Clinical applications of urine proteome based on mass spectrometry

doi:10.16352/j.issn.1001-6325.2025.08.0982

Abstract

Abstract: Urine is stable, non-invasive obtaining and has simple composition. As urine is not regulated by homeostatic mechanisms, it is easier to detect early changes of disease comparing with blood, making urine as an ideal biomarker source. In recent years, with the improvement of mass spectrometry technology and detection throughput, research in the field of clinical urine proteomics has made significant progress. Urine can not only reflect the functional changes of the disease at the tissue level, but also provide a new path for monitoring the efficacy of individualized medication. This review systematically summarizes the research progress of urine proteomics in the diagnosis of non-urinary system diseases in the past decade (2015—2024). This review also discusses the application of urine proteomics in disease monitoring, prognosis evaluation, drug efficacy assesment, and traditional Chinese medicine. Finally,future development prospects of urine proteomics are discussed.

Key words: urine proteomics, biomarkers, early diagnosis, clinical application

CLC Number:

R319

WEI Jing, SUN Wei. Clinical applications of urine proteome based on mass spectrometry[J]. Basic & Clinical Medicine, 2025, 45(8): 982-991.

References

[1] Sun H, Wand D, Liu D, et al. Differential urinary proteins to diagnose coronary heart disease based on iTRAQ quantitative proteomics[J]. Anal Bioanal Chem, 2019, 411: 2273-2282.
[2] Zou L, Wang X, Guo Z, et al. Differential urinary proteomics analysis of myocardial infarction using iTRAQ quantification[J]. Mol Med Rep, 2019, 19: 3972-3988.
[3] Ding W, Qiu B, Cram DS, et al. Isobaric tag for relative and absolute quantitation based quantitative proteomics reveals unique urinary protein profiles in patients with preeclampsia[J]. J Cell Mol Med, 2019, 23: 5822-5826.
[4] Chen R, Yi Y, Xiao W, et al. Label-free liquid chromatography-mass spectrometry proteomic analysis of urinary identification in diabetic vascular dementia in a Han Chinese population[J]. Front Aging Neurosci, 2021, 13: 619945. doi: 10.3389/fnagi.2021.619945.
[5] Starodubeseva NL, Konomokhin AS, Bugrova AE, et al. Investigation of urine proteome of preterm newborns with respiratory pathologies[J]. J Proteomics, 2016, 149:31-37.
[6] Ahmed S, Odumade OA, Van ZP, et al. Urine proteo-mics for noninvasive monitoring of biomarkers in bronchopulmonary dysplasia[J]. Neonatology, 2022, 119: 193-203.
[7] Wu Y, Li M, Zhang K, et al. Quantitative proteomics analysis of serum and urine with DIA mass spectrometry reveals biomarkers for pediatric obstructive sleep apnea[J]. Arch Bronconeumol, 2025,61:67-75.
[8] Liu L, Deng J, Yang Q, et al. Urinary proteomic analysis to identify a potential protein biomarker panel for the diagnosis of tuberculosis[J]. IUBMB Life, 2021, 73: 1073-1083.
[9] Yu J, Yuan J, Liu Z, et al. Combined urine proteomics and metabolomics analysis for the diagnosis of pulmonary tuberculosis[J]. Clin Proteomics, 2024, 21: 66. doi: 10.1186/s12014-024-09514-4.
[10] Zhang C, Leng W, Sun C, et al. Urine proteome profiling predicts lung cancer from control cases and other tumors[J]. EBioMedicine, 2018, 30: 120-128.
[11] Duangkumpha K, Stoll T, Phetcharaburanin J, et al. Urine proteomics study reveals potential biomarkers for the differential diagnosis of cholangiocarcinoma and periductal fibrosis[J]. PLoS One, 2019, 14: e0221024. doi: 10.1371/journal.pone.0221024
[12] Sun Y, Guo Z, Liu X, et al. Noninvasive urinary protein signatures associated with colorectal cancer diagnosis and metastasis[J]. Nat Commun, 2022, 13: 2757. doi: 10.1038/s41467-022-30391-8.
[13] Shimura T, Dayde D, Wang H, et al. Novel urinary protein biomarker panel for early diagnosis of gastric cancer[J]. Br J Cancer, 2020, 123: 1656-1664.
[14] Fan H, Li X, Li ZW, et al. Urine proteomic signatures predicting the progression from premalignancy to malignant gastric cancer[J]. EBioMedicine, 2022, 86:104340. doi: 10.1016/j.ebiom.2022.104340.
