Skip to main content
Log in

Preliminary study of the urinary proteome in Li and Han ethnic individuals from Hainan

  • Research Paper
  • Published:
Science China Life Sciences Aims and scope Submit manuscript

Abstract

Biomarkers indicate changes associated with disease. Blood is relatively stable due to the homeostatic mechanisms of the body; however, urine accumulates metabolites from changes in the body, making it a better source for early biomarker discovery. The Li ethnic group is a unique minority ethnic group that has only lived on Hainan Island for approximately 5,000 years. Studies have shown that various specific genetic variations are different between the Li and Han ethnic groups. However, whether the urinary proteome between these two ethnic groups is significantly different remains unknown. In this study, differential urinary proteins were identified in the Li and Han ethnic groups using liquid chromatography tandem mass spectrometry (LC-MS/MS). In total, 1,555 urinary proteins were identified. Twenty-five of the urinary proteins were statistically significantly different, 16 of which have been previously reported to be biomarkers of many diseases, and that these significantly different proteins were caused by ethnic differences rather than random differences. Ethnic group differences may be an influencing factor in urine proteome studies and should be considered when human urine samples are used for biomarker discovery.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Albert, C., Albert, A., Kube, J., Bellomo, R., Wettersten, N., Kuppe, H., Westphal, S., Haase, M., and Haase-Fielitz, A. (2018). Urinary biomarkers may provide prognostic information for subclinical acute kidney injury after cardiac surgery. J Thoracic Cardiovasc Surg 155, 2441–2452.e13.

    CAS  Google Scholar 

  • An, M., and Gao, Y. (2015). Urinary biomarkers of brain diseases. Genom Proteom Bioinform 13, 345–354.

    Google Scholar 

  • Arner, P., Henjes, F., Schwenk, J.M., Darmanis, S., Dahlman, I., Iresjö, B. M., Naredi, P., Agustsson, T., Lundholm, K., Nilsson, P., et al. (2015). Circulating carnosine dipeptidase 1 associates with weight loss and poor prognosis in gastrointestinal cancer. PLoS ONE 10, e0123566.

    PubMed  PubMed Central  Google Scholar 

  • Aslebagh, R., Channaveerappa, D., Arcaro, K.F., and Darie, C.C. (2018). Proteomics analysis of human breast milk to assess breast cancer risk. Electrophoresis 39, 653–665.

    CAS  PubMed  Google Scholar 

  • Azurmendi, L., Lapierre-Fetaud, V., Schneider, J., Montaner, J., Katan, M., and Sanchez, J.C. (2017). Proteomic discovery and verification of serum amyloid A as a predictor marker of patients at risk of post-stroke infection: a pilot study. Clin Proteom 14, 27.

    CAS  Google Scholar 

  • Bellei, E., Rossi, E., Lucchi, L., Uggeri, S., Albertazzi, A., Tomasi, A., and Iannone, A. (2008). Proteomic analysis of early urinary biomarkers of renal changes in type 2 diabetic patients. Prot Clin Appl 2, 478–491.

    CAS  Google Scholar 

  • Beretov, J., Wasinger, V.C., Millar, E.K.A., Schwartz, P., Graham, P.H., and Li, Y. (2015). Proteomic analysis of urine to identify breast cancer biomarker candidates using a label-free LC-MS/MS approach. PLoS ONE 10, e0141876.

    PubMed  PubMed Central  Google Scholar 

  • Bracht, T., Schweinsberg, V., Trippler, M., Kohl, M., Ahrens, M., Padden, J., Naboulsi, W., Barkovits, K., Megger, D.A., Eisenacher, M., et al. (2015). Analysis of disease-associated protein expression using quantitative proteomics—Fibulin-5 is expressed in association with hepatic fibrosis. J Proteome Res 14, 2278–2286.

    CAS  PubMed  Google Scholar 

  • Buanes, T.A. (2016). Updated therapeutic outcome for patients with periampullary and pancreatic cancer related to recent translational research. World J Gastroenterol 22, 10502–10511.

