A1BG and C3 are overexpressed in patients with cervical intraepithelial neoplasia III

Canales,Norma  Angélica Galicia; Marina,Vicente   Madrid; Castro,Jorge  Salmerón; Jiménez,Alfredo  Antúnez; Mendoza‑Hernández,Guillermo; McCarron,Elizabeth   Langley; Roman,Margarita  Bahena; Castro‑Romero,Julieta  Ivone

doi:10.3892/ol.2014.2195

A1BG and C3 are overexpressed in patients with cervical intraepithelial neoplasia III

Authors:
- Norma Angélica Galicia Canales
- Vicente Madrid Marina
- Jorge Salmerón Castro
- Alfredo Antúnez Jiménez
- Guillermo Mendoza‑Hernández
- Elizabeth Langley McCarron
- Margarita Bahena Roman
- Julieta Ivone Castro‑Romero
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Affiliations: Research Center on Infection Diseases, National Institute of Public Health, Cuernavaca, Morelos 62100, Mexico, Epidemiology and Health Services Research Unit, National Institute of Social Security, Cuernavaca, Morelos 62450, Mexico, Laboratory of Peptides and Proteins, Department of Biochemistry, Faculty of Medicine, National Autonomous University of Mexico, Mexico City 04510, Mexico, Biomedical Cancer Research Unit, Basic Research Subdirection, National Institute of Cancer, Mexico City 14080, Mexico
Published online on: May 28, 2014 https://doi.org/10.3892/ol.2014.2195
Pages: 939-947

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Abstract

The present study aimed to analyze sera proteins in females with cervical intraepithelial neoplasia, grade III (CIN III) and in healthy control females, in order to identify a potential biomarker which detects lesions that have a greater probability of cervical transformation. The present study investigated five sera samples from females who were Human Papilloma Virus (HPV) 16+ and who had been histopathologically diagnosed with CIN III, as well as five sera samples from healthy control females who were HPV‑negative. Protein separation was performed using two‑dimensional (2D) gel electrophoresis and the proteins were stained with Colloidal Coommassie Blue. Quantitative analysis was performed using ImageMaster 2D Platinum 6.0 software. Peptide sequence identification was performed using a nano‑LC ESIMS/MS system. The proteins with the highest Mascot score were validated using western blot analysis in an additional 55 sera samples from the control and CIN III groups. The eight highest score spots that were found to be overexpressed in the CIN III sera group were identified as α‑1‑B glycoprotein (A1BG), complement component 3 (C3), a pro‑apolipoprotein, two apolipoproteins and three haptoglobins. Only A1BG and C3 were validated using western blot analysis, and the bands were compared between the two groups using densitometry analysis. The relative density of the bands of A1BG and C3 was found to be greater in all of the serum samples from the females with CIN III, compared with those of the individuals in the control group. In summary, the present study identified two proteins whose expression was elevated in females with CIN III, suggesting that they could be used as biomarkers for CIN III. However, further investigations are required in order to assess the expression of A1BG and C3 in different pre‑malignant lesions.

