Epigenetic regulation of OAS2 shows disease-specific DNA methylation profiles at individual CpG sites

Gu, Xiaolian; Boldrup, Linda; Coates, Philip J.; Fåhræus, Robin; Nylander, Elisabet; Loizou, Christos P.; Olofsson, Katarina; Norberg‐Spaak, Lena; Gärskog, Ola; Nylander, Karin

doi:10.1038/srep32579

Cited by 25 publications

(15 citation statements)

References 37 publications

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“…As we know, AVPs in the skin, especially in the epidermis, play important roles in barrier defense (35,36). Increased OAS2 expression in psoriasis has been reported in epigenome and transcriptome datasets (37,38). Our proteomics data also showed OAS2 as a significant DEP in both psoriatic epidermis and serum of psoriatic individuals.…”

Section: Discussionsupporting

confidence: 67%

Quantitative Proteomic Profile of Psoriatic Epidermis Identifies OAS2 as a Novel Biomarker for Disease Activity

et al. 2020

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Psoriasis is a common chronic inflammatory systemic disease. Epidermal proteins are considered to be important in maintaining skin barrier function, innate immunity, and inflammation. To define more possible roles of the epidermis in the pathogenesis of psoriasis, quantified proteomic analysis was used to screen and analyze the differentially expressed epidermal proteins between 16 psoriasis patients and 15 healthy controls. Upregulated differential expression proteins (DEPs) include several significant functional protein clusters, including antimicrobial peptides (AMPs) and antiviral proteins (AVPs). The levels of 2-5-oligoadenylate synthase 2 (OAS2) in both epidermis and serum levels were significantly elevated in psoriasis and were also positively correlated with Psoriasis Area Severity Index (PASI) scores and Body Surface Area (BSA) scores. Moreover, OAS2 expression in psoriatic skin significantly decreased after IL-17R mono-antibody treatment. It has been clarified that inflamed keratinocytes were the main source of abnormally increased OAS2 in psoriasis skin by immunofluorescence and primary cell cultures. Keratinocyte-derived OAS2 can be induced by not only IFNβ, but also psoriasis associated cytokines like IL-17A and IL-6. This study revealed that AMPs and AVPs are two important functional protein clusters altering innate immune in psoriatic epidermis. OAS2 is a novel potential sensitive biomarker, which could predict the severity and activity of psoriasis, and could also be used as an indicator to evaluate or monitor the efficacy of clinical treatment.

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Section: Discussionsupporting

confidence: 67%

Quantitative Proteomic Profile of Psoriatic Epidermis Identifies OAS2 as a Novel Biomarker for Disease Activity

et al. 2020

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“…The second gene, OAS2 , is a member of the 2–5A synthetase family which is involved in the immune response to viral infections. Expression of OAS2 has been suggested as a biomarker for disease and it has been reportedly upregulated in psoriasis and squamous cell carcinoma patients (54) and in mice in response to cigarette smoke and influenza virus (55). …”

Section: Discussionmentioning

confidence: 99%

Radiotherapy-Associated Long-term Modification of Expression of the Inflammatory Biomarker Genes ARG1, BCL2L1, and MYC

et al. 2017

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Ionizing radiation (IR) exposure of cells in vitro and in vivo triggers a complex cellular response among which modifications of gene expression have been consistently reported. Nevertheless, little is currently known about the transcriptionally responsive genes which play a role in the inflammation response. In order to improve our understanding of such transcriptional response to radiation in vivo, we simultaneously monitored the expression of 249 genes associated with the inflammation response over the course of the radiotherapy treatment in blood of patients treated for endometrial or head and neck cancer. We have identified genes whose transcriptional expression is either upregulated (ARG1, BCL2L1) or downregulated (MYC) several fold in vivo. These modifications were consistently detected across patients and further confirmed by quantitative real-time polymerase chain reaction (QRT-PCR); they were specifically significant toward the end of the radiotherapy treatment, 5 weeks following the first radiation fraction and more pronounced in endometrial patients (respectively, 2.9, 4.1, and 1.8 times). Importantly, in an attempt to correlate expression levels with normal tissue reaction to IR, we also identified three other genes CD40, OAS2, and CXCR1 whose expression level fluctuations during radiotherapy were more pronounced in patients developing late normal tissue responses to curative radiotherapy after the end of the radiotherapy treatment. Overall, we identified inflammation-associated genes which are promising biomarkers of IR exposure and susceptibility to radiation-induced toxicity.

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“…Patient characteristics are shown in Table . Tissue biopsies had been consecutively collected and some patients were included in our previous studies with different objectives . Biopsies taken from the lateral border of the tongue from 14 healthy volunteers not exposed to classic oral cancer risk factors (smoking and alcohol) had also been collected previously .…”

Section: Methodsmentioning

confidence: 99%

High immune cytolytic activity in tumor‐free tongue tissue confers better prognosis in patients with squamous cell carcinoma of the oral tongue

Boldrup

Coates

et al. 2019

The Journal of Pathology CR

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Immune cells and cytolytic activity within the tumor microenvironment are being intensively studied. Through transcriptome profiling, immune cell enumeration using the xCell tool and cytolytic activity quantification according to granzyme A (GZMA) and perforin (PRF1) mRNA levels, we investigated immunoreactivity in tumor and/or tumor‐free tongue tissue samples from 31 patients with squamous cell carcinoma of the oral tongue and 14 healthy individuals (control tongue tissues). We found significantly altered immune cell compositions (p < 0.001) and elevated cytolytic activity (p < 0.001) in tumor compared to tumor‐free samples, and altered infiltration of a subset of immune cells (e.g. CD8+ T cells, p < 0.01) as well as increased cytolytic activity (p < 0.001) in tumor‐free compared to control samples. Controlling for patient age at diagnosis and tumor stage, Cox regression analysis showed that high cytolytic activity in tumor‐free samples associated with improved disease‐free survival (hazard ratio= 4.20, 95% CI = 1.09–16.20, p = 0.037). However, the degree of cytolytic activity in tumor samples did not provide prognostic information. Taken together, our results show the presence of cancer‐related immune responses in clinically tumor‐free tongue in patients with squamous cell carcinoma of the oral tongue. Measuring cytolytic activity in tumor‐free tongue samples contralateral to tumor might thus be an effective approach to predict clinical outcome.

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Epigenetic regulation of OAS2 shows disease-specific DNA methylation profiles at individual CpG sites

Cited by 25 publications

References 37 publications

Quantitative Proteomic Profile of Psoriatic Epidermis Identifies OAS2 as a Novel Biomarker for Disease Activity

Quantitative Proteomic Profile of Psoriatic Epidermis Identifies OAS2 as a Novel Biomarker for Disease Activity

Radiotherapy-Associated Long-term Modification of Expression of the Inflammatory Biomarker Genes ARG1, BCL2L1, and MYC

High immune cytolytic activity in tumor‐free tongue tissue confers better prognosis in patients with squamous cell carcinoma of the oral tongue

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