Disease specific urinary biomarkers in the central nervous system

被引:2
作者
Duggins-Warf, Micah [1 ,2 ]
Ghalali, Aram [1 ,2 ]
Sesen, Julie [1 ,2 ]
Martinez, Tyra [1 ,2 ]
Fehnel, Katie P. [1 ,2 ]
Pineda, Steven [1 ,2 ]
Zurakowski, David [3 ]
Smith, Edward R. [1 ,2 ]
机构
[1] Boston Childrens Hosp, Vasc Biol Program, 300 Longwood Ave, Boston, MA 02115 USA
[2] Boston Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA
[3] Boston Childrens Hosp, Dept Surg, Boston, MA USA
关键词
ENDOTHELIAL GROWTH-FACTOR; CELL LUNG-CANCER; PROSTATE-CANCER; TUMOR-GROWTH; MATRIX METALLOPROTEINASES; TISSUE INHIBITOR; EXPRESSION; INVASION; MOYAMOYA; THROMBOSPONDIN-2;
D O I
10.1038/s41598-023-46763-z
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Urinary biomarkers can diagnose and monitor pathophysiologic conditions in the central nervous system (CNS). However, focus is often on single diseases, with limited data on discriminatory capability of this approach in a general setting. Here, we demonstrate that different classes of CNS disease exhibit distinct biomarker patterns, evidence of disease-specific "fingerprinting." Urine from 218 patients with pathology-confirmed tumors or cerebrovascular disease, controls (n = 33) were collected. ELISA and/or bead-based multiplexing quantified levels of 21 putative urinary biomarkers. Analysis identified biomarkers capable of distinguishing each disease from controls and other diseases. Mann-Whitney U tests identified biomarkers with differential expression between disease types and controls (P <= 0.001). Subsequent receiver-operating characteristic (ROC) analyses revealed distinguishing biomarkers with high sensitivity and specificity. Areas under the curve (AUCs) ranged 0.8563-1.000 (P values <= 0.0003), sensitivities ranged 80.00-100.00%, and specificities ranged 80.95-100.00%. These data demonstrate proof-of-principle evidence that disease-specific urinary biomarker signatures exist. In contrast to non-specific responses to ischemia or injury, these results suggest that urinary biomarkers accurately reflect unique biological processes distinct to different diseases. This work can be used to generate disease-specific panels for enhancing diagnosis, assisting less-invasive follow-up and herald utility by revealing putative disease-specific therapeutic targets.
引用
收藏
页数:11
相关论文
共 68 条
[1]   Netrin-1 Promotes Medulloblastoma Cell Invasiveness and Angiogenesis, and Demonstrates Elevated Expression in Tumor Tissue and Urine of Patients with Pediatric Medulloblastoma [J].
Akino, Tomoshige ;
Han, Xuezhe ;
Nakayama, Hironao ;
McNeish, Brendan ;
Zurakowski, David ;
Mammoto, Akiko ;
Klagsbrun, Michael ;
Smith, Edward .
CANCER RESEARCH, 2014, 74 (14) :3716-3726
[2]   A review of tissue inhibitor of metalloproteinases-3 (TIMP-3) and experimental analysis of its effect on primary tumor growth [J].
AnandApte, B ;
Bao, L ;
Smith, R ;
Iwata, K ;
Olsen, BR ;
Zetter, B ;
Apte, SS .
BIOCHEMISTRY AND CELL BIOLOGY-BIOCHIMIE ET BIOLOGIE CELLULAIRE, 1996, 74 (06) :853-862
[3]   A phase I/II study of veliparib (ABT-888) with radiation and temozolomide in newly diagnosed diffuse pontine glioma: a Pediatric Brain Tumor Consortium study [J].
Baxter, Patricia A. ;
Su, Jack M. ;
Onar-Thomas, Arzu ;
Billups, Catherine A. ;
Li, Xiao-Nan ;
Poussaint, Tina Young ;
Smith, Edward R. ;
Thompson, Patrick ;
Adesina, Adekunle ;
Ansell, Pete ;
Giranda, Vincent ;
Paulino, Arnold ;
Kilburn, Lindsey ;
Quaddoumi, Ibrahim ;
Broniscer, Alberto ;
Blaney, Susan M. ;
Dunkel, Ira J. ;
Fouladi, Maryam .
NEURO-ONCOLOGY, 2020, 22 (06) :875-885
[4]   TNF-α promotes invasive growth through the MET signaling pathway [J].
Bigatto, Viola ;
De Bacco, Francesca ;
Casanova, Elena ;
Reato, Gigliola ;
Lanzetti, Letizia ;
Isella, Claudio ;
Sarotto, Nana ;
Comoglio, Paolo M. ;
Boccaccio, Carla .
MOLECULAR ONCOLOGY, 2015, 9 (02) :377-388
[5]   High circulating hepatocyte growth factor levels associate with epithelial to mesenchymal transition and poor outcome in small cell lung cancer patients [J].
Canadas, Israel ;
Taus, Alvaro ;
Gonzalez, Iria ;
Villanueva, Xavier ;
Gimeno, Javier ;
Pijuan, Lara ;
Domine, Manuel ;
Sanchez-Font, Albert ;
Vollmer, Ivan ;
Menendez, Silvia ;
Arpi, Oriol ;
Mojal, Sergi ;
Rojo, Federico ;
Rovira, Ana ;
Albanell, Joan ;
Arriola, Edurne .
ONCOTARGET, 2014, 5 (14) :5246-5256
[6]   Down-regulation of TIMP-1 inhibits cell migration, invasion, and metastatic colonization in lung adenocarcinoma [J].
Chang, Ying-Hua ;
Chiu, Yi-Jen ;
Cheng, Hung-Chi ;
Liu, Fang-Ju ;
Lai, Wu-Wei ;
Chang, Hsiao-Jen ;
Liao, Pao-Chi .
TUMOR BIOLOGY, 2015, 36 (05) :3957-3967
[7]   Aquaporin 3 promotes prostate cancer cell motility and invasion via extracellular signal-regulated kinase 1/2-mediated matrix metalloproteinase-3 secretion [J].
Chen, Jie ;
Wang, Zhijun ;
Xu, Danfeng ;
Liu, Yushan ;
Gao, Yi .
MOLECULAR MEDICINE REPORTS, 2015, 11 (04) :2882-2888
[8]   MiR-1246 promotes SiHa cervical cancer cell proliferation, invasion, and migration through suppression of its target gene thrombospondin 2 [J].
Chen, Junying ;
Yao, Desheng ;
Zhao, Shan ;
He, Chanjuan ;
Ding, Nan ;
Li, Li ;
Long, Fengyi .
ARCHIVES OF GYNECOLOGY AND OBSTETRICS, 2014, 290 (04) :725-732
[9]   Enhanced metastatic dissemination to multiple organs by melanoma and lymphoma cells in timp-3-/- mice [J].
Cruz-Munoz, W. ;
Sanchez, O. H. ;
Di Grappa, M. ;
English, J. L. ;
Hill, R. P. ;
Khokha, R. .
ONCOGENE, 2006, 25 (49) :6489-6496
[10]   TIMP-3 deficiency in the host, but not in the tumor, enhances tumor growth and angiogenesis [J].
Cruz-Muñoz, W ;
Kim, I ;
Khokha, R .
ONCOGENE, 2006, 25 (04) :650-655