Haptoglobin Polymorphisms and Fucosylation Change: Possible Influence of Variation on the Identified Lung Cancer-Relevant Biomarkers

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Author(s): Kongsak Boonyapranai*, Sakaewan Ounjaijean, Kanokwan Kulprachakarn, Laddawan Potpromanee, Miles Chih-Ming Chen, Hsien-Yu Tsai, Shui-Tien Chen

Journal Name: Current Proteomics

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Background: Haptoglobin (Hp), an acute-phase protein, is known as a potential diagnostic biomarker in human diseases. Two alleles of Hp (Hp1 and Hp2) exist in humans allowing three phenotypes (Hp1-1, Hp2-1, and Hp2-2), which influence the biophysical and biological properties of Hp.

Objective: This work aimed to investigate the variation of serum level and fucosylation change among Hp phenotypes in pa-tients with lung cancer compared to healthy donors.

Method: 44 patients with lung cancer and 26 healthy blood donors who lived in the Northern-Thailand region were investi-gated by glycoproteomic procedure.

Results: The phenotypic distribution of the Hp (Hp1-1:Hp2-1:Hp2-2) in healthy donors were 0.04:0.38:0.58, while the pa-tient group were 0.09:0.52:0.39. The Hp1 allele frequency of the patients with lung cancer (0.34) was higher than the healthy donor (0.23). Glycoprotein blotting technique represented that the level of serum Hp and its fucosylation were sig-nificantly higher among lung cancer patients compared to those of the healthy donors. However, a downward trend in the fucosylation level from Hp1-1 to Hp2-1, Hp2-2, was seen in the patient group, but varying in the serum Hp level. An N-linked glycan was enzymatically released from discrete Hp multimers of Hp2-1 and Hp2-2 samples. Analysis of glycan pro-filing by MALDI-TOF-MS showed that reduction of the fucosylated glycan was associated with the size of Hp multimers, resulting in the lower level of fucosylation in Hp2-1 and Hp2-2, respectively.

Conclusion: Our finding demonstrates that the Hp phenotype is a dependent risk factor for lung cancer and should be incor-porated into further clinical and biochemical investigations of diseases, including lung cancer.

Keywords: Haptoglobin, Phenotype, Fucosylation change, Lung cancer

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(E-pub Ahead of Print)
DOI: 10.2174/1570164617666200817115006
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