Proteomic alterations in early stage cervical cancer

Güzel, Coşkun; Govorukhina, Natalia; Wisman, G. Bea A.; Stingl, Christoph; Dekker, Lennard J. M.; Klip, Harry G.; Hollema, Harry; Guryev, Victor; Horvatovich, Péter; Zee, Ate G.J. van der; Bischoff, Rainer; Luider, Theo M.

doi:10.18632/oncotarget.24773

Cited by 22 publications

(28 citation statements)

References 44 publications

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“…PRM was essentially performed as described previously 19 and details are reported in Data S2. In short, 20 lL of CSF was digested overnight by trypsin.…”

Section: Prm Validationmentioning

confidence: 99%

Novel CSF biomarkers in genetic frontotemporal dementia identified by proteomics

Ende

Meeter

Stingl³

et al. 2019

Ann Clin Transl Neurol

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Objective To identify novel CSF biomarkers in GRN ‐associated frontotemporal dementia ( FTD ) by proteomics using mass spectrometry ( MS ). Methods Unbiased MS was applied to CSF samples from 19 presymptomatic and 9 symptomatic GRN mutation carriers and 24 noncarriers. Protein abundances were compared between these groups. Proteins were then selected for validation if identified by ≥4 peptides and if fold change was ≤0.5 or ≥2.0. Validation and absolute quantification by parallel reaction monitoring ( PRM ), a high‐resolution targeted MS method, was performed on an international cohort ( n = 210) of presymptomatic and symptomatic GRN , C9orf72 and MAPT mutation carriers. Results Unbiased MS revealed 20 differentially abundant proteins between symptomatic mutation carriers and noncarriers and nine between symptomatic and presymptomatic carriers. Seven of these proteins fulfilled our criteria for validation. PRM analyses revealed that symptomatic GRN mutation carriers had significantly lower levels of neuronal pentraxin receptor ( NPTXR ), receptor‐type tyrosine‐protein phosphatase N2 ( PTPRN 2), neurosecretory protein VGF , chromogranin‐A ( CHGA ), and V‐set and transmembrane domain‐containing protein 2B ( VSTM 2B) than presymptomatic carriers and noncarriers. Symptomatic C9orf72 mutation carriers had lower levels of NPTXR , PTPRN 2, CHGA , and VSTM 2B than noncarriers, while symptomatic MAPT mutation carriers had lower levels of NPTXR and CHGA than noncarriers. Interpretation We identified and validated five novel CSF biomarkers in GRN ‐ associated FTD . Our results show that synaptic, secretory vesicle, and inflammatory proteins are dysregulated in the symptomatic stage and may provide new insights into the pathophysiology of genetic FTD. Further validation is needed to investigate their clinical applicability as diagnostic or monitoring biomarkers.

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“…PRM was essentially performed as described previously 19 and details are reported in Data S2. In short, 20 lL of CSF was digested overnight by trypsin.…”

Section: Prm Validationmentioning

confidence: 99%

Novel CSF biomarkers in genetic frontotemporal dementia identified by proteomics

Ende

Meeter

Stingl³

et al. 2019

Ann Clin Transl Neurol

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“…The analysis of these tissue subsections makes it possible to select specific cell types, or stroma components and to identify with MS more than 3,400 proteins (Clair et al, ). The sample processing after LCM is similar to normal bottom‐up proteomics (Güzel et al, ). Clair et al described a method, whereby tissue is selected with LCM, followed by sonication, and online trypsin digestion followed by MS analysis, which only takes 50 min, in comparison to almost 2 workdays when overnight trypsin digestion is performed.…”

Section: Techniques To Analyze Collagenmentioning

confidence: 99%

Collagen analysis with mass spectrometry

Huizen

IJzermans

Burgers

et al. 2019

Mass Spectrometry Reviews

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Mass spectrometry‐based techniques can be applied to investigate collagen with respect to identification, quantification, supramolecular organization, and various post‐translational modifications. The continuous interest in collagen research has led to a shift from techniques to analyze the physical characteristics of collagen to methods to study collagen abundance and modifications. In this review, we illustrate the potential of mass spectrometry for in‐depth analyses of collagen.

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“…Among these associated genes we find PCM1 (FDR ENET = 0.032), classified to the cell cycle control network, was previously discovered to be associated with the early stage of cervical cancer [69]. SPR (FDR Lasso = 0.003) is located within…”

Section: Yjefn3 Spata5l1 C5orf55 Ppip5k2 Esco2 and Znf225) Are Simentioning

confidence: 94%

Leveraging Methylation Alterations to Discover Potential Causal Genes Associated with the Survival Risk of Cervical Cancer in TCGA through a Two-stage Inference Approach

Zhang

Wang

et al. 2020

Preprint

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Background：Multiple genes were previously identified to be associated with cervical cancer; however, the genetic architecture of cervical cancer remains unknown and many causal genes have yet been discovered.Methods: To explore causal genes related to cervical cancer, a two-stage causal inference approach was proposed within the framework of Mendelian randomization, where the gene expression was treated as exposure, with methylations located within that gene serving as instrumental variables. Five prediction models were first utilized to characterize the relationship between the expression and methylations for each gene; then the methylation-regulated gene expression (MReX) was obtained and the association was evaluated via Cox mixed-effects model based on MReX. We further implemented the harmonic mean p-value (HMP) combination to take advantage of respective strengths of these prediction models while accounting for dependency among the p-values.Results: A total of 14 causal genes were discovered to be associated with the survival risk of cervical cancer in TCGA when the five prediction models were separately employed. The total number of causal genes was brought to 23 when conducting HMP. Some of the newly discovered genes may be novel (e.g. YJEFN3, SPATA5L1, IMMP1L, C5orf55, PPIP5K2, ZNF330, CRYZL1, PPM1A, ESCO2, ZNF605, ZNF225, ZNF266, FICD and OSTC). Functional analyses showed these genes were enriched in tumor-associated pathways. Additionally, four genes (i.e. COL6A1, SYDE1, ESCO2 and GIPC1) were differentially expressed.Conclusion: Overall, our study discovered promising candidate genes that are causally associated with the survival risk of cervical cancer and thus provided new insights into the genetic etiology of cervical cancer.

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Proteomic alterations in early stage cervical cancer

Cited by 22 publications

References 44 publications

Novel CSF biomarkers in genetic frontotemporal dementia identified by proteomics

Novel CSF biomarkers in genetic frontotemporal dementia identified by proteomics

Collagen analysis with mass spectrometry

Leveraging Methylation Alterations to Discover Potential Causal Genes Associated with the Survival Risk of Cervical Cancer in TCGA through a Two-stage Inference Approach

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