    PubMed  PubMed Central  Google Scholar 

  • Capo-chichi, C.D., Aguida, B., Chabi, N.W., Cai, Q.K., Offrin, G., Agossou, V.K., Sanni, A., and Xu, X.X. (2016). Lamin A/C deficiency is an independent risk factor for cervical cancer. Cell Oncol 39, 59–68.

    CAS  Google Scholar 

  • Chan, H.H., Rahim, Z.H.A., Jessie, K., Hashim, O.H., and Taiyeb-Ali, T.B. (2012). Salivary proteins associated with periodontitis in patients with type 2 diabetes mellitus. Int J Mol Sci 13, 4642–4654.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chen, S.L., Lu, S.X., Liu, L.L., Wang, C.H., Yang, X., Zhang, Z.Y., Zhang, H.Z., and Yun, J.P. (2018). eEF1A1 overexpression enhances tumor progression and indicates poor prognosis in hepatocellular carcinoma. Transl Oncol 11, 125–131.

    PubMed  Google Scholar 

  • Chen, T., Guo, M., Gao, Y., Chen, F., Guo, J., Liu, T., Wu, D., and Jiang, X. (2014). A comparative study on the levels of serum cytokines and cortisol among post-traumatic stress disorder patients of Li and Han ethnicities in Hainan. Chin Med J 127, 2771–2774.

    CAS  PubMed  Google Scholar 

  • Cho-Vega, J.H., Tsavachidis, S., Do, K.A., Nakagawa, J., Medeiros, L.J., and McDonnell, T.J. (2007). Dicarbonyl/L-xylulose reductase: a potential biomarker identified by laser-capture microdissection-micro serial analysis of gene expression of human prostate adenocarcinoma. Cancer Epidemiol Biomark Prevent 16, 2615–2622.

    CAS  Google Scholar 

  • Chu, Y., Lai, Y. H., Lee, M. C., Yeh, Y. J., Wu, Y. K., Tsao, W., Huang, C. Y., and Wu, S. (2017). Calsyntenin-1, clusterin and neutrophil gelatinase-associated lipocalin are candidate serological biomarkers for lung adenocarcinoma. Oncotarget 8, 107964–107976.

    PubMed  PubMed Central  Google Scholar 

  • Ding, Y., He, P., He, N., Li, Q., Sun, J., Yao, J., Yi, S., Xu, H., Wu, D., Wang, X., et al. (2016). Genetic polymorphisms of pharmacogenomic VIP variants in Li nationality of southern China. Environ Toxicol Pharmacol 42, 237–242.

    CAS  PubMed  Google Scholar 

  • Ding, Y., Yang, D., Zhou, L., He, P., Yao, J., Xie, P., Lin, D., Sun, D., Sun, P., Li, Q., et al. (2015a). Cytochrome P450 2C9 (CYP2C9) polymorphisms in Chinese Li population. Int J Clin Exp Med 8, 21024–21033.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ding, Y., Yang, D., Zhou, L., Xu, J., Chen, Y., He, P., Yao, J., Chen, J., Niu, H., Sun, P., et al. (2015b). Variants in multiple genes polymorphism association analysis of COPD in the Chinese Li population. Int J Chron Obstruct Pulmon Dis 10, 1455–1463.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Eisenach, P.A., Soeth, E., Röder, C., Klöppel, G., Tepel, J., Kalthoff, H., and Sipos, B. (2013). Dipeptidase 1 (DPEP1) is a marker for the transition from low-grade to high-grade intraepithelial neoplasia and an adverse prognostic factor in colorectal cancer. Br J Cancer 109, 694–703.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gajbhiye, A., Dabhi, R., Taunk, K., Vannuruswamy, G., RoyChoudhury, S., Adhav, R., Seal, S., Mane, A., Bayatigeri, S., Santra, M.K., et al. (2016). Urinary proteome alterations in HER2 enriched breast cancer revealed by multipronged quantitative proteomics. Proteomics 16, 2403–2418.

