Proteomics-Based Approach Reveals the Involvement of SERPINB9 in Recurrent and Relapsed Multiple Myeloma

Chen, Yao; Quan, Lina; Jia, Chuiming; Guo, Yiwei; Wang, Xinya; Zhang, Yu; Jin, Yan; Liu, Aichun

doi:10.1021/acs.jproteome.1c00007

Cited by 10 publications

(9 citation statements)

References 59 publications

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“…Therefore, we should actively explore the specific mechanism of NETs on HUVECs. Due to the relatively low consistency between mRNA and protein expression in some tumor types, proteome analysis may outperform transcriptome analysis in detecting disease-related changes in cell activity and function ( 38 ). Therefore, in our study, proteomic technique was used to understand the changes in protein post-transcriptional translation levels after NETs stimulation of HUVECs.…”

Section: Discussionmentioning

confidence: 99%

Immunoregulation and clinical significance of neutrophils/NETs-ANGPT2 in tumor microenvironment of gastric cancer

Yang

Zou

et al. 2022

Front. Immunol.

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Although significant progress has been made in the study of gastric cancer (GC), clinicians lack reliable protein markers for accurate diagnosis and tumor stratification. Neutrophil extracellular traps (NETs) are networks of extracellular fibers composed of DNA from neutrophils. We have previously reported that abundant NETs are deposited in GC, damaging human umbilical vein endothelial cells (HUVECs) and triggering the release of tissue factors, leading to a hypercoagulable state in GC. However, the specific effects of NETs on HUVECs are unclear. We aimed to explore the functional changes caused by NETs on HUVECs, providing evidence that NETs may fuel GC progression. Through quantitative proteomics, we identified 6182 differentially expressed proteins in NET-stimulated HUVECs by TMT. The reliability of the TMT technique was confirmed by parallel reaction monitoring (PRM) analysis of 17 differentially expressed proteins. Through bioinformatics analysis, we found that NETs upregulate ANGPT2 in HUVECs. We comprehensively analyzed the prognosis, biological function, immune response, and therapeutic value of ANGPT2 in GC. We found that overexpression of ANGPT2 in GC is associated with poor prognosis and potentially regulates multiple biological functions. At the same time, ANGPT2 also predicted immunotherapeutic and chemotherapeutic responses in GC. In conclusion, NETs promoted ANGPT2 overexpression in the GC microenvironment. In the future, the neutrophil/NETs-ANGPT2 axis may provide a new target for the treatment of GC.

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Section: Discussionmentioning

confidence: 99%

Immunoregulation and clinical significance of neutrophils/NETs-ANGPT2 in tumor microenvironment of gastric cancer

Yang

Zou

et al. 2022

Front. Immunol.

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“…In the surface-enhanced laser desorption/ionization timeof-flight mass spectrometry, which is considered as an extended technique of the MALDI-TOF-MS method, the ionized proteins can be directly identified in an electric field by mass spectrometry, without involving protein separation on a 2D gel [ 38 , 39 ]. Over the last decade, electrospray ionization tandem mass spectrometry analysis has become one of the most advanced analytical proteomics methods [ 40 ] and has also been applied in cytologic specimens [ 41 ].…”

Section: The History Of Proteomic Application In Cytologymentioning

confidence: 99%

The application of high-throughput proteomics in cytopathology

Nikas

Ryu²

2022

JPTM

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High-throughput genomics and transcriptomics are often applied in routine pathology practice to facilitate cancer diagnosis, assess prognosis, and predict response to therapy. However, the proteins rather than nucleic acids are the functional molecules defining the cellular phenotype in health and disease, whereas genomic profiling cannot evaluate processes such as the RNA splicing or posttranslational modifications and gene expression does not necessarily correlate with protein expression. Proteomic applications have recently advanced, overcoming the issue of low depth, inconsistency, and suboptimal accuracy, also enabling the use of minimal patient-derived specimens. This review aims to present the recent evidence regarding the use of high-throughput proteomics in both exfoliative and fine-needle aspiration cytology. Most studies used mass spectrometry, as this is associated with high depth, sensitivity, and specificity, and aimed to complement the traditional cytomorphologic diagnosis, in addition to identify novel cancer biomarkers. Examples of diagnostic dilemmas subjected to proteomic analysis included the evaluation of indeterminate thyroid nodules or prediction of lymph node metastasis from thyroid cancer, also the differentiation between benign and malignant serous effusions, pancreatic cancer from autoimmune pancreatitis, non-neoplastic from malignant biliary strictures, and benign from malignant salivary gland tumors. A few cancer biomarkers-related to diverse cancers involving the breast, thyroid, bladder, lung, serous cavities, salivary glands, and bone marrow-were also discovered. Notably, residual liquid-based cytology samples were suitable for satisfactory and reproducible proteomic analysis. Proteomics could become another routine pathology platform in the near future, potentially by using validated multi-omics protocols.

