Trapping of Human Hemoglobin by Haptoglobin: Molecular Mechanisms and Clinical Applications

Ratanasopa, Khuanpiroon; Chakane, Sandeep; Ilyas, Muhammad; Nantasenamat, Chanin; Bülow, Leif

doi:10.1089/ars.2012.4878

Cited by 39 publications

(31 citation statements)

References 95 publications

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“…29 It also has catalytic and antibacterial capacities in controlling the acute-phase response and plays a role as a natural antagonist for receptor-ligand activation in the immune system. 30,31 Haptoglobin is a highly sialylated glycoprotein with four N-glycosylation sites at Asn 184, 207, 211, and 241. 32,33 It has gained considerable attention because of its potential as a signature molecule to display aberrant glycosylation in inflammatory disorders (e.g., liver cirrhosis, pancreatitis) and various types of cancer (e.g., of colon, lung, liver, prostate and pancreas).…”

Section: Introductionmentioning

confidence: 99%

Glycomic profiling of targeted serum haptoglobin for gastric cancer using nano LC/MS and LC/MS/MS

et al. 2016

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Gastric cancer has one of the highest cancer mortality rates worldwide, largely because of difficulties in early-stage detection. Aberrant glycosylation in serum proteins is associated with many human diseases including inflammation and various types of cancer. Serum-based global glycan profiling using mass spectrometry has been explored and has already led to several potential glycan markers for several disease states. However, localization of the aberrant glycosylation is desirable in order to improve the specificity and sensitivity for clinical use. Here, we combined protein-specific immunoaffinity purification, glycan release, and MS analysis to examine haptoglobin glycosylation of gastric cancer patients for glyco-markers. Age- and sex-matched 60 serum samples (30 cancer patients and 30 healthy controls) were used to profile and quantify haptoglobin N-glycans. A T-test based statistical analysis was performed to identify potential glyco-markers for gastric cancer. Interestingly, abundances of several tri- and tetra-antennary fucosylated N-glycans were increased in gastric cancer patients. Additionally, structural analysis via LC/MS/MS indicated that the fucosylated complex type N-glycans were primarily decorated with antenna fucose, which can be categorized as sialyl-Le or sialyl-Le type structures. This platform demonstrates quantitative, structure-specific profiling of haptoglobin glycosylation for the purposes of biomarker discovery for gastric cancer.

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Section: Introductionmentioning

confidence: 99%

Glycomic profiling of targeted serum haptoglobin for gastric cancer using nano LC/MS and LC/MS/MS

et al. 2016

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“…Hp, a major acute-phase glycoprotein comprising 0.4–2.6% of total blood proteins, consists of two α- and two β-subunits whose glycosylation level changes in various types of cancer and inflammation [8, 9]. Hp is a highly sialylated glycoprotein with four N-glycosylation sites in β-chain at Asn 184, 207, 211, and 241 in β-chain [10]. It has been demonstrated that the glycosylated Hp is resulted directly from cancer itself rather than secondary to cancer-induced inflammation [11].…”

Section: Introductionmentioning

confidence: 99%

Direct analysis of aberrant glycosylation on haptoglobin in patients with gastric cancer

Kim

Lee²,

Choi³

et al. 2016

Oncotarget

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Based on our previous studies, differential analysis of N-glycan expression bound on serum haptoglobin reveals the quantitative variation on gastric cancer patients. In this prospective case-control study, we explore the clinically relevant glycan markers for gastric cancer diagnosis. Serum samples were collected from patients with gastric cancer (n = 44) and healthy control (n = 44). N-glycans alteration was monitored by intact analysis of Hp using liquid chromatography–mass spectrometry followed by immunoaffinity purification with the serum samples. Intensity and frequency markers were defined depending on the mass spectrometry data analysis. Multiple markers were found with high diagnostic efficacy. As intensity markers (I-marker), six markers were discovered with the AUC > 0.8. The high efficiency markers exhibited AUC of 0.93 with a specificity of 86% when the sensitivity was set to 95%. We additionally established frequency marker (f-marker) panels based on the tendency of high N-glycan expression. The AUC to conclude patients and control group were 0.82 and 0.79, respectively. This study suggested that N-glycan variation of serum haptoglobin were associated with patients with gastric cancer and might be a promising marker for the cancer screening.

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“…In humans, Hp has a genetic polymorphism that leads to expression of three primary Hp phenotypes that share a common Hb-binding b-chain, yet differ in their a-chain composition (34,42). Hp phenotype 1-1 expresses a smaller a-chain (a1), which can form only one disulfide bond to one other a-b subunit.…”

Section: Introductionmentioning

confidence: 99%

Human Hp1-1 and Hp2-2 Phenotype-Specific Haptoglobin Therapeutics Are Both Effective In Vitro and in Guinea Pigs to Attenuate Hemoglobin Toxicity

Lipiski

Deuel

Baek

et al. 2013

Antioxidants & Redox Signaling

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Trapping of Human Hemoglobin by Haptoglobin: Molecular Mechanisms and Clinical Applications

Abstract: A detailed analysis of the influence of Hp glycosylation will be instrumental to generate a deeper understanding of its biological function. Several pathological conditions also modify the glycan compositions allowing Hp to be potentially used as a marker protein for these disorders.

Cited by 39 publications

References 95 publications

Glycomic profiling of targeted serum haptoglobin for gastric cancer using nano LC/MS and LC/MS/MS

Glycomic profiling of targeted serum haptoglobin for gastric cancer using nano LC/MS and LC/MS/MS

Direct analysis of aberrant glycosylation on haptoglobin in patients with gastric cancer

Human Hp1-1 and Hp2-2 Phenotype-Specific Haptoglobin Therapeutics Are Both Effective In Vitro and in Guinea Pigs to Attenuate Hemoglobin Toxicity

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