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1	Weiderpass E and Labrèche F: Malignant tumors of the female reproductive system. Saf Health Work. 3:166–180. 2012.
2	Ferlay J, Shin HR, Bray F, et al: Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 127:2893–2917. 2010.
3	Jemal A, Bray F, Center MM, et al: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011.
4	Bruni L, Barrionuevo-Rosas L, Serrano B, et al: Human Papillomavirus and Related Diseases Report. Mexico: http://www.hpvcentre.net/statistics/reports/MEX.pdf. Accessed March 17, 2014
5	Richart RM: Cervical intraepithelial neoplasia. Pathol Annu. 8:30–28. 1973.
6	Richart RM: A modified terminology for cervical intraepithelial neoplasia. Obstet Gynecol. 75:131–133. 1990.
7	Solomon D, Davey D, Kurman R, Moriarty A, O‘Connor D, Prey M, et al: The 2001 Bethesda System: terminology for reporting results of cervical cytology. JAMA. 287:2114–2119. 2002.
8	Syrjänen K: Histology, classification and natural history of cervical intraepithelial neoplasia (CIN). CME J Gynecol Oncol. 14:4–21. 2009.
9	Correa P: A human model of gastric carcinogenesis. Cancer Res. 48:3554–3560. 1988.
10	Lie AK, Risberg B, Borge B, Sandstad B, Delabie J, Rimala R, et al: DNA- versus RNA-based methods for human papillomavirus detection in cervical neoplasia. Gynecol Oncol. 97:908–915. 2005.
11	Wright TC Jr: Cervical cancer screening in the 21st century: is it time to retire the Pap smear? Clin Obstet Gynecol. 50:313–323. 2007.
12	Burd E: Human papillomavirus and cervical cancer. Clin Microbiol Rev. 16:1–17. 2003.
13	Snijders PJ, Heideman DA and Meijer CJ: Methods for HPV detection in exfoliated cell and tissue specimens. APMIS. 118:520–528. 2010.
14	Grubisić G, Klarić P, Jokanović L, et al: Diagnostic approach for precancerous and early invasive cancerous lesions of the uterine cervix. Coll Antropol. 33:1431–1436. 2009.
15	Cho W: Proteomics technologies and challenges. Genomics Proteomics Bioinformatics. 5:77–85. 2007.
16	Breuer EK and Murph MM: The role of proteomics in the diagnosis and treatment of women’s cancers: current trends in technology and future opportunities. Int J Proteomics. 2011:1–17. 2011.
17	Veenstra TD, Conrads TP, Hood BL, et al: Biomarkers: mining the biofluid proteome. Mol Cell Proteomics. 4:409–418. 2005.
18	Xu X and Veenstra TD: Analysis of biofluids for biomarker research. Proteomics Clin. 2:1403–1412. 2008.
19	Abdul-Rahman PS, Lim BK and 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. 28:1989–1996. 2007.
20	Barba de la Rosa AP, Lugo-Melchor OY, Briones-Cerecero EP, Chagolla-López A, de León-Rodríguez A, Santos L, et al: Analysis of human serum from women affected by cervical lesions. J Exp Ther Oncol. 7:65–72. 2008.
21	Matthews R, Azuero A, Asmellash S, et al: Usefulness of serum mass spectrometry to identify women diagnosed with higher grades of cervical intraepitelial neoplasia may differ by race. Inter J Womens Health. 3:185–192. 2011.
22	Guo X, Abliz G, Reyimu H, Zhao F, Kadeer N, Matsidik R, et al: The association of a distinct plasma proteomic profile with the cervical high-grade squamous intraepithelial lesion of Uyghur women: a 2D liquid-phase chromatography/mass spectrometry study. Biomarkers. 17:352–361. 2012.
23	Piyathilake CJ, Oelschlager DK, Meleth S, Partridge EE and Grizzle WE: Plasma protein profiles differ between women diagnosed with cervical intraepithelial neoplasia (cin) 1 and 3. Cancer Inform. 2:345–349. 2007.