    CAS  PubMed  Google Scholar 

  • Gala-Błądzińska, A., Żyłka, A., Dumnicka, P., Kuśnierz-Cabala, B., Kaziuk, M.B., and Kuźniewski, M. (2017). Sterile leukocyturia affects urine neutrophil gelatinase-associated lipocalin concentration in type 2 diabetic patients. Arch Med Sci 2, 321–327.

    Google Scholar 

  • Gao, Y.H. (2013). Urine—an untapped goldmine for biomarker discovery? Sci China Life Sci 56, 1145–1146.

    PubMed  Google Scholar 

  • Gao, Y. (2014). Roadmap to the urine biomarker era. MOJ Proteom Bioinform 1, 00005.

    Google Scholar 

  • Greco, S.A., Chia, J., Inglis, K.J., Cozzi, S.J., Ramsnes, I., Buttenshaw, R. L., Spring, K.J., Boyle, G.M., Worthley, D.L., Leggett, B.A., et al. (2010). Thrombospondin-4 is a putative tumour-suppressor gene in colorectal cancer that exhibits age-related methylation. BMC Cancer 10, 494.

    PubMed  PubMed Central  Google Scholar 

  • Guo, Z., Liu, X., Li, M., Shao, C., Tao, J., Sun, W., and Li, M. (2015a). Differential urinary glycoproteome analysis of type 2 diabetic nephropathy using 2D-LC-MS/MS and iTRAQ quantification. J Transl Med 13, 371.

    PubMed  PubMed Central  Google Scholar 

  • Guo, Z., Zhang, Y., Zou, L., Wang, D., Shao, C., Wang, Y., Sun, W., and Zhang, L. (2015b). A proteomic analysis of individual and gender variations in normal human urine and cerebrospinal fluid using iTRAQ quantification. PLoS ONE 10, e0133270.

    PubMed  PubMed Central  Google Scholar 

  • Hauck, S.M., Dietter, J., Kramer, R.L., Hofmaier, F., Zipplies, J.K., Amann, B., Feuchtinger, A., Deeg, C.A., and Ueffing, M. (2010). Deciphering membrane-associated molecular processes in target tissue of autoimmune uveitis by label-free quantitative mass spectrometry. Mol Cell Proteomics 9, 2292–2305.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Huang, J.T.J., Chaudhuri, R., Albarbarawi, O., Barton, A., Grierson, C., Rauchhaus, P., Weir, C.J., Messow, M., Stevens, N., McSharry, C., et al. (2012). Clinical validity of plasma and urinary desmosine as biomarkers for chronic obstructive pulmonary disease. Thorax 67, 502–508.

    PubMed  Google Scholar 

  • Jeong, H.C., Kim, G.I., Cho, S.H., Lee, K.H., Ko, J.J., Yang, J.H., and Chung, K.H. (2011). Proteomic analysis of human small cell lung cancer tissues: up-regulation of coactosin-like protein-1. J Proteome Res 10, 269–276.

    CAS  PubMed  Google Scholar 

  • Jia, L.L., Liu, X.J., Liu, L., Li, M.X., and Gao, Y.H. (2014). Urimem, a membrane that can store urinary proteins simply and economically, makes the large-scale storage of clinical samples possible. Sci China Life Sci 57, 336–339.

    PubMed  Google Scholar 

  • Ward, B.J., Kardoush, M.I., and Ndao, M. (2017). Serum carbonic anhydrase 1 is a biomarker for diagnosis of human schistosoma mansoni infection. Am J Tropical Med Hygiene 96, 842–849.

    Google Scholar 

  • Koch, M., Mitulovic, G., Hanzal, E., Umek, W., Seyfert, S., Mohr, T., Koelbl, H., and Laterza, R.M. (2016). Urinary proteomic pattern in female stress urinary incontinence: a pilot study. Int Urogynecol J 27, 1729–1734.

    PubMed  PubMed Central  Google Scholar 

  • Krzemien, G., Panczyk-Tomaszewska, M., Adamczuk, D., Kotula, I., Demkow, U., and Szmigielska, A. (2018). Neutrophil gelatinase-associated lipocalin: a biomarker for early diagnosis of urinary tract infections in infants. Adv Exp Med Biol 1047, 71–80.