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“…During the past few years, global expression analysis of proteins or proteomics has been widely used in many cancer research studies, including MM [12][13][14][15][16][17][18][19]. Proteomics provides the molecular machinery of cell physiology, including the level of protein expression, protein variations or isoforms, posttranslational modification and protein-protein interactions, providing superior advantages over genomic-based assays [19].…”

Section: Introductionmentioning

confidence: 99%

“…In MM, proteomic analysis has been used for several specific purposes, including studying advanced pathogenesis, identifying novel drug-targeting molecules, and identifying potential diagnostic and prognostic biomarkers [9][10][11]. Several studies have demonstrated the use of the proteomic approach to identify potential biomarkers in MM [14][15][16][17][18]. BM-derived proteomes, such as BM plasma cells and BM extracellular matrix proteomes, were commonly used as the particular protein source for biomarker discovery [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

“…Several studies have demonstrated the use of the proteomic approach to identify potential biomarkers in MM [14][15][16][17][18]. BM-derived proteomes, such as BM plasma cells and BM extracellular matrix proteomes, were commonly used as the particular protein source for biomarker discovery [14][15][16]. However, obtaining protein samples directly from the BM involves a highly invasive and painful procedure and is inappropriate for use as a routine biomarker in clinical practice.…”

Section: Introductionmentioning

confidence: 99%

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Serum proteomic profiling reveals MTA2 and AGO2 as potential prognostic biomarkers associated with disease activity and adverse outcomes in multiple myeloma

et al. 2022

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Multiple myeloma (MM) is an incurable plasma cell malignancy accounting for approximately 10% of hematological malignancies. Identification of reliable biomarkers for better diagnosis and prognosis remains a major challenge. This study aimed to identify potential serum prognostic biomarkers corresponding to MM disease activity and evaluate their impact on patient outcomes. Serum proteomic profiles of patients with MM and age-matched controls were performed using LC–MS/MS. In the verification and validation phases, the concentration of the candidate biomarkers was measured using an ELISA technique. In addition, the association of the proposed biomarkers with clinical outcomes was assessed. We identified 23 upregulated and 15 downregulated proteins differentially expressed in newly diagnosed and relapsed/refractory MM patients compared with MM patients who achieved at least a very good partial response to treatment (≥VGPR). The top two candidate proteins, metastasis-associated protein-2 (MTA2) and argonaute-2 (AGO2), were selected for further verification and validation studies. Both MTA2 and AGO2 showed significantly higher levels in the disease-active states than in the remission states (p < 0.001). Regardless of the patient treatment profile, high MTA2 levels were associated with shorter progression-free survival (p = 0.044; HR = 2.48; 95% CI, 1.02 to 6.02). Conversely, high AGO2 levels were associated with IgG and kappa light-chains isotypes and an occurrence of bone involvement features (p < 0.05) and were associated with prolonged time to response (p = 0.045; HR = 3.00; 95% CI, 1.03 to 8.76). Moreover, the analytic results using a publicly available NCBI GEO dataset revealed that AGO2 overexpression was associated with shorter overall survival among patients with MM (p = 0.032, HR = 1.60, 95% CI, 1.04 to 2.46). In conclusion, MTA2 and AGO2 proteins were first identified as potential biomarkers that reflect disease activity, provide prognostic values and could serve as non-invasive indicators for disease monitoring and outcome predicting among patients with MM.

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Proteomics-Based Approach Reveals the Involvement of SERPINB9 in Recurrent and Relapsed Multiple Myeloma

Cited by 10 publications

References 59 publications

Immunoregulation and clinical significance of neutrophils/NETs-ANGPT2 in tumor microenvironment of gastric cancer

Immunoregulation and clinical significance of neutrophils/NETs-ANGPT2 in tumor microenvironment of gastric cancer

The application of high-throughput proteomics in cytopathology

Serum proteomic profiling reveals MTA2 and AGO2 as potential prognostic biomarkers associated with disease activity and adverse outcomes in multiple myeloma

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