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Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2011

Open Access 01-12-2011 | Short report

Altered protein expression in serum from endometrial hyperplasia and carcinoma patients

Authors: Yi-sheng Wang, Rui Cao, Hong Jin, Yi-ping Huang, Xiao-yan Zhang, Qing Cong, Yi-feng He, Cong-jian Xu

Published in: Journal of Hematology & Oncology | Issue 1/2011

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Abstract

Background

Endometrial carcinoma is one of the most common gynecological malignancies in women. The diagnosis of the disease at early or premalignant stages is crucial for the patient's prognosis. To date, diagnosis and follow-up of endometrial carcinoma and hyperplasia require invasive procedures. Therefore, there is considerable demand for the identification of biomarkers to allow non-invasive detection of these conditions.

Methods

In this study, we performed a quantitative proteomics analysis on serum samples from simple endometrial hyperplasia, complex endometrial hyperplasia, atypical endometrial hyperplasia, and endometrial carcinoma patients, as well as healthy women. Serum samples were first depleted of high-abundance proteins, labeled with isobaric tags (iTRAQ™), and then analyzed via two-dimensional liquid chromatography and tandem mass spectrometry. Protein identification and quantitation information were acquired by comparing the mass spectrometry data against the International Protein Index Database using ProteinPilot software. Bioinformatics annotation of identified proteins was performed by searching against the PANTHER database.

Results

In total, 74 proteins were identified and quantified in serum samples from endometrial lesion patients and healthy women. Using a 1.6-fold change as the benchmark, 12 proteins showed significantly altered expression levels in at least one disease group compared with healthy women. Among them, 7 proteins were found, for the first time, to be differentially expressed in atypical endometrial hyperplasia. These proteins are orosomucoid 1, haptoglobin, SERPINC 1, alpha-1-antichymotrypsin, apolipoprotein A-IV, inter-alpha-trypsin inhibitor heavy chain H4, and histidine-rich glycoprotein.