    CAS  PubMed  Google Scholar 

  • Li, L., Cui, Y., Ji, J.F., and Jiang, W.G. (2017). Clinical correlation between WISP2 and beta-catenin in gastric cancer. Anticancer Res 37, 4469–4473.

    CAS  PubMed  Google Scholar 

  • Li, M.L., Zhao, M.D., and Gao, Y.H. (2014). Changes of proteins induced by anticoagulants can be more sensitively detected in urine than in plasma. Sci China Life Sci 57, 649–656.

    CAS  PubMed  Google Scholar 

  • Liu, E., Nisenblat, V., Farquhar, C., Fraser, I., Bossuyt, P.M., Johnson, N., and Hull, M.L. (2015). Urinary biomarkers for the non-invasive diagnosis of endometriosis. The Cochrane Database of Systematic Reviews, CD012019.

  • Liu, Z., Ma, Y., Yang, J., and Qin, H. (2011). Upregulated and downregulated proteins in hepatocellular carcinoma: a systematic review of proteomic profiling studies. Omics 15, 61–71.

    PubMed  Google Scholar 

  • Lubell, T.R., Barasch, J.M., Xu, K., Ieni, M., Cabrera, K.I., and Dayan, P.S. (2017). Urinary neutrophil gelatinase-associated lipocalin for the diagnosis of urinary tract infections. Pediatrics 140.

  • Matsumoto, K.I., Maniwa, T., Tanaka, T., Satoh, K., Okunishi, H., and Oda, T. (2012). Proteomic analysis of calcified abdominal and thoracic aortic aneurysms. Int J Mol Med 30, 417–429.

    CAS  PubMed  Google Scholar 

  • Morrissey, J.J., London, A.N., Lambert, M.C., and Kharasch, E.D. (2011). Sensitivity and specificity of urinary neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 for the diagnosis of renal cell carcinoma. Am J Nephrol 34, 391–398.

    CAS  PubMed  Google Scholar 

  • Motawi, T.K., Shehata, N.I., ElNokeety, M.M., and El-Emady, Y.F. (2018). Potential serum biomarkers for early detection of diabetic nephropathy. Diabetes Res Clin Pract 136, 150–158.

    CAS  PubMed  Google Scholar 

  • Naboulsi, W., Megger, D.A., Bracht, T., Kohl, M., Turewicz, M., Eisenacher, M., Voss, D.M., Schlaak, J.F., Hoffmann, A.C., Weber, F., et al. (2016). Quantitative tissue proteomics analysis reveals versican as potential biomarker for early-stage hepatocellular carcinoma. J Proteome Res 15, 38–47.

    CAS  PubMed  Google Scholar 

  • Nylund, K.M., Ruokonen, H., Sorsa, T., Heikkinen, A.M., Meurman, J.H., Ortiz, F., Tervahartiala, T., Furuholm, J., and Bostanci, N. (2017). Association of the salivary triggering receptor expressed on myeloid cells/its ligand peptidoglycan recognition protein 1 axis with oral inflammation in kidney disease. J Periodontol, 1–17.

  • Onile, O.S., Calder, B., Soares, N.C., Anumudu, C.I., and Blackburn, J.M. (2017). Quantitative label-free proteomic analysis of human urine to identify novel candidate protein biomarkers for schistosomiasis. PLoS Negl Trop Dis 11, e0006045.

    PubMed  PubMed Central  Google Scholar 

  • Qin, W., and Gao, Y. (2015). Elution of urinary proteins preserved on nitrocellulose membrane with heating (in Chinese). Chin J Biotechnol 31, 1387–1392.

    Google Scholar 

  • Reszka, E. (2012). Selenoproteins in bladder cancer. Clin Chim Acta 413, 847–854.

