Proteomic analysis of Class IV lupus nephritis

Alaiya, Ayodele; Assad, Lina; Alkhafaji, Dania; Shinwari, Zakia; Almana, Hadeel; Shoukri, Mohamed; Alkorbi, Lutfi; Ibrahim, Hossamaldin Galal; Abdelsalam, Mohamed Said; Skolnik, Edward Y.; Adra, Chaker N.; Albaqumi, Mamdouh

doi:10.1093/ndt/gfu215

Cited by 27 publications

(33 citation statements)

References 32 publications

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“…The sample analysis was done on a Triazaic Nano source (Waters, Manchester, UK) and ionization in the positive ion mobility mode nanoESI as previously described. 15,16 The Progenesis QI for Proteomics version 2.0.5387 (Nonlinear Dynamics/ Waters, Manchester, UK) was used for all automated data processing and database searching using the Uniprot database (www.uniprot.org) for protein identification. The data were filtered to show only unambiguous protein identification using multiple parameters including expected molecular mass, percentage coverage, peptides count, unique peptides and confidence scores.…”

Section: Proteomic Analysis: Protein In-solution Digestion and Proteimentioning

confidence: 99%

PD‐L1 promotes OCT4 and Nanog expression in breast cancer stem cells by sustaining PI3K/AKT pathway activation

Almozyan

Çolak

Mansour

et al. 2017

Intl Journal of Cancer

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193

120

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The expression of PD‐L1 in breast cancer is associated with estrogen receptor negativity, chemoresistance and epithelial‐to‐mesenchymal transition (EMT), all of which are common features of a highly tumorigenic subpopulation of cancer cells termed cancer stem cells (CSCs). Hitherto, the expression and intrinsic role of PD‐L1 in the dynamics of breast CSCs has not been investigated. To address this issue, we used transcriptomic datasets, proteomics and several in vitro and in vivo assays. Expression profiling of a large breast cancer dataset (530 patients) showed statistically significant correlation (p < 0.0001, r = 0.36) between PD‐L1 expression and stemness score of breast cancer. Specific knockdown of PD‐L1 using ShRNA revealed its critical role in the expression of the embryonic stem cell transcriptional factors: OCT‐4A, Nanog and the stemness factor, BMI1. Conversely, these factors could be induced upon PD‐L1 ectopic expression in cells that are normally PD‐L1 negative. Global proteomic analysis hinted for the central role of AKT in the biology of PD‐L1 expressing cells. Indeed, PD‐L1 positive effect on OCT‐4A and Nanog was dependent on AKT activation. Most importantly, downregulation of PD‐L1 compromised the self‐renewal capability of breast CSCs in vitro and in vivo as shown by tumorsphere formation assay and extreme limiting dilution assay, respectively. This study demonstrates a novel role for PD‐L1 in sustaining stemness of breast cancer cells and identifies the subpopulation and its associated molecular pathways that would be targeted upon anti‐PD‐L1 therapy.

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Section: Proteomic Analysis: Protein In-solution Digestion and Proteimentioning

confidence: 99%

PD‐L1 promotes OCT4 and Nanog expression in breast cancer stem cells by sustaining PI3K/AKT pathway activation

Almozyan

Çolak

Mansour

et al. 2017

Intl Journal of Cancer

Self Cite

193

120

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“…The present study is the first report, to our knowledge, of LN kidney proteomics using FFPE tissue. While we do find in OPEN ACCESS Freely available online J Proteomics Bioinform, Volume 12(7) 111-112 the literature three reports of global proteomic analysis of renal tissue in LN, these used only fresh-frozen kidney biopsies from a small number of patients with one or two classes of LN [1,2,14]. While we did not find reports on LN kidney proteomics using FFPE tissue, we did find one proteomics study comparing FFT to FFPE kidney tissue.…”

Section: Discussionmentioning

confidence: 83%

“…However, for many chronic progressive diseases such as lupus nephritis (LN), this is unattainable, because FFTs must come from invasive biopsies with minimal tissue availability. Consequently, the proteome of LN has been evaluated in a small number of fresh-frozen kidney biopsies [1,2], which does not cover the full spectrum of LN. Advances in mass spectrometry (MS), especially improved protein digestion and direct quantification techniques, have made proteome analyses feasible for complex tissues.…”