Conclusions

The differentially expressed proteins we discovered in this study may serve as biomarkers in the diagnosis and follow-up of endometrial hyperplasia and endometrial carcinoma.
Appendix
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Literature
1.
2.
Plataniotis G, Castiglione M, Grp EGW: Endometrial cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology. 2010, 21: v41-v45. 10.1093/annonc/mdq245.CrossRefPubMed
3.
Liu B, Nash J, Runowicz C, Swede H, Stevens R, Li ZH: Ovarian cancer immunotherapy: opportunities, progresses and challenges. Journal of Hematology & Oncology. 2010, 3:
4.
DeSouza L, Diehl G, Rodrigues MJ, Guo J, Romaschin AD, Colgan TJ, Siu KW: Search for cancer markers from endometrial tissues using differentially labeled tags iTRAQ and cICAT with multidimensional liquid chromatography and tandem mass spectrometry. J Proteome Res. 2005, 4: 377-386. 10.1021/pr049821j.CrossRefPubMed
5.
Li H, DeSouza LV, Ghanny S, Li W, Romaschin AD, Colgan TJ, Siu KWM: Identification of Candidate Biomarker Proteins Released by Human Endometrial and Cervical Cancer Cells Using Two-Dimensional Liquid Chromatography/Tandem Mass Spectrometry. J Proteome Res. 2007, 6: 2615-2622. 10.1021/pr0700798.CrossRefPubMed
6.
Abdul-Rahman PS, Lim BK, Hashim OH: Expression of high-abundance proteins in sera of patients with endometrial and cervical cancers: Analysis using 2-DE with silver staining and lectin detection methods. ELECTROPHORESIS. 2007, 28: 1989-1996. 10.1002/elps.200600629.CrossRefPubMed
7.
Yang ECC, Guo J, Diehl G, DeSouza L, Rodrigues MJ, Romaschin AD, Colgan TJ, Siu KWM: Protein Expression Profiling of Endometrial Malignancies Reveals a New Tumor Marker: Chaperonin 10. Journal of Proteome Research. 2004, 3: 636-643. 10.1021/pr049975z.CrossRefPubMed
8.
DeSouza LV, Grigull J, Ghanny S, Dube V, Romaschin AD, Colgan TJ, Siu KW: Endometrial carcinoma biomarker discovery and verification using differentially tagged clinical samples with multidimensional liquid chromatography and tandem mass spectrometry. Mol Cell Proteomics. 2007, 6: 1170-1182. 10.1074/mcp.M600378-MCP200.CrossRefPubMed
9.
Zhu LR, Zhang WY, Yu L, Zheng YH, Zhang JZ, Liao QP: Serum proteomic features for detection of endometrial cancer. Int J Gynecol Cancer. 2006, 16: 1374-1378. 10.1111/j.1525-1438.2006.00561.x.CrossRefPubMed
10.
Yoshizaki T, Enomoto T, Nakashima R, Ueda Y, Kanao H, Yoshino K, Fukumoto M, Yoneda Y, Buzard GS, Murata Y: Altered protein expression in endometrial carcinogenesis. Cancer Letters. 2005, 226: 101-106. 10.1016/j.canlet.2004.11.053.CrossRefPubMed
11.
Guo J, Colgan TJ, DeSouza LV, Rodrigues MJ, Romaschin AD, Siu KWM: Direct analysis of laser capture microdissected endometrial carcinoma and epithelium by matrix-assisted laser desorption/ionization mass spectrometry. Rapid Communications in Mass Spectrometry. 2005, 19: 2762-2766. 10.1002/rcm.2119.CrossRefPubMed
12.
Byrjalsen I, Mose Larsen P, Fey SJ, Nilas L, Larsen MR, Christiansen C: Two-dimensional gel analysis of human endometrial proteins: characterization of proteins with increased expression in hyperplasia and adenocarcinoma. Mol Hum Reprod. 1999, 5: 748-756. 10.1093/molehr/5.8.748.CrossRefPubMed
13.
Takano M, Kikuchi Y, Asakawa T, Goto T, Kita T, Kudoh K, Kigawa J, Sakuragi N, Sakamoto M, Sugiyama T, Yaegashi N, Tsuda H, Seto H, Shiwa M: Identification of potential serum markers for endometrial cancer using protein expression profiling. J Cancer Res Clin Oncol. 2010, 136: 475-481. 10.1007/s00432-009-0680-7.CrossRefPubMed
14.
Li ZY, Min WJ, Huang CH, Bai SJ, Tang MH, Zhao X: Proteomics-Based Approach Identified Differentially Expressed Proteins With Potential Roles in Endometrial Carcinoma. Int J Gynecol Cancer. 2010, 20: 9-15. 10.1111/IGC.0b013e3181a9026d.CrossRefPubMed
15.
Yurkovetsky Z, Ta'asan S, Skates S, Rand A, Lomakin A, Linkov F, Marrangoni A, Velikokhatnaya L, Winans M, Gorelik E, Maxwell GL, Lu K, Lokshin A: Development of multimarker panel for early detection of endometrial cancer. High diagnostic power of prolactin. Gynecologic Oncology. 2007, 107: 58-65. 10.1016/j.ygyno.2007.05.041.PubMedCentralCrossRefPubMed
16.
Negishi A, Ono M, Handa Y, Kato H, Yamashita K, Honda K, Shitashige M, Satow R, Sakuma T, Kuwabara H, Omura K, Hirohashi S, Yamada T: Large-scale quantitative clinical proteomics by label-free liquid chromatography and mass spectrometry. Cancer Sci. 2009, 100: 514-519. 10.1111/j.1349-7006.2008.01055.x.CrossRefPubMed
17.
Li ZY, Zhao X, Bai SJ, Wang Z, Chen LJ, Wei YQ, Huang CH: Proteomics Identification of Cyclophilin A as a Potential Prognostic Factor and Therapeutic Target in Endometrial Carcinoma. Mol Cell Proteomics. 2008, 7: 1810-1823. 10.1074/mcp.M700544-MCP200.CrossRefPubMed
18.
Zieske LR: A perspective on the use of iTRAQTM reagent technology for protein complex and profiling studies. J Exp Bot. 2006, 57: 1501-1508. 10.1093/jxb/erj168.CrossRefPubMed
19.