    CAS  PubMed  Google Scholar 

  • Rohatgi, A., Ayers, C.R., Khera, A., McGuire, D.K., Das, S.R., Matulevicius, S., Timaran, C.H., Rosero, E.B., and de Lemos, J.A. (2009). The association between peptidoglycan recognition protein-1 and coronary and peripheral atherosclerosis: Observations from the Dallas Heart Study. Atherosclerosis 203, 569–575.

    CAS  PubMed  Google Scholar 

  • Sedic, M., Kraljevic Pavelic, S., Cindric, M., Vissers, J.P.C., Peronja, M., Josic, D., Cuk, M., Fumic, K., Pavelic, K., and Baric, I. (2011). Plasma biomarker identification in S-adenosylhomocysteine hydrolase deficiency. Electrophoresis 32, 1970–1975.

    CAS  PubMed  Google Scholar 

  • Shao, C., Li, M., Li, X., Wei, L., Zhu, L., Yang, F., Jia, L., Mu, Y., Wang, J., Guo, Z., et al. (2011). A tool for biomarker discovery in the urinary proteome: a manually curated human and animal urine protein biomarker database. Mol Cell Proteomics 10, M111 010975.

    PubMed  PubMed Central  Google Scholar 

  • Shen, B., Lin, R., Wang, C.C., Rei, J., Sun, Y., Yang, Y.L., and Lin, Y.Y. (2017). ADAM33 gene polymorphisms identified to be associated with asthma in a Chinese Li population. Biomed Rep 6, 323–328.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Shyam, R., Patel, M.L., Sachan, R., Kumar, S., and Pushkar, D.K. (2017). Role of urinary neutrophil gelatinase-associated lipocalin as a biomarker of acute kidney injury in patients with circulatory shock. Ind J Crit Care Med 21, 740–745.

    CAS  Google Scholar 

  • Siddiqi, Z., Karoli, R., Kaul, A., Fatima, J., Varshney, S., and Beg, M.S. (2017). Evaluation of neutrophil gelatinase-associated lipocalin and cystatin C as early markers of diabetic nephropathy. Ann Afr Med 16, 101–106.

    PubMed  PubMed Central  Google Scholar 

  • Silva, S., Bronze, M.R., Figueira, M.E., Siwy, J., Siwy, J., Mischak, H., Combet, E., and Mullen, W. (2015). Impact of a 6-wk olive oil supplementation in healthy adults on urinary proteomic biomarkers of coronary artery disease, chronic kidney disease, and diabetes (types 1 and 2): a randomized, parallel, controlled, double-blind study. Am J Clin Nutrit 101, 44–54.

    CAS  PubMed  Google Scholar 

  • Smith, E.R., Zurakowski, D., Saad, A., Scott, R.M., and Moses, M.A. (2008). Urinary biomarkers predict brain tumor presence and response to therapy. Clin Cancer Res 14, 2378–2386.

    CAS  PubMed  Google Scholar 

  • Tachibana, K., Saito, M., Imai, J.I., Ito, E., Yanagisawa, Y., Honma, R., Saito, K., Ando, J., Momma, T., Ohki, S., et al. (2017). Clinicopathological examination of dipeptidase 1 expression in colorectal cancer. Biomed Rep 6, 423–428.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Toiyama, Y., Inoue, Y., Yasuda, H., Saigusa, S., Yokoe, T., Okugawa, Y., Tanaka, K., Miki, C., and Kusunoki, M. (2011). DPEP1, expressed in the early stages of colon carcinogenesis, affects cancer cell invasiveness. J Gastroenterol 46, 153–163.

    CAS  PubMed  Google Scholar 

  • Valdimarsson, S., Jodal, U., Barregård, L., and Hansson, S. (2017). Urine neutrophil gelatinase-associated lipocalin and other biomarkers in infants with urinary tract infection and in febrile controls. Pediatr Nephrol 32, 2079–2087.

    PubMed  Google Scholar 

  • Wang, D.B., Lu, X.K., Zhang, X., Li, Z.G., and Li, C.X. (2016). Carbonic anhydrase 1 is a promising biomarker for early detection of non-small cell lung cancer. Tumor Biol 37, 553–559.