[15] Zhao Y, Yang L, Sun C, et al. Discovery of urinary proteomic signature for differential diagnosis of acute appendicitis[J]. Biomed Res Int, 2020, 2020:3896263. doi: 10.1155/2020/3896263.
[16] Akshintala VS, Moore MG, Cruz-Monserrate Z, et al. Urine proteomics profiling identifies novel acute pancrea-titis diagnostic biomarkers in a pediatric population[J]. Gastroenterology, 2024, 167: 1019-1021.e1012. doi: 10.1053/j.gastro.2024.05.015.
[17] Flick KF, Yip-Schneider MT, Sublette CM, et al. A quantitative global proteomics approach identifies candi-date urinary biomarkers that correlate with intraductal papillary mucinous neoplasm dysplasia[J]. Pancreas, 2020, 49: 1044-1051.
[18] Watanabe Y, Hirao Y, Kasuga K, et al. Molecular network analysis of the urinary proteome of Alzheimer's disease patients[J]. Dement Geriatr Cogn Dis Extra, 2019, 9: 53-65.
[19] Watanabe Y, Hirao Y, Kasuga K, et al. Urinary apolipoprotein C3 is a potential biomarker for Alzheimer's disease[J]. Dement Geriatr Cogn Dis Extra, 2020, 10: 94-104.
[20] Wang Y, Sun Y, Wang Y, et al. Identification of novel diagnostic panel for mild cognitive impairment and Alzheimer's disease: findings based on urine proteomics and machine learning[J]. Alzheimers Res Ther, 2023, 15: 191. doi: 10.1186/s13195-023-01324-4.
[21] Virreira Winter S, Karayel O, Strauss MT, et al. Urinary proteome profiling for stratifying patients with familial Parkinson's disease[J]. EMBO Mol Med, 2021, 13: e13257. doi: 10.15252/emmm.202013257.
[22] Wang Y, Zhang J, Song W, et al. A proteomic analysis of urine biomarkers in autism spectrum disorder[J]. J Proteomics, 2021, 242:104259. doi: 10.1016/j.jprot.2021.104259.
[23] Meng W, Huan Y, Gao Y. Urinary proteome profiling for children with autism using data-independent acquisition proteomics[J]. Transl Pediatr, 2021, 10: 1765-1778.
[24] Wu J, Zhang J, Wei J, et al. Urinary biomarker discovery in gliomas using mass spectrometry-based clinical proteomics[J]. Chin Neurosurg J, 2020, 6:11. doi: 10.1186/s41016-020-00190-5.
[25] Hallal SM, Tüzesi Á, Sida LA, et al. Glioblastoma biomarkers in urinary extracellular vesicles reveal the potential for a ‘liquid gold’ biopsy[J]. Br J Cancer, 2024, 130: 836-851.
[26] Hao X, Guo Z, Sun H, et al. Urinary protein biomarkers for pediatric medulloblastoma[J]. J Proteomics, 2020, 225:103832. doi: 10.1016/j.jprot.2020.103832.
[27] Benabdelkamel H, Masood A, Okla M, et al. A proteomics-based approach reveals differential regulation of urine proteins between metabolically healthy and unhealthy obese patients[J]. Int J Mol Sci, 2019, 20: 4905. doi: 10.3390/ijms20194905.
[28] Liu CH, Zheng S, Wang S, et al. Urine proteome in distinguishing hepatic steatosis in patients with metabolic-associated fatty liver disease[J]. Diagnostics (Basel), 2022, 12: 1412. doi: 10.3390/diagnostics12061412.
[29] Xiao K, Yu L, Zhu L, et al. Urine proteomics profiling and functional characterization of knee osteoarthritis using iTRAQ technology[J]. Horm Metab Res, 2019, 51: 735-740.
[30] Carneiro A, Macedo-da-Silva J, Santiago VF, et al. Urine proteomics as a non-invasive approach to monitor exertional rhabdomyolysis during military training[J]. J Proteomics, 2022, 258:104498. doi: 10.1016/j.jprot.2022.104498.
[31] Xu N, Yu Y, Duan C, et al. Quantitative proteomics identifies and validates urinary biomarkers of rhabdomyosarcoma in children[J]. Clin Proteomics, 2023, 20: 10. doi: 10.1186/s12014-023-09401-4.
[32] Morales M, Alayi TD, Tawalbeh SM, et al. Urine proteomics by mass spectrometry identifies proteins involved in key pathogenic pathways in patients with juvenile dermatomyositis[J]. Rheumatology (Oxford), 2023, 62: 3161-3168.
[33] Kacírová M, Bober P, AlexoviČ M, et al. Differential urinary proteomic analysis of endometrial cancer[J]. Physiol Res, 2019, 68(Suppl 4): S483-S490. doi: 10.33549/physiolres.934375.
[34] Njoku K, Pierce A, Geary B, et al. Quantitative SWATH-based proteomic profiling of urine for the identification of endometrial cancer biomarkers in symptomatic women[J]. Br J Cancer, 2023, 128: 1723-1732.