24	Jeong DH, Kim HK, Prince AE, Lee DS, Kim YN, Han J and Kim KT: Plasma proteomic analysis of patients with squamous cell carcinoma of the uterine cervix. J Gynecol Oncol. 19:173–180. 2008.
25	Looj ML, Karsani SA, Rahman MA, et al: Plasma proteome analysis of cervical intraepithelial neoplasia and cervical squamous cell carcinoma. J Biosci. 34:917–925. 2009.
26	Ono A, Kumai T, Koizumi H, et al: Overexpression of heat shock protein 27 in squamous cell carcinoma of the uterine cervix: a proteomic analysis using archival formalin-fixed, paraffin-embedded tissues. Hum Pathol. 40:41–49. 2009.
27	Zhu X, Lv J, Yu L, et al: Proteomic identification of differentially-expressed proteins in squamous cervical cancer. Gynecol Oncol. 112:248–256. 2009.
28	Liu C, Pan C, Shen J, et al: Discrimination analysis of mass spectrometry proteomics for cervical detection. Med Oncol. 28(Suppl 1): S553–S559. 2011.
29	Fukushima C, Murakami A, Yoshitomi K, Sueoka K, Nawata S, Nakamura K and Sugino N: Comparative proteomic profiling in squamous cell carcinoma of the uterine cervix. Proteomics Clin Appl. 5:133–140. 2011.
30	Uleberg KE, Munk AC, Skaland I, Furlan C, van Diermen B, Gudlaugsson E, et al: A protein profile study to discriminate CIN lesions from normal cervical epithelium. Cell Oncol (Dordr). 34:443–450. 2011.
31	Uleberg KE, Munk AC, Brede C, Gudlaugsson E, van Diermen B, Skaland I, et al: Discrimination of grade 2 and 3 cervical intraepithelial neoplasia by means of analysis of water soluble proteins recovered from cervical biopsies. Proteome Sci. 9:362011.
32	Pinto A, Crum C and Hirsch M: Molecular markers of early cervical neoplasia. Diagn Histopathology (Oxf). 16:445–454. 2010.
33	Galgano MT, Castle PE, Atkins KA, et al: Using biomarkers as objective standards in the diagnosis of cervical biopsies. Am J Surg Pathol. 34:1077–1087. 2010.
34	Martin C and O‘Leary JJ: Histology of cervical intraepithelial neoplasia and the role of biomarkers. Best Pract Res Clin Obstet Gynaecol. 25:605–615. 2011.
35	Anderson NL, Esquer-Blasco R, Hofmann JP and Anderson NG: A two-dimensional gel database of rat liver proteins useful in gene regulation and drug effects studies. Electrophoresis. 12:907–930. 1991.
36	Welinder C and Ekblad L: Coomassie staining as loading control in Western blot analysis. J Proteome Res. 10:1416–1419. 2011.
37	Lörincz A: Hybrid Capture method for detection of human papillomavirus DNA in clinical specimens: a tool management of equivocal Pap smears and for population screening. J Obstet Gynaecol Res. 22:629–636. 1996.
38	Yoshikawa H, Kawana K, Kitagawa K, et al: Detection and typing of multiple genital human papillomaviruses by DNA amplification with consensus primers. Jpn J Cancer Res. 82:524–531. 1991.
39	Mishra A and Verma M: Cancer biomarkers: are we ready for the prime time? Cancers (Basel). 2:190–208. 2010.
40	Gutman S and Kessler LG: The US Food and Drug Administration perspective on cancer biomarker development. Nat Rev Cancer. 6:565–571. 2006.
41	de Visser KE, Korets LV and Coussens LM: Early neoplastic progression is complement independent. Neoplasia. 6:768–776. 2004.
42	Pio R: Control of complement activation by cancer cells and its implications in antibody-mediated cancer immunotherapy. Revisión Inmunología. 25:173–87. 2006.(In Spanish).
43	Bjørge L, Hakulinen J, Vintermyr OK, Jarva H, Jensen TS, Iversen OE and Meri S: Ascitic complement system in ovarian cancer. Br J Cancer. 92:895–905. 2005.
