［J］. Biomarkers, 2015, 20(8): 565571. DOI: 10.3109/1354750X.2015.1123354. ［11］ Rodvold JJ, Mahadevan NR, Zanetti M. Lipocalin 2 in cancer: when good immunity goes bad［J］. Cancer Lett, 2012, 316(2): 132138. DOI: 10.1016/j.canlet.2011.11.002. ［12］ Martí J, Fuster J, Solà AM, et al. Prognostic value of serum neutrophil gelatinaseassociated lipocalin in metastatic and nonmetastatic colorectal cancer［J］. World J Surg, 2013, 37(5): 11031109. DOI: 10.1007/s002680131930z. ［13］ Volpe V, Raia Z, Sanguigno L, et al. NGAL controls the metastatic potential of anaplastic thyroid carcinoma cells［J］. J Clin Endocrinol Metab, 2013, 98(1): 228235. DOI: 10.1210/jc.20122528. ［14］ Ding G, Fang J, Tong S, et al. Overexpression of lipocalin 2 promotes cell migration and invasion through activating ERK signaling to increase SLUG expression in prostate cancer［J］. Prostate, 2015, 75(9): 957968. DOI: 10.1002/pros.22978. ［15］ Ding G, Wang J, Feng C, et al. Lipocalin 2 overexpression facilitates progress of castrationresistant prostate cancer via improving androgen receptor transcriptional activity［J］. Oncotarget, 2016, 7(39): 6430964317. DOI: 10.18632/oncotarget.11790. ［16］ Mahadevan NR, Rodvold J, Almanza G, et al. ER stress drives Lipocalin 2 upregulation in prostate cancer cells in an NFκBdependent manner［J］. BMC Cancer, 2011, 11: 229. DOI: 10.1186/1471240711229. ［17］ Tung MC, Hsieh SC, Yang SF, et al. Knockdown of lipocalin2 suppresses the growth and invasion of prostate cancer cells［J］. Prostate, 2013, 73(12): 12811290. DOI: 10.1002/pros.22670. ［18］ Chappell WH, Abrams SL, Lertpiriyapong K, et al. Novel roles of androgen receptor, epidermal growth factor receptor, TP53, regulatory RNAs, NFkappaB, chromosomal translocations, neutrophil associated gelatinase, and matrix metalloproteinase9 in prostate cancer and prostate cancer stem cells［J］. Adv Biol Regul, 2016, 60: 6487. DOI: 10.1016/j.jbior.2015.10.001. ［19］ Kawahara R, Bollinger JG, Rivera C, et al. A targeted proteomic strategy for the measurement of oral cancer candidate biomarkers in human saliva［J］. Proteomics, 2016, 16(1): 159173. DOI: 10.1002/pmic.201500224.

[1]	Jin Ming, Zhen Shuqing, Wang Yanqiao, Shen Hongxia, Zhang Aimin, Hui Limei. Effects of propofol on malignant biological behaviors of prostate cancer DU145 cells and its mechanism [J]. Journal of International Oncology, 2022, 49(8): 453-458.
[2]	Zhang Yongli, Zhang Ruojia, Fan Huancai, Ge Luna, Wang Lin. TXNDC5-Prx2 axis regulates drug resistance of prostate cancer cells [J]. Journal of International Oncology, 2021, 48(8): 473-478.