Digital Polymerase Chain Reaction Quantification of SERPINA1 Predicts Prognosis in High-Grade Glioma

Ookawa, Satoshi; Wanibuchi, Masahiko; Kataoka‐Sasaki, Yuko; Sasaki, Masanori; Oka, Shinichi; Ohtaki, Shunya; Noshiro, Shouhei; Komatsu, Katsuya; Akiyama, Yukinori; Mikami, Takeshi; Mikuni, Nobuhiro; Kocsis, Jeffery D.

doi:10.1016/j.wneu.2017.12.166

Cited by 14 publications

(11 citation statements)

References 25 publications

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“…Among the three differentially expressed proteins, Serpina1 and AGP were identified as potential plasma biomarkers for their stable expression trends in the early stage of DAI. Serpina1, an inhibitor of serine protease and neurotrypsin, was significantly decreased in plasma subjects of injury group compared with controls [24]. Serpina1 plays an essential anti-inflammatory role in protecting tissues from proteolytic mechanisms [24].…”

Section: Discussionmentioning

confidence: 99%

“…Serpina1, an inhibitor of serine protease and neurotrypsin, was significantly decreased in plasma subjects of injury group compared with controls [24]. Serpina1 plays an essential anti-inflammatory role in protecting tissues from proteolytic mechanisms [24]. Recent studies indicate that Serpina1 is associated with various diseases, such as sporadic amyotrophic lateral sclerosis, cancers, schizophrenia, bipolar disorder, and frontotemporal dementia [24,25,26,27].…”

Section: Discussionmentioning

confidence: 99%

“…Serpina1 plays an essential anti-inflammatory role in protecting tissues from proteolytic mechanisms [24]. Recent studies indicate that Serpina1 is associated with various diseases, such as sporadic amyotrophic lateral sclerosis, cancers, schizophrenia, bipolar disorder, and frontotemporal dementia [24,25,26,27]. Furthermore, a recent study by Peng et al indicated that up-regulation of Serpina1 could suppress agrin-22 production and eventually lead to synaptic dysfunction [28].…”

Section: Discussionmentioning

confidence: 99%

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Integrated Proteomics and Metabolomic Analyses of Plasma Injury Biomarkers in a Serious Brain Trauma Model in Rats

Song

Zhu

Zhang

et al. 2019

IJMS

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Diffuse axonal injury (DAI) is a prevalent and serious brain injury with significant morbidity and disability. However, the underlying pathogenesis of DAI remains largely unclear, and there are still no objective laboratory-based tests available for clinicians to make an early diagnosis of DAI. An integrated analysis of metabolomic data and proteomic data may be useful to identify all of the molecular mechanisms of DAI and novel potential biomarkers. Therefore, we established a rat model of DAI, and applied an integrated UPLC-Q-TOF/MS-based metabolomics and isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomic analysis to obtain unbiased profiling data. Differential analysis identified 34 metabolites and 43 proteins in rat plasma of the injury group. Two metabolites (acetone and 4-Hydroxybenzaldehyde) and two proteins (Alpha-1-antiproteinase and Alpha-1-acid glycoprotein) were identified as potential biomarkers for DAI, and all may play important roles in the pathogenesis of DAI. Our study demonstrated the feasibility of integrated metabolomics and proteomics method to uncover the underlying molecular mechanisms of DAI, and may help provide clinicians with some novel diagnostic biomarkers and therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Integrated Proteomics and Metabolomic Analyses of Plasma Injury Biomarkers in a Serious Brain Trauma Model in Rats

Song

Zhu

Zhang

et al. 2019

IJMS

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“…The results were screened by the criteria: |logFC| > 2, FDR<0.05. Among these DEGs, we selected 6 hub genes (FPR2, VEGFA, SERPINA1, SOX2, PBK, ITGB3) with a higher degree of connectivity and could be a potential biomarker for GBM prognosis [20,27,47,49]. The considerably different expression level of FPR2 was presented in violin plots and box plots.…”