44	Lee IN, Chen CH, Sheu JC, Lee HS, Huang GT, Chen DS, et al: Identification of complement C3a as a candidate biomarker in human chronic hepatitis C and HCV-related hepatocellular carcinoma using a proteomics approach. Proteomics. 6:2865–2873. 2006.
45	Hanas JS, Hocker JR, Cheung JY, Larabee JL, Lerner MR, Lightfoot SA, et al: Biomarker identification in human pancreatic cancer sera. Pancreas. 36:61–69. 2008.
46	Xu G, Hou CR, Jiang HW, Xiang CQ, et al: Serum protein profiling to identify biomarkers for small renal cell carcinoma. Indian J Biochem Biophys. 47:211–218. 2010.
47	Pulay A, Füst G and Csömör A: Serum complement levels in patients with cancer of the uterine cervix before and after radiation therapy. Neoplasma. 27:211–216. 1980.
48	Ornellas P, Ornellas AA, Chinello C, Gianazza E, Mainini V, Cazzaniga M, et al: Down regulation of C3 and C4A/B complement factor fragments in plasma from patients with squamous cell carcinoma of the penis. Int Braz J Urol. 38:739–749. 2012.
49	Alfonso L, Moyses N, Alves G, Ornellas AA, Passos MR, do Oliveira LH and Cavalcanti SM: Prevalence of human papillomavirus and Epstein-Barr virus DNA in penile cancer cases from Brazil. Mem Inst Oswaldo Cruz. 107:18–23. 2012.
50	Campo MS, Graham SV, Cortese MS, Ashrafi GH, Araibi EH, Dornan ES, et al: HPV-16 E5 down-regulates expression of surface HLA class I and reduces recognition by CD8 T cells. Virology. 407:137–142. 2010.
51	Rutkowski MJ, Sughurue ME, Kane AJ, Mills SA and Parsa AT: Cancer and the complement cascade. Mol Cancer Res. 8:1453–1465. 2010.
52	Pakharukova NA, Pastushkova LKh, Moshkovskiǐ SA and Larina IM: Variability of healthy human proteome. Biomed Khim. 58:514–529. 2012.(In Russian).
53	Ishioka N, Takahashi N and Putnam FW: Amino acid sequence of human plasma alpha 1B-glycoprotein: homology to the immunoglobulin supergene family. Proc Natl Acad Sci USA. 83:2363–2367. 1986.
54	Piyaphanee N, Ma Q, Kremen O, Czech K, Greis K, Mitsnefes M, et al: Discovery and initial validation of α 1-B glycoprotein fragmentation as a differential urinary biomarker in pediatric steroid-resistant nephrotic syndrome. Proteomics Clin Appl. 5:334–342. 2011.
55	Huang HL, Stasyk T, Morandell S, Dieplinger H, Falkensammer G, Griesmacher A, et al: Biomarker discovery in breast cancer serum using 2-D differential gel electrophoresis/MALDI-TOF/TOF and date validation by routine clinical assays. Electrophoresis. 27:1641–1650. 2006.
56	Weinberg ED: The role of iron in cancer. Eur J Cancer Prev. 5:19–36. 1996.
57	Thadikkaran L, Siegenthaler MA, Crettaz D, et al: Recent advances in blood-related proteomics. Proteomics. 5:3019–3034. 2005.
58	Dowling P, Clarke C, Hennessy K, Torralbo-Lopez B, Ballot J, Crown J, et al: Analysis of acute-phase proteins, AHSG, C3, CLI, HP and SAA, reveals distinctive expression patterns associated with breast, colorectal and lung cancer. Int J Cancer. 131:911–923. 2012.
59	Jiang JT, Xu N, Zhang XY and Wu CP: Lipids changes in liver cancer. J Zhejiang Univ Sci B. 8:398–409. 2007.(In Chinese).
60	Steel LF, Shumpert D, Trotter M, Seeholzer SH, Evans AA, London WT, et al: A strategy for the comparative analysis of serum proteomes for the discovery of biomarkers for hepatocellular carcinoma. Proteomics. 3:601–609. 2003.
61	Cohen M, Yossef R, Erez T, Kugel A, Welt M, Karpasas MM, et al: Serum apolipoproteins C-I and C-III are reduced in stomach cancer patients: results from MALDI-based peptidome and immuno-based clinical assays. Plos One. 6:e145402011.
62	Pio R, Ajona D and Lambris JD: Complement inhibition in cancer therapy. Semin Immunol. 25:54–64. 2013.