[35] Višnić A, Barišić D, Čanadi Jurešić G, et al. Identification of urine biomarkers of endometriosis-protein mass spectrometry[J]. Am J Reprod Immunol, 2024, 91: e13856. doi: 10.1111/aji.13856.
[36] Tian W, Zhang N, Jin R, et al. Immune suppression in the early stage of COVID-19 disease[J]. Nat Commun, 2020, 11: 5859. doi: 10.1038/s41467-020-19706-9.
[37] Wilson L, Chang JW, Meier S, et al. Proteomic profiling of urine from hospitalized patients with severe pneumonia due to SARS-CoV-2 vs other causes: a preliminary report[J]. Open Forum Infect Dis, 2023, 10: ofad451. doi: 10.1093/ofid/ofad451.
[38] Li Y, Wang Y, Liu H, et al. Urine proteome of COVID-19 patients[J]. Urine (Amst), 2020, 2:1-8.
[39] Liu Y, Song L, Zheng N, et al. A urinary proteomic landscape of COVID-19 progression identifies signaling pathways and therapeutic options[J]. Sci China Life Sci, 2022, 65: 1866-1880.
[40] Bi X, Liu W, Ding X, et al. Proteomic and metabolomic profiling of urine uncovers immune responses in patients with COVID-19[J]. Cell Rep, 2022, 38: 110271. doi: 10.1016/j.celrep.2021.110271.
[41] Hu HM, Du HW, Cui JW, et al. New biomarkers of Kawasaki disease identified by urine proteomic analysis[J]. FEBS Open Bio, 2019, 9: 265-275.
[42] Liu N, Wang J, Wang X, et al. Analysis of urine differential proteins in patients with allergic rhinitis[J]. Heliyon, 2023, 9: e17323. doi: 10.1016/j.heliyon.2023.e17323.
[43] Qin W, Liang A, Han X, et al. Quantitative urinary proteome analysis reveals potential biomarkers for disease activity of Behçet's disease uveitis[J]. BMC Ophthalmol, 2024, 24: 277. doi: 10.1186/s12886-024-03557-9.
[44] Jeanmard N, Bissanum R, Sriplung H, et al. Proteomic profiling of urinary extracellular vesicles differentiates breast cancer patients from healthy women[J]. PLoS One, 2023, 18: e0291574. doi: 10.1371/journal.pone.0291574.
[45] Fu W, Song Y, Zhao R, et al. Proteomics analysis of serum and urine identifies VCP and CTSA as potential biomarkers associated with multiple myeloma[J]. Clin Chim Acta, 2024, 552: 117701. doi: 10.1016/j.cca.2023.117701.
[46] Ortiz MV, Ahmed S, Burns M, et al. Prohibitin is a prognostic marker and therapeutic target to block chemotherapy resistance in Wilms' tumor[J]. JCI Insight, 2019, 4: e127098. doi: 10.1172/jci.insight.127098.
[47] Pang B, Wang Q, Chen H, et al. Proteomic identification of small extracellular vesicle proteins LAMB1 and histone H4 for prostate cancer diagnosis and risk stratification[J]. Adv Sci (Weinh), 2024, 11: e2402509. doi: 10.1002/advs.202402509.
[48] Doykov ID, Heywood WE, Nikolaenko V, et al. Rapid, proteomic urine assay for monitoring progressive organ disease in Fabry disease[J]. J Med Genet, 2020, 57: 38-47.
[49] Song H, Hu Z, Zhang S, et al. Application of urine proteomics in the diagnosis and treatment effectiveness monitoring of early-stage mycosis fungoides[J]. Clin Proteomics, 2024, 21: 53. doi: 10.1186/s12014-024-09503-7
[50] Huan Y, Wei J, Zhou J, et al. Label-free liquid chromatography-mass spectrometry proteomic analysis of the urinary proteome for measuring the escitalopram treatment response from major depressive disorder[J]. Front Psychiatry, 2021, 12:700149. doi: 10.3389/fpsyt.2021.700149.
[51] Jia L, Wu J, Wei J, et al. Proteomic analysis of urine reveals biomarkers for the diagnosis and phenotyping of abdominal-type Henoch-Schonlein purpura[J]. Transl Pediatr, 2021, 10: 510-524.
[52] Peerapen P, Ausakunpipat N, Sutthimethakorn S, et al. Physiologic changes of urinary proteome by caffeine and excessive water intake[J]. Clin Chem Lab Med, 2017, 55: 993-1002.
[53] Shao C, Zhao M, Chen X, et al. Comprehensive analysis of individual variation in the urinary proteome revealed significant gender differences[J]. Mol Cell Proteomics, 2019, 18: 1110-1122.
[54] Xiao X, Sun H, Liu X, et al. Qualitative and quantitative proteomic and metaproteomic analyses of healthy human urine sediment[J]. Proteomics Clin Appl, 2022, 16: e2100007. doi: 10.1002/prca.202100007.
[55] 中国尿计划共同倡议人, 高友鹤, 孙伟, 等. 中国尿计划倡议书[J]. 中国科学:生命科学, 2025, 55: 393-396.