Section: Discussionmentioning

confidence: 99%

Genomic profiling of cancerous patients identifies FPR2 as an alternative immunotherapeutic target in glioblastoma multiforme

Sun¹,

Qiu²,

Yang³

et al. 2020

Preprint

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BackgroundGlioblastoma multiforme (GBM) is a type of high-grade brain tumor known for its proliferative, invasive property, and low survival rate. Recently, with the advancement in therapeutics for tumors such as targeted therapy, individual cancer-specific biomarkers could be recognized as targets for curative purposes. This study identified six differentially expressed genes that have shown significant implications in clinical field, including FPR2, VEGFA, SERPINA1, SOX2, PBK, and ITGB3. FPR2 was of the same protein family with FPR1, and the latter has been repeatedly reported to promote motility and invasiveness of multiple tumor forms.MethodsThe gene expression profiling of 40 GBM samples and five normal samples from the TCGA database were comprehensively analyzed. The differentially expressed genes (DEGs) were identified using R package and screened by enrichment analysis and examination of protein–protein interaction networks, in order to further explore the functions of DEGs with the highest association with clinical traits and to find hub genes. A qRT-PCR and Western blots were conducted to verify the results of this study.ResultsOur investigation showed that FPR2, VEGFA, SERPINA1, SOX2, PBK, and ITGB3 were significantly up-regulated in GBM primary tumor compared to the control group. Functional enrichment analysis of the DEGs demonstrated that biological functions related to immune systems, cell division and cell cycle were significantly increased, which were closely related to tumor progression and development. Downstream construction of PPI network analysis indicated that FPR2 was a hub gene involved in high level of interaction with CR3 and VEGFA, which played a key role in inflammatory pathways and cellular dysfunction.ConclusionFPR2, VEGFA, SERPINA1, SOX2, PBK, and ITGB3 were significantly over-expressed in primary tumor samples of GBM patients and were involved in cellular functions and pathways contributing to tumor progression. Out of these six pivotal genes, we intensively focused on FPR2, and our analysis and experimental data both suggested its efficacy as a potential biomarker, serving as an alternative immunotherapeutic target for glioblastoma multiforme.

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“…The term digital polymerase chain reaction was first termed by Kinzlerand and Vogelsteinin in mid-1999 to describe a disruptive methodology for the detection of ras oncogene mutations in the stools of patients with colorectal cancer [30]. Using nanoliter-sized sample droplets, ddPCR provides molecular amplification and quantification of low levels of ctDNA and allelic variants in complex body fluids that are usually not detected by conventional real-time PCR [31,32]. Moreover, the analysis of ctDNA by ddPCR, during post-treatment surveillance of head and neck cancer patients, demonstrated that ddPCR can overcome the insufficient accuracy of imaging technologies for early detection of relapsing diseases [32] (Table 2).…”

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confidence: 99%

Perspective: Cellular and Molecular Profiling Technologies in Personalized Oncology

Cruz

Peng

2019

JPM

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Cancer is a leading cause of death worldwide and therefore one of the most important public health concerns. In this contribution, we discuss recent key enabling technological innovations (and their challenges), including biomarker-based technologies, that potentially allow for decentralization (e.g., self-monitoring) with the increasing availability of point-of-care technologies in the near future. These technological innovations are moving the field one step closer toward personalized oncology.

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Digital Polymerase Chain Reaction Quantification of SERPINA1 Predicts Prognosis in High-Grade Glioma

Cited by 14 publications

References 25 publications

Integrated Proteomics and Metabolomic Analyses of Plasma Injury Biomarkers in a Serious Brain Trauma Model in Rats

Integrated Proteomics and Metabolomic Analyses of Plasma Injury Biomarkers in a Serious Brain Trauma Model in Rats

Genomic profiling of cancerous patients identifies FPR2 as an alternative immunotherapeutic target in glioblastoma multiforme

Perspective: Cellular and Molecular Profiling Technologies in Personalized Oncology

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