Profiling of serum and tissue high abundance acute-phase proteins of patients with epithelial and germ line ovarian carcinoma

Yeng Chen,Puteri Shafinaz Abdul-Rahman,Boon-Kiong Lim,Onn Haji Hashim,Suat-Cheng Peh

doi:10.1186/1477-5956-6-20

Abstract

BackgroundAcute-phase response involves the simultaneous altered expression of serum proteins in association to inflammation, infection, injury or malignancy. Studies of the acute-phase response usually involve determination of the levels of individual acute-phase serum proteins. In the present study, the acute-phase response of patients with epithelial (EOCa) and germ-line (GOCa) ovarian carcinoma was investigated using the gel-based proteomic approach, a technique which allowed the simultaneous assessment of the levels of the acute-phase serum high abundance proteins. Data obtained were validated using ELISA and immunostaining of biopsy samples.ResultsEnhanced expression of clusterin (CLU), α1-antitrypsin, haptoglobin and leucine rich glycoprotein was detected in all patients. However, the levels of α1-antichymotrypsin (ACT) was only enhanced in EOCa patients, while patients with GOCa were typically characterized by elevated levels of ceruloplasmin but lower levels of α2-HS glycoprotein. The enhanced expression of CLU in EOCa and GOCa patients and up-regulated expression of ACT specifically in EOCa patients were confirmed by ELISA. Immunohistochemical staining of biopsy samples of EOCa and GOCa patients demonstrated correlation of the acute-phase protein expression.ConclusionPatients with EOCa and GOCa demonstrated distinctive aberrant expression of serum and tissue high abundance acute-phase proteins compared to negative control women.

Highlights

Acute-phase response involves the simultaneous altered expression of serum proteins in association to inflammation, infection, injury or malignancy
Serum Protein Profiles When unfractionated whole sera of negative control women unaffected by cancer (n = 30) were subjected to 2DE and silver staining under the resolving conditions adopted in the present study, the high abundance proteins that were detected include albumin, the heavy and light chains of IgA, IgG and IgM, two groups of CLU (CLU and CLU2), α2-HS glycoprotein (AHS), ABG, AAT and its fragment Fragment of AAT (AATf), ACT, CPL, β chains of HAP (HAP), leucine rich glycoprotein (LRG) and hemopexin (HPX) (Figure 1, panel A)
By using 2-DE and image analysis, we have demonstrated the alteration of serum high abundance proteins expression involving higher expression of CLU, AAT, AATf, LRG, HAP and Cleaved β chains of HAP (HAPc) in sera of both cohorts of patients with epithelial ovarian carcinoma (EOCa) and germ line ovarian carcinoma (GOCa)

Summary

Introduction

Acute-phase response involves the simultaneous altered expression of serum proteins in association to inflammation, infection, injury or malignancy. The expression of serum proteins can be analysed concurrently by using the gel-based proteomic technology This is appropriate for studying the acute-phase response, which involves the simultaneous altered expression of serum proteins in association to inflammation, infection, injury or cancer [1]. Many of the proteomic studies on serum or plasma have been performed using samples that were depleted of albumin and/or immunoglobulins in order to analyze serum proteins of lower abundance [2,3,4]. A number of serum proteins including those that have been used clinically or experimentally have been demonstrated to adhere strongly to albumin and immunoglobulins [5] These serum proteins were removed in experiments involving depletion of the high abundance proteins, and may affect interpretation of the results. IgG, IgM, transferrin, fibrinogen, haptoglobin (HAP) and α1-antitrypsin (AAT) from rat plasma leads to the unmasking of only a few proteins and was still far from being able to detect the low abundance proteins [6]

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Discussion

Conclusion