Sains Malaysiana 53(8)(2024): 1749-1765

http://doi.org/10.17576/jsm-2024-5308-03

 

Proteomic Profiling of Serum of Women with BI-RADS 1 to 5: Identification of Potential Complementary Biomarkers for Early Detection of Breast Cancer

(Pemprofilan Proteomik Serum Wanita dengan BI-RADS 1 hingga 5: Pengenalpastian Penanda Bio Pelengkap Berpotensi untuk Pengesanan Awal Kanser Payudara)

 

JAIME JACQUELINE JAYAPALAN1,2,*, CHRISTINA JANE VELLAN1, TANIA ISLAM3, NUR AISHAH MOHD TAIB3 & KARUTHAN CHINNA4

 

1Department of Molecular Medicine, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia

2Universiti Malaya Centre for Proteomics Research (UMCPR), Universiti Malaya, 50603 Kuala Lumpur, Malaysia

3Department of Surgery, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia

4Faculty of Business and Management, UCSI University, Cheras, 56100 Kuala Lumpur, Malaysia

 

Diserahkan: 20 Februari 2024/Diterima: 26 Jun 2024

 

Abstract

Mammography remains the gold standard for the screening of breast cancer (BrCa) despite its shortcomings. Cancer antigen 15-3, an FDA-approved biomarker, is most useful as a treatment response and recurrence monitoring tool rather than for early detection of BrCa. Given this, we aimed to screen for potential complementary diagnostic protein biomarkers in the serum of women with BI-RADS 1 to 5. Individual neat sera of women with BI-RADS 1 to 5 (N = 33) were subjected to two-dimensional electrophoresis (2-DE) for the separation of proteins. Comparative analysis of the 2-DE silver-stained gel images was performed using Progenesis SameSpots software. The identification of protein spots of interest was determined following tandem MS/MS analysis and database search using either MASCOT or X! Tandem Vengeance search engines. Data are available via ProteomeXchange with the identifier PXD040427. The Bioinformatics tools of The Database for Annotation, Visualization, and Integrated Discovery were used for the functional annotation of the proteins of altered abundance. A total of 8 non-redundant proteins including albumin, apolipoprotein A-I, apolipoprotein A-II, clusterin, complement C3, immunoglobulin kappa constant, kininogen-1, and leucine-rich alpha-2 glycoprotein were found significantly overexpressed in the sera of women with BI-RADS 4 and/or 5 (p < 0.01, FC ≥ 2). Functional annotation of the significantly differentially expressed proteins showed their possible roles in the development of BrCa. The identified protein signatures are potential biomarkers for use in complement with mammography for improved detection of BrCa at an early stage.

 

Keywords: BI-RADS; biomaker; breast cancer; early detection; mass spectrometry; two-dimensional electrophoresis

 

 

Abstrak

Mamografi tetap dianggap sebagai piawaian emas dalam saringan kanser payudara (BrCa) walaupun terdapat beberapa kelemahan. Antigen kanser 15-3 yang diluluskan oleh FDA lebih berguna sebagai alat pemantauan tindak balas rawatan dan pengesan kanser berulang daripada untuk pengesanan awal BrCa. Oleh itu, kajian ini bertujuan untuk menyaring dan mengenal pasti penanda protein diagnostik yang mungkin menjadi pelengkap dalam serum wanita yang tergolong dalam kategori BI-RADS 1 hingga 5. Serum individu wanita tersebut telah diuji menggunakan teknik elektroforesis dua dimensi (2-DE) untuk memisahkan protein (N = 33). Analisis imej gel 2-DE dilakukan dengan menggunakan perisian Progenesis SameSpots. Pengenalpastian tompok protein yang berkaitan dilakukan melalui analisis spektrometri jisim berganda dan pencarian dalam pangkalan data menggunakan enjin carian MASCOT atau X! Tandem Vengeance. Maklumat mengenai data kajian boleh  didapati melalui repositori ProteomeXchange dengan kod pengenalan PXD040427. Alat Bioinformatik Pangkalan Data untuk Anotasi, Visualisasi dan Penemuan Bersepadu (DAVID) telah digunakan untuk anotasi fungsi protein yang mempunyai kelimpahan yang berbeza. Sejumlah 8 protein termasuk albumin, apolipoprotein A-I, apolipoprotein A-II, clusterin, complement C3, immunoglobulin kappa constant, kininogen-1 dan leucine-rich alpha-2 glycoprotein didapati meningkat secara signifikan dalam serum wanita yang tergolong dalam kategori BI-RADS 4 dan/atau 5 (p < 0.01, FC ≥ 2). Anotasi fungsi protein ini menunjukkan keterlibatan potensi mereka dalam proses perkembangan BrCa. Penemuan protein ini menonjolkan potensi sebagai penanda bio tambahan untuk digunakan bersama mammografi bagi meningkatkan keupayaan pengesanan BrCa pada peringkat awal.

 

Kata kunci: BI-RADS; elektroforesis dua dimensi; kanser payudara; penanda bio; pengesanan awal; spektrometri jisim

 

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*Pengarang untuk surat-menyurat; email: jaime_jacklyn@um.edu.my

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

   

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