= Emerging. More than 5 years before clinical availability. (26.62%)
= Expected to be clinically available in 1 to 4 years. (38.91%)
= Clinically available now. (34.47%)
MSACL 2020 US : Spivia

MSACL 2020 US Abstract

Topic: Proteomics

Podium Presentation in Room 5 on Wednesday at 9:00 (Chair: Stephen Pennington)

Quantification of Fully and Partially Acetylated HMGB1 Protein in the Serum and Pleural Effusion of Mesothelioma and Non-mesothelioma Individuals

Weston Spivia (Presenter)
Cedars Sinai Medical Center

Presenter Bio(s): Weston Spivia, MSc. has extensive experience in applying mass spectrometry to clinically relevant research questions. His work involves both preparative and analytical method development for the analysis of proteins, metabolites, and lipids from complex biological matrices such as plasma.

Authors: Weston R Spivia (1), (1) Angela McArdle, (1) Justyna Fert-Bober, (3) Harvey Pass, (2) Haining Yang, (2) Michele Carbone, Jennifer Van Eyk
(1) Cedars Sinai Medical Center, Los Angeles, CA, (2) University of Hawaii, Manoa, HI, (3) New York University, New York, NY

Abstract

Introduction: Malignant mesothelioma (MM) is an aggressive cancer associated with exposure to asbestos and other carcinogenic mineral fibers. Recently it has been reported that High Mobility Group Box 1 (HMGB1), a damage-associated molecular pattern protein, contributes to MM. HMGB1 cellular localization and its secretion is regulated by acetylation of lysine residues located within its two nuclear localization signals sequences. Non-acetylated HMGB1 is primarily localized in the nucleus, where it binds to chromatin and stabilizes nucleosomes and alters gene transcription. Hyper-acetylated HMGB1 is sequestered into the cytoplasm followed by active secretion into the extra-cellular space where can act as a paracrine/autocrine factor.

Objective: The primary objective of this study was to discriminate MM from other non-MM cancers based on the amount of the hyper-acetylated HMGB1 secreted by MM cells in serum and pleural effusion samples.

Methods: The reliable measurement and quantification of hyper-acetylated HMGB1 in serum is technologically formidable. Potential technical restrictions are the small molecular weight of HMGB1, high basic charge, and prospective post-translational modifications. To overcome the limitation we developed a targeted MS-based method, parallel reaction monitoring (PRM), to quantify unmodified, partially acetylated, and hyper-acetylated HMGB1 in patient serum and matched pleural effusion samples.

Results: Serum and pleural effusion samples from 52 individuals diagnosed with MM or non-MM lung cancer were analyzed by a PRM-MS method. The concentration of total and hyper-acetylated HMGB1 in serum and pleural effusion samples were quantified using internal standard peptides. Lower limit of detection, lower limit of quantification as well as Intra- and interday precision were calculated for all samples based on the calibration curves. Informative patterns of fully and partially hyper-acetylated proteoforms of HMGB1 between the two nuclear translocation signals were observed in the pleural effusion samples but not in serum samples.

Conclusion: Our method can discriminate MM from non-MM patients with high sensitivity, specificity and accuracy based on the different proteoforms of hyper-acetylated HMGB1.


Financial Disclosure

DescriptionY/NSource
GrantsyesCedars Sinai
SalaryyesCedars Sinai
Board Memberno
Stockno
Expensesno
IP Royaltyno

Planning to mention or discuss specific products or technology of the company(ies) listed above:

no