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Urinary endogenous peptides as biomarkers for prostate cancer

ABSTRACT: Prostate cancer (PCa) is one of the most prevalent cancer types in men worldwide. However, the main diagnostic tests available for PCa have limitations and need biopsy for histopathological confirmation of the disease. The prostate-specific antigen (PSA) is the main biomarker used for PCa early detection, but an elevated serum concentration is not cancer-specific. Therefore, there is a need for discovery of new non-invasive biomarkers that can accurately diagnose PCa. Here, we used trichloroacetic acid-induced protein precipitation and liquid chromatography-mass spectrometry to profile endogenous peptides in urine samples from patients with PCa (n = 33), benign prostatic hyperplasia (n = 25), and healthy individuals (n = 28). Receiver operating characteristic (ROC) curves were performed to evaluate the diagnostic performance of urinary peptides. In addition, proteasix tool was used for in silico prediction of protease cleavage sites. We found five urinary peptides derived from uromodulin significantly altered between the study groups, all of which were less abundant in the PCa group. In addition, urinary peptides outperformed PSA in discriminating between malignant and benign prostate conditions (AUC = 0.847), showing high sensitivity (81.82%) and specificity (88%). Overall, our study allowed the identification of urinary peptides with potential for use as non-invasive biomarkers in PCa diagnosis.

INSTRUMENT(S): Q-Tof Ultima

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Urine

DISEASE(S): Prostate Adenocarcinoma

SUBMITTER: Cristine Dutra

LAB HEAD: Karina Mariante Monteiro

PROVIDER: PXD037031 | Pride | 2022-10-25

REPOSITORIES: Pride

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			Action	DRS
	20190910_KMM_Cris_01_IA_final_peptide.csv	Csv
	20190910_KMM_Cris_01_cont1.raw.zip	Raw
	20190910_KMM_Cris_02_IA_final_peptide.csv	Csv
	20190910_KMM_Cris_02_cont1.raw.zip	Raw
	20190910_KMM_Cris_03_IA_final_peptide.csv	Csv

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Project description:Predicting Outcomes of Prostate Cancer Immunotherapyby Personalized Mathematical Models Natalie Kronik1¤, Yuri Kogan1, Moran Elishmereni1, Karin Halevi-Tobias1, Stanimir Vuk-Pavlovic ́2.,Zvia Agur1*.1Institute for Medical BioMathematics, Bene Ataroth, Israel,2College of Medicine, Mayo Clinic, Rochester, Minnesota, United States of America Abstract Background:Therapeutic vaccination against disseminated prostate cancer (PCa) is partially effective in some PCa patients.We hypothesized that the efficacy of treatment will be enhanced by individualized vaccination regimens tailored by simplemathematical models.Methodology/Principal Findings:We developed a general mathematical model encompassing the basic interactions of avaccine, immune system and PCa cells, and validated it by the results of a clinical trial testing an allogeneic PCa whole-cellvaccine. For model validation in the absence of any other pertinent marker, we used the clinically measured changes inprostate-specific antigen (PSA) levels as a correlate of tumor burden. Up to 26 PSA levels measured per patient were dividedinto each patient’s training set and his validation set. The training set, used for model personalization, contained thepatient’s initial sequence of PSA levels; the validation set contained his subsequent PSA data points. Personalized modelswere simulated to predict changes in tumor burden and PSA levels and predictions were compared to the validation set.The model accurately predicted PSA levels over the entire measured period in 12 of the 15 vaccination-responsive patients(the coefficient of determination between the predicted and observed PSA values wasR2= 0.972). The model could notaccount for the inconsistent changes in PSA levels in 3 of the 15 responsive patients at the end of treatment. Each validatedpersonalized model was simulated under many hypothetical immunotherapy protocols to suggest alternative vaccinationregimens. Personalized regimens predicted to enhance the effects of therapy differed among the patients.Conclusions/Significance:Using a few initial measurements, we constructed robust patient-specific models of PCaimmunotherapy, which were retrospectively validated by clinical trial results. Our results emphasize the potential value andfeasibility of individualized model-suggested immunotherapy protocols.

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Urinary endogenous peptides as biomarkers for prostate cancer

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