PXD024448

PXD024448 is an original dataset announced via ProteomeXchange.

Title	Novel potentially clinically valuable protein markers of androgen activity in humans
Description	Background Testosterone (T) is the main androgen playing a crucial role in regulating the function of both reproductive and non-reproductive organs. Current methods for assessing T levels in humans do not reflect the biological androgenic activity (BAA), which may be important for example in the diagnosis of hypogonadism and clarifying pathogenetic mechanisms linking androgen deficiency to various comorbidities. In this study, we aimed to identify new protein markers of BAA in humans and test their predictive value in relation to some androgen deficiency linked pathologies. Methods and Findings Plasma samples (n=90) from 30 healthy chemically castrated young volunteer males (19-32 years) were collected at three different time points: baseline – prior to treatment with GnRH antagonist), three weeks after GnRH antagonist treatment, and at the end of the study, two weeks thereafter. Following the second blood sampling, all men were supplemented with 1000 mg T undecanoate. The samples were analysed by mass spectrometry-based proteomics. A total of 676 proteins were identified among which expression of 46 was statistically significantly associated with T concentration (p<0.05, ANOVA paired). Based on ROC-analysis, 3 candidate proteins were selected, 4-hydroxyphenylpyruvate dioxygenase (4HPPD), insulin-like growth factor-binding protein 6 (IGFBP6) and fructose-bisphosphate aldolase (ALDOB). Together with a mathematically calculated variable (MMA: Multi-Marker Algorithm), based on the combination of 4HPPD and IGFBP6 values, their predictive value in relation to low T levels and cardio-metabolic risk factors was tested in 75 males suffering from infertility, 32-43 years of age. Of these males, four were diagnosed with type 2-diabetes and 14 with the metabolic syndrome. Clinical chemistry data regarding cardio-metabolic parameters, bone mineral density and androgen receptor CAG repeat lengths were assessed. The three proteins significantly distinguished between low (< 8 nmol/L) and normal (> 12 nmol/L) morning fasting T (AUC: 0.70-0.77). The MMA had an even higher accuracy (AUC=0.80) in identifying subjects with low T. 4HPPD, ALDOB and MMA showed higher accuracy than T (AUC=0.85-0.92 vs. AUC=0.55; p<.001) in identifying infertile patients with type 2 diabetes mellitus and metabolic syndrome (AUC=0.74-0.78 vs. AUC=0.56; p<0.05). These markers also showed higher AUC than T in predicting adverse cardiovascular risk lipid profile and insulin resistance patients but the differences were not statistically significant. 4HPPD and MMA distinguished patients with low bone density (z-score in DEXA scan < -1), but no difference was observed when comparing with AUC for T,. The androgenic dependence of 4HPPD and ALDOB were confirmed by finding statistically significant lower levels of these markers in men with androgen CAG repeat lengths < 21 (p=0.002) and >22 (p=0.038) as compared to those with CAG of 21-22. No statistical significances were found for IGFBP6. Conclusions 4HPPD and ALDOB were identified as potential biomarkers for diagnosis of male hypogonadism and in identifying subjects at high risk of some of its clinical sequelae. More extensive testing should be carried out in order to elucidate their usefulness in clinical assessment of androgenic activity, not only in adult males but also in women and in pre-pubertal boys.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:52:42.213.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Indira Pla Parada
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	TSQ Quantiva; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-03-01 10:02:15	ID requested
1	2022-04-07 04:17:34	announced
⏵ 2	2023-11-14 08:52:42	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: testosterone deficiency,proteomics, androgen activity, biomarkers

Johan Malm
contact affiliation	Professor at the Section for Clinical Chemistry, Department of Translational Medicine, Lund University. Sweden
contact email	johan.malm@med.lu.se
lab head
Indira Pla Parada
contact affiliation	Lund university
contact email	indira.pla_parada@med.lu.se
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD024448
     1. Label: PRIDE project
     2. Name: Novel potentially clinically valuable protein markers of androgen activity in humans