    CAS  Google Scholar 

  • Willis, N.D., Cox, T.R., Rahman-Casañs, S.F., Smits, K., Przyborski, S.A., van den Brandt, P., van Engeland, M., Weijenberg, M., Wilson, R.G., de Bruïne, A., et al. (2008). Lamin A/C is a risk biomarker in colorectal cancer. PLoS ONE 3, e2988.

    PubMed  PubMed Central  Google Scholar 

  • Wisniewski, J.R., Zougman, A., Nagaraj, N., and Mann, M. (2009). Universal sample preparation method for proteome analysis. Nat Methods 6, 359–362.

    CAS  PubMed  Google Scholar 

  • Wu, J., and Gao, Y. (2015). Physiological conditions can be reflected in human urine proteome and metabolome. Expert Rev Proteomics 12, 623–636.

    CAS  PubMed  Google Scholar 

  • Wu, T., Du, Y., Han, J., Singh, S., Xie, C., Guo, Y., Zhou, X.J., Ahn, C., Saxena, R., and Mohan, C. (2013). Urinary angiostatin—a novel putative marker of renal pathology chronicity in lupus nephritis. Mol Cell Proteomics 12, 1170–1179.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wu, Z., Wu, L., Weng, D., Xu, D., Geng, J., and Zhao, F. (2009). Reduced expression of lamin A/C correlates with poor histological differentiation and prognosis in primary gastric carcinoma. J Exp Clin Cancer Res 28, 8.

    PubMed  PubMed Central  Google Scholar 

  • Yao, H., Chen, X., Lin, L., Wu, C., Fu, X., Wang, H., Yao, Z., Chen, W., Huang, L., Tang, R., et al. (2014). The spectrum of α- and β-thalassemia mutations of the Li people in Hainan Province of China. Blood Cells Mol Dis 53, 16–20.

    CAS  PubMed  Google Scholar 

  • Yao, H.X., Chen, Z.B., and Ding, Y.P. (2002). Serum levels of erythropoietin and transferrin receptor in thalassemia of the Li nationality (in Chinese). J Exp Hematol 10, 483–484.

    Google Scholar 

  • Yin, G.N., Lee, H.W., Cho, J.Y., and Suk, K. (2009). Neuronal pentraxin receptor in cerebrospinal fluid as a potential biomarker for neurodegenerative diseases. Brain Res 1265, 158–170.

    CAS  PubMed  Google Scholar 

  • Zheng, H., Yde, C.C., Clausen, M.R., Kristensen, M., Lorenzen, J., Astrup, A., and Bertram, H.C. (2015). Metabolomics investigation to shed light on cheese as a possible piece in the French paradox puzzle. J Agric Food Chem 63, 2830–2839.

    CAS  PubMed  Google Scholar 

  • Zürbig, P., Decramer, S., Dakna, M., Jantos, J., Good, D.M., Coon, J.J., Bandin, F., Mischak, H., Bascands, J.L., and Schanstra, J.P. (2009). The human urinary proteome reveals high similarity between kidney aging and chronic kidney disease. Proteomics 9, 2108–2117.

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Key Research and Development Program of China (2018YFC0910202, 2016YFC1306300), Beijing Natural Science Foundation (7172076), the Key Basic Research Program of the Ministry of Science and Technology of China (2013FY114100), Beijing Cooperative Construction Project (110651103), Beijing Normal University (11100704), and Peking Union Medical College Hospital (2016-2.27).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Guangliang Shan or Youhe Gao.

Ethics declarations

Compliance and ethics The author(s) declare that they have no conflict of interest. The study was approved by the local Ethics Committee at the Institute of Basic Medical Sciences at the Chinese Academy of Medical Sciences (NO. 029-2013).

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, F., Li, X., Ni, Y. et al. Preliminary study of the urinary proteome in Li and Han ethnic individuals from Hainan. Sci. China Life Sci. 63, 125–137 (2020). https://doi.org/10.1007/s11427-018-9485-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11427-018-9485-4

Keywords

Navigation