Serum protein profiling reveals a specific upregulation of the immunomodulatory protein progranulin in COVID-19

Abstract Background Severe courses of COVID-19 are associated with elevated levels of interleukin 6. However, there is a growing body of evidence pointing to a broad and more complex disorder of pro-inflammatory and anti-viral responses with disturbed interferon signaling in COVID-19. Methods In this prospective single-center registry, we included SARS-CoV-2 positive patients and patients with similar symptoms and severity of disease but negative for SARS-CoV-2 admitted to the emergency department and compared their serum protein expression profiles. Results Interleukin-6 abundance was similar in SARS-CoV-2 positive patients (n = 24) compared to SARS-CoV-2 negative control (n = 61). In contrast, we observed a specific upregulation of the immunomodulatory protein progranulin (GRN). High GRN abundance was associated with adverse outcomes and increased expression of interleukin-6 in COVID-19. Conclusion The data from this registry reveals that GRN is specifically upregulated in SARS-CoV-2 positive patients while interleukin-6 may serve as marker for disease severity. The potential of GRN as a biomarker and a possible impact of increased GRN expression on interferon signaling, virus elimination, and virus-induced lung tissue damage in COVID-19 should be further explored.

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The Jekyll and Hyde of Cellular Senescence in Cancer

Cells ◽

10.3390/cells10020208 ◽

2021 ◽

Vol 10 (2) ◽

pp. 208

Author(s):

Dilara Demirci ◽

Bengisu Dayanc ◽

Fatma Aybuke Mazi ◽

Serif Senturk

Keyword(s):

Cancer Cell ◽

Cellular Senescence ◽

Expression Profiles ◽

Treatment Strategies ◽

Gene Expression Profiles ◽

Therapy Resistance ◽

Disease Recurrence ◽

Adverse Outcomes ◽

Cell Senescence ◽

Great Promise

Cellular senescence is a state of stable cell cycle arrest that can be triggered in response to various insults and is characterized by distinct morphological hallmarks, gene expression profiles, and the senescence-associated secretory phenotype (SASP). Importantly, cellular senescence is a key component of normal physiology with tumor suppressive functions. In the last few decades, novel cancer treatment strategies exploiting pro-senescence therapies have attracted considerable interest. Recent insight, however, suggests that therapy-induced senescence (TIS) elicits cell-autonomous and non-cell-autonomous implications that potentially entail detrimental consequences, reflecting the Jekyll and Hyde nature of cancer cell senescence. In essence, the undesirable manifestations that generally culminate in inflammation, cancer stemness, senescence reversal, therapy resistance, and disease recurrence are dictated by the persistent accumulation of senescent cells and the SASP. Thus, mitigating these pro-tumorigenic effects by eliminating these cells or inhibiting their SASP production holds great promise for developing innovative therapeutic strategies. In this review, we describe the fundamental aspects and dynamics of cancer cell senescence and summarize the comprehensive research on the adverse outcomes of TIS. Furthermore, we underline the rationale and motivation of emerging senotherapeutic modalities surrounding the removal of senescent cells and the SASP to help maximize the overall efficacy of cancer therapies.

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Identification of biomarkers for radiation-induced acute intestinal symptoms (RIAISs) in cervical cancer patients by serum protein profiling

Journal of Radiation Research ◽

10.1093/jrr/rru081 ◽

2014 ◽

Vol 56 (1) ◽

pp. 134-140 ◽

Cited By ~ 7

Author(s):

Y. Chai ◽

J. Wang ◽

Y. Gao ◽

T. Wang ◽

F. Shi ◽

...

Keyword(s):

Cervical Cancer ◽

Cancer Patients ◽

Serum Protein ◽

Protein Profiling ◽

Radiation Induced ◽

Intestinal Symptoms

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S1124 Serum Protein Profiling Predicting Outcome in Acute Severe Ulcerative Colitis

Gastroenterology ◽

10.1016/s0016-5085(09)60873-8 ◽

2009 ◽

Vol 136 (5) ◽

pp. A-194

Author(s):

Nicola C. Hare ◽

Margaret Imrie ◽

Kimberley Soo ◽

Amanda Smith ◽

Robert Gray ◽

...

