Evaluation of Haptoglobin and Its Proteoforms as Glioblastoma Markers

Abstract

Haptoglobin (Hp) is a blood plasma glycoprotein that plays a critical role in tissue protection and the prevention of oxidative damage. Haptoglobin is an acute-phase protein, its concentration in plasma changes in pathology, and the test for its concentration is part of normal clinical practice. Haptoglobin is a conservative protein and is the subject of research as a potential biomarker of many diseases, including malignant neoplasms. The Human Hp gene is polymorphic and controls the synthesis of three major phenotypes—homozygous Hp1-1 and Hp2-2, and heterozygous Hp2-1, determined by a combination of allelic variants that are inherited. Numerous studies indicate that the phenotype of haptoglobin can be used to judge the individual’s predisposition to various diseases. In addition, Hp undergoes various post-translational modifications (PTMs). Glioblastoma multiform (GBM) is the most malignant primary brain tumor. In our study, we have analyzed the state of Hp proteoforms in plasma and cells using 1D (SDS-PAGE) and 2D electrophoresis (2DE) with the following mass spectrometry (LC ES-MS/MS) or Western blotting. We found that the levels of α2- and β-chain proteoforms are up-regulated in the plasma of GBM patients. An unprocessed form of Hp2-2 (PreHp2-2, zonulin) with unusual biophysical parameters (pI/Mw) was also detected in the plasma of GBM patients and glioblastoma cells. Altogether, this data shows the possibility to use proteoforms of haptoglobin as a potential GBM-specific plasma biomarker.

A New Thinking: Deciphering the Aberrance and Clinical Implication of IGF Axis Regulation Pattern in Clear Cell Renal Cell Carcinoma

“…A recent report found that SCX regulated Twist1 and Snai1 expression in the epithelialto-mesenchymal transition (45). HP was regarding as a molecular biomarker in non-small cell lung cancer and glioblastoma (46,47). We also verified the high accuracy of the RCIP4 risk model both in the TCGA-ccRCC and JAPAN-KIRC database.…”

Prohaptoglobin inhibits the transforming growth factor-β-induced epithelial-to-mesenchymal transition in vitro by increasing Smad1/5 activation and suppressing the Smad2/3 signaling pathway in SK-Hep1 liver cancer cells

“…Three major phenotypes according to gene polymorphisms (Hp1-1, Hp2-1, and Hp2-2), unprocessed precursors (proHp1 and proHp2), and unusually glycosylated Hp (especially fucosylated Hp) have been reported and they play diverse roles in inflammation, diabetic vascular disease, angiogenesis, and malignant tumors [ 19 , 20 , 24 ]. The plasma Hp level, Hp expression in tumor cells, and Hp fucosylation are reportedly related to cancer development and have been suggested to be candidate biomarkers of various cancers including HCC, colorectal cancer, pancreatic cancer, and glioblastoma [ 20 , 33 , 34 ]. In addition, a preliminary report showed an association of tissue Hp expression and the EMT in buccal cancer [ 35 ].…”

Clinical Significance of Serum Haptoglobin and Protein Disulfide-Isomerase A3 in the Screening, Diagnosis, and Staging of Colorectal Cancer

“…Previous studies demonstrate that HP expressions are higher in the serum of patients with liver cancer, lung cancer, ovarian cancer, or other cancers than in the serum of healthy subjects. Furthermore, HP expressions combined with other serum markers, would be of reference value to the early diagnosis of relevant cancers and of some guiding significance in terms of treatment and prognosis ( Naryzhny et al, 2021 ).…”