Section: Introductionmentioning

confidence: 99%

Quantitative Proteomics Using Formalin-fixed, Paraffin-embedded Biopsy Tissues in Inflammatory Disease

Amarnani

Capri²,

Souda³

et al. 2019

J Proteomics Bioinform

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Background: Investigations in human disease pathogenesis have been hampered due to paucity of access to fresh-frozen tissues (FFT) for use in global, data-driven methodologies. As an alternative, formalin-fixed, paraffinembedded (FFPE) tissues are readily available in pathology banks. However, the use of formalin for fixation can lead to the loss of proteins that appear during inflammation, thus introducing an inherent sample bias. To address this, we compared FF and FFPE tissue proteomics to determine whether FFPE-tissue can be used effectively in inflammatory diseases.Methods: Adjacent kidney slices from lupus nephritic mice were processed as FFPE or FFTs. Their tissue lysates were run together using proteomics workflow involving filter-aided sample preparation, in-solution dimethyl isotope labeling, StageTip fractionation, and nano-LC MS/MS through an Orbitrap XL MS. Results:We report a >97% concordance in protein identification between adjacent FFPE and FFTs in murine lupus nephritic kidneys. Specifically, proteins representing pathways, namely, 'systemic lupus erythematosus', 'interferon-α', 'TGF-β', and 'extracellular matrix', were reproducibly quantified between FFPE and FFTs. However, 12%-29% proteins were quantified differently in FFPE compared to FFTs, but the differences were consistent across experiments. In particular, certain proteins represented in pathways, including 'inflammatory response' and 'innate immune system' were quantified less in FFPE than in FFTs. In a pilot study of human FFPE tissues, we identified proteins relevant to pathogenesis in lupus nephritic kidney biopsies compared to control kidneys.Conclusion: This is the first report of lupus nephritis kidney proteomics using FFPE tissue. We concluded that archived FFPE tissues can be reliably used for proteomic analyses in inflammatory diseases, with a caveat that certain proteins related to immunity and inflammation may be quantified less in FFPE than in FFTs.

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“…As for LN, 5 biomarkers from kidney biopsy tissue of class IV LN patients were identified: serotransferrin, cytokeratin 18 and 19, albumin, and annexin A5 [71]. Additionally, 5 of the 11 biomarkers that were reproduced in multiple studies were also isolated from kidney tissue as well as from urine, serum, and/or PBMCs, suggesting that these could be used as potential tools for diagnosing LN.…”

Section: Novel Sle Testingmentioning

confidence: 99%

“…Additionally, 5 of the 11 biomarkers that were reproduced in multiple studies were also isolated from kidney tissue as well as from urine, serum, and/or PBMCs, suggesting that these could be used as potential tools for diagnosing LN. For example, alpha-1-antitrypsin (A1AT) which is produced in the kidney in response to injury [72] was found in the urine of during renal flares [71]. …”

Section: Novel Sle Testingmentioning

confidence: 99%

Diagnostic and prognostic tests in systemic lupus erythematosus

Wahezi

Putterman

2017

Best Practice & Research Clinical Rheumatology

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Systemic lupus erythematous (SLE) is a chronic autoimmune inflammatory disease characterized by autoantibodies directed against numerous self-nuclear antigens. Due to the heterogeneous nature of lupus, it has been challenging to identify markers that are sensitive and specific enough for its diagnosis and monitoring. However, with the sequencing of the human genome, rapid development of high throughput approaches has allowed for a better understanding of the etiopathogenesis of complex diseases, including SLE. Here we will present a review of the latest advancements in biomarker discovery during the ‘omics’ era, using these novel technologies, for assisting in the diagnosis and prognosis of patients with SLE.

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Proteomic analysis of Class IV lupus nephritis

Abstract: There is no strong evidence to support a different outcome between the two subcategories of Class-IV LN and, they should thus be treated the same until further studies indicate otherwise.

Cited by 27 publications

References 32 publications

PD‐L1 promotes OCT4 and Nanog expression in breast cancer stem cells by sustaining PI3K/AKT pathway activation

PD‐L1 promotes OCT4 and Nanog expression in breast cancer stem cells by sustaining PI3K/AKT pathway activation

Quantitative Proteomics Using Formalin-fixed, Paraffin-embedded Biopsy Tissues in Inflammatory Disease

Diagnostic and prognostic tests in systemic lupus erythematosus

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