Keyword(s):

Ulcerative Colitis ◽

Serum Protein ◽

Protein Profiling ◽

Severe Ulcerative Colitis ◽

Predicting Outcome

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PATH-29. GLIOBLASTOMA TUMOR CLASSIFICATION BASED ON SPATIAL ANALYSIS OF ONCOGENIC AMPLIFICATIONS AND PROTEIN EXPRESSION

Neuro-Oncology ◽

10.1093/neuonc/noab196.481 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi121-vi121

Author(s):

Kacper Walentynowicz ◽

Dalit Engelhardt ◽

Shreya Yadav ◽

Ugoma Onubogu ◽

Roberto Salatino ◽

...

Keyword(s):

Tumor Microenvironment ◽

Protein Expression ◽

Single Cell ◽

Expression Profiles ◽

Protein Profiling ◽

Intratumor Heterogeneity ◽

Neuronal Markers ◽

Associated Proteins ◽

Dual Amplification ◽

Protein Expression Profiles

Abstract Heterogeneity of glioblastoma (GBM) has been extensively studied in recent years with identification of oncogenic drivers of GBM cellular subtypes. However, little is known about how these cells interact with each other or with the surrounding tumor microenvironment (TME). We employed spatial protein profiling targeting immune and neuronal markers (79 proteins) coupled with single-cell spatial maps of fluorescence in situ hybridization (FISH) for EGFR, CDK4, and PDGFRA on human GBM tissue sections. Several cores from 20 GBM samples were collected to create a tissue microarray, and 96 regions of interests were profiled with 37,844 nuclei for oncogenic amplification screen. Spatial protein profiling identified strong correlation of certain immune markers, TAU-associated proteins, and oligodendrocyte-enriched protein groups and overall high intratumor heterogeneity of TME. Our single-cell quantification of FISH signals showed differences among tumors based on the prevalence of dual amplification of EGFR and CDK4 within a cell relative to single oncogene amplified cells. High relative frequency of dual amplification was associated with increased expression of immune-related markers and decreased expression of EGFR protein. Moreover, this protein expression signature was associated with survival in another GBM dataset. Here, we present spatial genetic analysis at the single cell level coupled with protein expression profiles associated with tumor microenvironment. Our results suggest that assessment of genetic heterogeneity in GBM could potentially drive improved patient stratification and treatment.

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Serum protein profiling in mice: Identification of Factor XIIIa as a potential biomarker for muscular dystrophy

PROTEOMICS ◽

10.1002/pmic.200700857 ◽

2008 ◽

Vol 8 (8) ◽

pp. 1552-1563 ◽

Cited By ~ 41

Author(s):

Sharmini Alagaratnam ◽

Bart J. A. Mertens ◽

Johannes C. Dalebout ◽

André M. Deelder ◽

Gert-Jan B. van Ommen ◽

...

Keyword(s):

Muscular Dystrophy ◽

Serum Protein ◽

Protein Profiling ◽

Factor Xiiia ◽

Potential Biomarker

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Identification of a new marker of hepatocellular carcinoma by serum protein profiling of patients with chronic liver diseases

Hepatology ◽

10.1002/hep.20505 ◽

2004 ◽

Vol 41 (1) ◽

pp. 40-47 ◽

Cited By ~ 166

Author(s):

Valérie Paradis ◽

Francoise Degos ◽

Delphine Dargère ◽

Nanou Pham ◽

Jacques Belghiti ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Serum Protein ◽

Liver Diseases ◽

Chronic Liver ◽

Protein Profiling ◽

Chronic Liver Diseases

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Identification of patients with nasopharyngeal carcinoma by serum protein profiling using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry

International Journal of Clinical Oncology ◽

10.1007/s10147-013-0621-y ◽

2013 ◽

Vol 19 (4) ◽

pp. 579-585 ◽

Cited By ~ 2

Author(s):

Xiao-dong Zhu ◽

Fang Su ◽

Zhong-guo Liang ◽

Ling Li ◽

Song Qu ◽

...

