Bladder cancer biomarker proteins
Inventors
Garin, Jerome • Masselon, Christophe • Vlahou, Antonia • MAKRYDAKIS, Manousos • ZOIDAKIS, Ieronimos • Domon, Bruno • Duriez, Elodie • KAMOUN, Aurelie • Radvanyi, Francois • Allory, Yves • MALATS RIERA, Nuria • MARQUEZ CID, Mirari • COURT, Magali
Assignees
Fundacion Centro Nacional De Investigaciones Oncologicas Carlos Iii Cnio • Polyquant GmbH • Fundacion Centro Nacional De Investigaciones Oncologicas Carlos Iii Cnio • Assistance Publique Hopitaux de Paris APHP • Institut Curie • Commissariat a lEnergie Atomique et aux Energies Alternatives CEA • BIOMEDICAL RESEARCH FOUNDATION OF ACADEMY OF ATHENS • Luxembourg Institute of Health LIH
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Publication Number
US-11536724-B2
Publication Date
2022-12-27
Expiration Date
Abstract
The invention relates to a collection of signature peptides representing at least 10 proteins for use in cancer diagnosis and/or prognosis, to an artificial protein comprising signature peptides representing at least 10 proteins and to a nucleic acid construct encoding for such an artificial protein. The invention further relates to a collection of at least 10 proteins for use in cancer diagnosis and/or prognosis. Additionally, the invention relates to a method for cancer diagnosis and/or prognosis comprising the step of analyzing at least 10 proteins in a urine sample of a subject. Finally, the invention relates to an immunoassay product comprising antibodies for detecting at least 10 proteins.
Core Innovation
The disclosure provides biomarker panels for bladder/urothelial urinary tract cancer using signature peptides derived from proteins, where each signature peptide represents a protein-unique proteotypic peptide. Signature peptides are related to targeted mass spectrometry readouts, including selected reaction monitoring (SRM), time-scheduled SRM, and parallel reaction monitoring (PRM), for detecting and quantifying target proteins from urine sample(s). The signature peptide concept is explicitly defined as protein-unique proteotypic peptides that enable consistent protein measurements across peptide readouts.
The document links the measured protein panels to clinical occurrence and risk stratification, describing distinct protein panels associated with initial occurrence of bladder cancer and with recurrence/progression risk. It reports targeted proteomics workflows involving SRM/PRM screening of candidate bladder-cancer proteins using incident and prevalent/recurrence cohorts with biopsy-confirmed statuses, together with reduction to consistent quantitative peptide/protein measurements and data-quality filtering using transition consistency and Cronbach’s alpha, with normalization to reduce peptide-dependent bias.
The disclosure also provides protein detection products and artificial protein constructs composed of signature peptides. An artificial protein is described as comprising at least 10 signature peptides representing at least 10 proteins, where the signature peptides consist of sequences selected from a provided group of SEQ ID NOs, and each signature peptide represents a single protein. Artificial protein embodiments are further described through construction of artificial proteins and nucleic acid/QconCAT concatenates that join signature peptides separated by cleavage sequences, including optional tags, and immunoassay product embodiments using antibodies to detect at least 10 proteins.
Claims Coverage
The provided claim content contains independent claims directed to an artificial protein comprising at least 10 signature peptides mapped to selected human proteins. The inventive features focus on the minimum number of signature peptides, their selection from enumerated sequences, and in one claim a 1:1 stoichiometric ratio for each signature peptide.
Artificial protein with at least 10 signature peptides representing selected human proteins by enumerated peptide sequences
An artificial protein comprising at least 10 signature peptides, where the signature peptides consist of sequences selected from a group consisting of enumerated sequences (SEQ ID NOs) representing proteins selected from the group consisting of A1AT_HUMAN, A2MG_HUMAN, ALDOA_HUMAN, DPP4_HUMAN, EGF_HUMAN, ITIH2_HUMAN, LG3BP_HUMAN, PIP_HUMAN, SORL_HUMAN, TRFE_HUMAN, VTDB_HUMAN, ES8L2_HUMAN, HBA_HUMAN, HBB_HUMAN, HPT_HUMAN, K1C17_HUMAN, PRDX4_HUMAN, RAI3_HUMAN, RAP2A_HUMAN, and RAP2B_HUMAN, wherein each signature peptide represents a single protein.
1:1 stoichiometric ratio for each signature peptide in the artificial protein
The artificial protein comprises each signature peptide at a 1:1 stoichiometric ratio.
Artificial protein specified by at least 10 enumerated signature peptide sequences
An artificial protein comprising at least 10 signature peptides, wherein the signature peptides consist of sequences selected from the group consisting of the enumerated SEQ ID NOs and corresponding sequence strings provided in the claim.
Overall, the claim coverage is directed to an artificial protein defined by at least 10 signature peptides with sequences selected from an enumerated set, where each peptide corresponds to a single protein from the listed group. One independent claim additionally requires 1:1 stoichiometry for all included signature peptides.
Stated Advantages
Consistent protein measurements across peptide readouts.
Normalization to reduce peptide-dependent bias.
Documented Applications
Detection and quantification of target proteins from urine sample(s).
Bladder/urothelial urinary tract cancer biomarker panels associated with initial occurrence, recurrence, and progression risk.
Immunoassay product embodiments using antibodies to detect at least 10 proteins.
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