Proteomics-based identification of α1-antitrypsin and haptoglobin precursors as novel serum markers in infiltrating ductal breast carcinomas

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• 作者：Bechr Hamrita ; Karim Chahed ; Mounir Trimeche ; Christelle Lemaitre Guillier ; Philippe Hammann ; Anouar Chaï ; eb ; Sadok Korbi ; Lotfi Chouchane
• 关键词：Infiltrating ductal breast carcinomas ; Tumor marker ; Serological proteome analysis
• 刊名：Clinica Chimica Acta
• 出版年：2009
• 出版时间：27 June 2009
• 年：2009
• 卷：404
• 期：2
• 页码：111-118
• 全文大小：700 K

文摘

Background

The identification of pathological markers of breast cancer for either diagnosis, treatment response or for survival is of critical importance.

Methods

Serum protein profiling using 2-DE separations coupled to matrix-assisted laser desorption ionization mass spectrometry has been used to explore protein alterations in patients with infiltrating ductal breast carcinomas (IDCA). Sera from 39 breast cancer patients and 40 healthy controls were selected for screening study using 2-DE combined with MS. The protein expression patterns obtained after the depletion of high abundance proteins was determined by coomassie blue G-250 stain after 2-DE electrophoresis.

Results

Six proteins that expressed differentially in the IDCA group were found. The expression levels of four isoforms corresponding to haptoglobin precursor and two isoforms of α1-antitrypsin precursor (α1-AT) were upregulated in sera from breast cancer patients. There was an increased expression of both proteins in the sera of patients with various tumor stages (I, II, III) in comparison to healthy women. Applying immunohistochemistry, we further validated α1-AT immunoreactivity in 51 formalin-fixed paraffin-embedded sections of breast tumors. Enhanced expression of α1-AT like activity has been found in IDCA breast tumors, as well as, in different histological types of breast cancer. No significant association has been found with lymph node occurrence, while in high tumor categories a tendency to an increased expression of α1-AT has been found, thereby suggesting a possible role of this protein in tumor growth.

Conclusions

These proteins may constitute new and useful markers of breast cancer that offer a clue to a better understanding of inflammatory pathways and carcinogenesis events linked to breast cancer progression.