Keyword(s):

Mass Spectrometry ◽

Nasopharyngeal Carcinoma ◽

Serum Protein ◽

Laser Desorption ◽

Protein Profiling ◽

Laser Desorption Ionization ◽

Ionization Time ◽

Desorption Ionization ◽

Flight Mass Spectrometry ◽

Surface Enhanced

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INTERLEUKIN-6 AND THE RISK OF ADVERSE OUTCOMES IN PATIENTS AFTER AN ACUTE CORONARY SYNDROME: OBSERVATIONS FROM THE SOLID-TIMI 52 TRIAL

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(16)30443-0 ◽

2016 ◽

Vol 67 (13) ◽

pp. 442

Author(s):

Christina Fanola ◽

David Morrow ◽

Christopher Cannon ◽

Petr Jarolim ◽

Mary Ann Lukas ◽

...

Keyword(s):

Acute Coronary Syndrome ◽

Interleukin 6 ◽

Adverse Outcomes ◽

Coronary Syndrome

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LncRNA Profiling Reveals That the Deregulation of H19, WT1-AS, TCL6, and LEF1-AS1 Is Associated with Higher-Risk Myelodysplastic Syndrome

Cancers ◽

10.3390/cancers12102726 ◽

2020 ◽

Vol 12 (10) ◽

pp. 2726

Author(s):

Katarina Szikszai ◽

Zdenek Krejcik ◽

Jiri Klema ◽

Nikoleta Loudova ◽

Andrea Hrustincova ◽

...

Keyword(s):

Myelodysplastic Syndrome ◽

Bone Marrow Cells ◽

Expression Profiles ◽

Chromatin Modification ◽

Adverse Outcomes ◽

Disease Pathogenesis ◽

Protein Coding ◽

Hematopoietic Stem ◽

Risk Of Progression ◽

Patient Prognosis

Background: myelodysplastic syndrome (MDS) is a hematopoietic stem cell disorder with an incompletely known pathogenesis. Long noncoding RNAs (lncRNAs) play multiple roles in hematopoiesis and represent a new class of biomarkers and therapeutic targets, but information on their roles in MDS is limited. Aims: here, we aimed to characterize lncRNAs deregulated in MDS that may function in disease pathogenesis. In particular, we focused on the identification of lncRNAs that could serve as novel potential biomarkers of adverse outcomes in MDS. Methods: we performed microarray expression profiling of lncRNAs and protein-coding genes (PCGs) in the CD34+ bone marrow cells of MDS patients. Expression profiles were analyzed in relation to different aspects of the disease (i.e., diagnosis, disease subtypes, cytogenetic and mutational aberrations, and risk of progression). LncRNA-PCG networks were constructed to link deregulated lncRNAs with regulatory mechanisms associated with MDS. Results: we found several lncRNAs strongly associated with disease pathogenesis (e.g., H19, WT1-AS, TCL6, LEF1-AS1, EPB41L4A-AS1, PVT1, GAS5, and ZFAS1). Of these, downregulation of LEF1-AS1 and TCL6 and upregulation of H19 and WT1-AS were associated with adverse outcomes in MDS patients. Multivariate analysis revealed that the predominant variables predictive of survival are blast count, H19 level, and TP53 mutation. Coexpression network data suggested that prognosis-related lncRNAs are predominantly related to cell adhesion and differentiation processes (H19 and WT1-AS) and mechanisms such as chromatin modification, cytokine response, and cell proliferation and death (LEF1-AS1 and TCL6). In addition, we observed that transcriptional regulation in the H19/IGF2 region is disrupted in higher-risk MDS, and discordant expression in this locus is associated with worse outcomes. Conclusions: we identified specific lncRNAs contributing to MDS pathogenesis and proposed cellular processes associated with these transcripts. Of the lncRNAs associated with patient prognosis, the level of H19 transcript might serve as a robust marker comparable to the clinical variables currently used for patient stratification.

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