Hergenroeder G, Redell JB, Moore AN, Dubinsky WP, Funk RT, Crommett J, Clifton GL, Levine R, Valadka A, Dash PK: Identification of serum biomarkers in brain-injured adults: Potential for predicting elevated intracranial pressure. Journal of Neurotrauma. 2008, 25: 79-93. 10.1089/neu.2007.0386.CrossRefPubMed
20.
Chen Y, Lim BK, Hashim OH: Different altered stage correlative expression of high abundance acute-phase proteins in sera of patients with epithelial ovarian carcinoma. Journal of Hematology & Oncology. 2009, 2: 37-CrossRef
21.
Mohamed E, Abdul-Rahman PS, Doustjaialil SR, Chen Y, Lim BK, Omar SZ, BustaM AZ, Singh VA, Mohd-Taib N, Yip CH, Hashim OH: Lectin-based electrophoretic analysis of the expression of the 35 kDa inter-alpha-trypsin inhibitor heavy chain H4 fragment in sera of patients with five different malignancies. Electrophoresis. 2008, 29: 2645-2650. 10.1002/elps.200700828.CrossRefPubMed
22.
Uhlar CM, Whitehead AS: Serum amyloid A, the major vertebrate acute-phase reactant. European Journal of Biochemistry. 1999, 265: 501-523. 10.1046/j.1432-1327.1999.00657.x.CrossRefPubMed
23.
Malle E, Sodin-Semrl S, Kovacevic A: Serum amyloid A: An acute-phase protein involved in tumour pathogenesis. Cellular and Molecular Life Sciences. 2009, 66: 9-26. 10.1007/s00018-008-8321-x.CrossRefPubMed
24.
Gutfeld O, Prus D, Ackerman Z, Dishon S, Linke RP, Levin M, Urieli-Shoval S: Expression of serum amyloid A, in normal, dysplastic, and neoplastic human colonic mucosa: implication for a role in colonic tumorigenesis. J Histochem Cytochem. 2006, 54: 63-73. 10.1369/jhc.5A6645.2005.CrossRefPubMed
25.
Dube V, Grigull J, DeSouza LV, Ghanny S, Colgan TJ, Romaschin AD, Siu KW: Verification of endometrial tissue biomarkers previously discovered using mass spectrometry-based proteomics by means of immunohistochemistry in a tissue microarray format. J Proteome Res. 2007, 6: 2648-2655. 10.1021/pr070087o.CrossRefPubMed
26.
Wong YF, Cheung TH, Lo KWK, Yim SF, Siu NSS, Chan SCS, Ho TWF, Wong KWY, Yu MY, Wang VW, Li C, Gardner GJ, Bonome T, Johnson WB, Smith DI, Chung TKH, Birrer MJ: Identification of molecular markers and signaling pathway in endometrial cancer in Hong Kong Chinese women by genome-wide gene expression profiling. Oncogene. 2007, 26: 1971-1982. 10.1038/sj.onc.1209986.CrossRefPubMed
27.
Tsuchida-Straeten N, Ensslen S, Schafer C, Woltje M, Denecke B, Moser M, Graber S, Wakabayashi S, Koide T, Jahnen-Dechent W: Enhanced blood coagulation and fibrinolysis in mice lacking histidine-rich glycoprotein (HRG). J Thromb Haemost. 2005, 3: 865-872. 10.1111/j.1538-7836.2005.01238.x.CrossRefPubMed
28.
Rydengard V, Olsson AK, Morgelin M, Schmidtchen A: Histidine-rich glycoprotein exerts antibacterial activity. Febs Journal. 2007, 274: 377-389. 10.1111/j.1742-4658.2006.05586.x.CrossRefPubMed
29.
Olsson AK, Larsson H, Dixelius J, Johansson I, Lee C, Oellig C, Bjork I, Claesson-Welsh L: A fragment of histidine-rich glycoprotein is a potent inhibitor of tumor vascularization. Cancer research. 2004, 64: 599-605. 10.1158/0008-5472.CAN-03-1941.CrossRefPubMed
30.
Shah A, Singh H, Sachdev V, Lee J, Yotsukura S, Salgia R, Bharti A: Differential Serum Level of Specific Haptoglobin Isoforms in Small Cell Lung Cancer. Current Proteomics. 2010, 7: 49-56. 10.2174/157016410790979635.PubMedCentralCrossRefPubMed
31.
Neale EJ, Wong WSF, Arumanayagam M, Chang MZA: The Clinical-Significance of the Serum Haptoglobin Concentration in Patients with Invasive Cervical-Carcinoma. Aust N Z J Obstet Gynaecol. 1989, 29: 197-199. 10.1111/j.1479-828X.1989.tb01718.x.CrossRefPubMed
32.
Nabli H, Tuller E, Sharpe-Timms KL: Haptoglobin Expression in Endometrioid Adenocarcinoma of the Uterus. Reproductive Sciences. 2010, 17: 47-55. 10.1177/1933719109346331.CrossRefPubMed
33.
Weiderpass E, Brismar K, Bellocco R, Vainio H, Kaaks R: Serum levels of insulin-like growth factor-I, IGF-binding protein 1 and 3, and insulin and endometrial cancer risk. Br J Cancer. 2003, 89: 1697-1704. 10.1038/sj.bjc.6601312.PubMedCentralCrossRefPubMed
34.
Hirano S, Ito N, Takahashi S, Tamaya T: Clinical implications of insulin-like growth factors through the presence of their binding proteins and receptors expressed in gynecological cancers. Eur J Gynaecol Oncol. 2004, 25: 187-191.PubMed
35.
Thongboonkerd V: Genomics, proteomics and integrative 'omics' in hypertension research. [Miscellaneous Article]. Current Opinion in Nephrology & Hypertension. 2005, 14: 133-139.CrossRef
36.
Bradford MM: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical Biochemistry. 1976, 72: 248-254. 10.1016/0003-2697(76)90527-3.CrossRefPubMed
37.
Song X, Bandow J, Sherman J, Baker JD, Brown PW, McDowell MT, Molloy MP: iTRAQ experimental design for plasma biomarker discovery. J Proteome Res. 2008, 7: 2952-2958. 10.1021/pr800072x.CrossRefPubMed
Metadata
Title
Altered protein expression in serum from endometrial hyperplasia and carcinoma patients
Authors
Yi-sheng Wang
Rui Cao
Hong Jin
Yi-ping Huang
Xiao-yan Zhang
Qing Cong
Yi-feng He
Cong-jian Xu
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2011
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/1756-8722-4-15

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