Dataset Information

Use of data-independent acquisition mass spectrometry to identify an objective serum indicator of the need for osteoporotic therapeutic intervention

ABSTRACT: Osteoporosis is characterized by weakened bone microstructure and loss of bone mass. Current diagnostic criteria for osteoporosis are based on the T-score, which is a measure of bone mineral density. However, osteoporotic fragility fractures can occur regardless of the T-score, underscoring the need for additional criteria for the early detection of patients at fracture risk. To identify indicators of reduced bone strength, we performed serum proteomic analysis using data-independent acquisition mass spectrometry with serum samples from two patient groups, one with osteoporosis but no fractures and the other with osteopenia and fragility fractures. Collective evaluation of the results identified six serum proteins that changed to a similar extent in both patient groups compared with controls. Of these, extracellular matrix protein 1 (ECM1), which contributes to bone formation, showed the most significant increase in serum levels in both patient groups. An ELISA-based assay suggested that ECM1 could serve as a serum indicator of the need for therapeutic intervention; however, further prospective studies with a larger sample size are necessary to confirm these results. The present findings may contribute to the provision of early and appropriate therapeutic strategies for patients at risk of osteoporotic fractures.

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Yayoi Kimura

PROVIDER: PXD041546 | JPOST Repository | Wed Apr 10 00:00:00 BST 2024

REPOSITORIES: jPOST

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Use of data-independent acquisition mass spectrometry to identify an objective serum indicator of the need for osteoporotic therapeutic intervention.

Nakai Yusuke Y Kumagai Ken K Ino Yoko Y Akiyama Tomoko T Moriyama Kayano K Takeda Yuriko Y Egashira Kenji K Ohira Takashi T Ryo Akihide A Saito Tomoyuki T Inaba Yutaka Y Hirano Hisashi H Kimura Yayoi Y

Journal of proteomics 20240402

Osteoporosis is characterized by weakened bone microstructure and loss of bone mass. Current diagnostic criteria for osteoporosis are based on the T-score, which is a measure of bone mineral density. However, osteoporotic fragility fractures can occur regardless of the T-score, underscoring the need for additional criteria for the early detection of patients at fracture risk. To identify indicators of reduced bone strength, we performed serum proteomic analysis using data-independent acquisition ...[more]

PMID: 38574990

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Project description:Osteoporosis is the consequence of altered bone metabolism resulting in the systemic reduction of bone strength and increased risk of fragility fractures. MicroRNAs (miRNAs) regulate gene expression on a post-transcriptional level are known to take part in the control of bone formation and bone resorption. Recently, targeted secretion of miRNAs from cells originating from various tissues has been described, which allows for their minimal-invasive detection in serum/plasma and use as biomarkers for presence and progression of pathological conditions. One pilot study has reported circulating miRNAs in serum and tissue of fracture patients. However, further studies are required to explore whether a dysbalance in bone homeostasis of fracture patients can reliably be reflected by specific circulating miRNAs, and whether these miRNAs might serve as drugable targets. Here, we report results from a comprehensive multiplex study of 175 miRNAs in serum samples obtained from 7 patients with osteoporotic fractures at the femoral neck, and 7 age-matched controls. Following elaborate quality control statistical analysis of this exploratory dataset identified 9 microRNAs with altered serum levels in response to fracture (adjusted p-value < 0.1). Of these, hsa-miR-10a/b gave excellent discrimination of both groups (AUC = 1.0), and clustering of samples based on the top10 miRNAs confirmed the high discriminatory power of circulating microRNAs for osteoporotic fractures. In the next step 3 miRNAs with unknown roles in osteogenic differentiation and 4 miRNA from a previous study were tested for their effects on osteogenic differentiation. Of these, 3 miRNAs showed robust effects on osteogenic differentiation. Overall, these data provide important insights into changes in serum miRNA in post-traumatic patients. Future studies will show, whether this knowledge can be used to improve current diagnostic methodologies to predict fracture risk and design novel treatment strategies for osteoporosis patients. Two groups with n=7 per group; one groups represents cases with osteoporotic fractures, the control group is age-matched without fractures

Project description:Background: IL-33, a cytokine with pleiotropic functions, is elevated in serum of patients with hepatocellular carcinoma (HCC). This study investigated effects of local IL-33 expression in resected HCC on patient survival and on immunological and molecular tumor microenvironment. Methods: Tissue of resected HCCs was stained for H&E, masson trichrome, alpha smooth muscle actin, IL-33, CD8 and IL-13 and analysed by flow cytometry. Besides histomorphologic evaluation, the immunohistochemical stainings were analysed for the respective cell numbers separately for tumor area, infiltrative margin and distant liver stroma. These findings were correlated with clinical data and patient outcome. Further, gene expression of different HCC risk groups was compared using Micro Arrays. Results: In multivariable analysis, infiltration of HCCs by IL-33+ cells (P=0.032) and CD8+ cells (P=0.014) both independently were associated with prolonged patient survival. Flow cytometry demonstrated that cytotoxically active CD8+CD62L-KLRG1+CD107a+ effectory-memory cells are the main producers of IL-33 in these HCC patients. Using infiltration by IL-33+ and CD8+ cells as two separate factors, a HCC immune score (HCCIS) was designed and evaluated that stratified patient survival (P=0.0004). This HCCIS identified high and low risk patients who differ in gene expression profiles (P<0.001). Conclusion: Infiltration of HCCs by IL-33+ and CD8+ cells is independently associated with prolonged patient survival. We suggest that this is due to an induction of highly effective cytotoxically active CD8+CD62L-KLRG1+CD107a+ effector-memory cells producing IL-33. Based on these two independent factors we established a HCC immune score that provides risk stratification for HCC patients and can be used in the clinical setting. To investigate if HCCIS 0 high risk and HCCIS 2 low risk tumors exhibit a distinct molecular environment and gene expression pattern, RNA from fresh tumor tissue was isolated and analyzed by whole genome Microarray 4 patients with low risk tumors (HCCIS 2) were compared to 4 patients with high risk tumors (HCCIS 0).

Dataset Information

Use of data-independent acquisition mass spectrometry to identify an objective serum indicator of the need for osteoporotic therapeutic intervention

Publications

Use of data-independent acquisition mass spectrometry to identify an objective serum indicator of the need for osteoporotic therapeutic intervention.

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