A simple and highly efficient method of IFI44L methylation detection for the diagnosis of systemic lupus erythematosus

Zhang, Bo; Liu, Limin; Zhou, Tian; Shi, Xiaoli; Wu, Haijing; Xiang, Zhongyuan; Zhao, Ming; Lu, Qianjin

doi:10.1016/j.clim.2020.108612

Cited by 16 publications

(14 citation statements)

References 22 publications

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“…In this study, we comprehensively analyzed the immune implication of IFI44L in TCGA-NSCLC samples and successfully constructed the IFI44L-related immunomodulator signatures to clarify its Previous studies had suggested that IFI44L participates in tumor progression in certain cancers, including osteosarcoma and hepatocellular carcinoma (16,17). As we all know, IFI44L played a crucial role in anti-virus processes and is competent to be a biomarker in diagnosis of viral infection (13,28,29). However, up to now, the functions and immune implications of IFI44L in NSCLC patients had not been elucidated.…”

Section: Discussionmentioning

confidence: 99%

“…As reported, IFI44L may participate in numerous innate immune processes and could be induced by multiple viruses, including influenza virus and HIV-1 ( 10 – 12 ). In addition, the promoter methylation of IFI44L is a novel and appropriate diagnostic marker for systemic lupus erythematosus (SLE) patients, with a sensitivity of 88.571% and a specificity of 97.087% ( 13 ). Besides, IFI44L has been found to be upregulated after a wide range of viral infection and is involved in antiviral and anti-proliferative respiratory syncytial virus (RSV) infection procedure, suggesting that the IFI44L may serve as a promising biomarker of viral infection ( 14 ).…”

Section: Introductionmentioning

confidence: 99%

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Comprehensive Analysis of Immune Implication and Prognostic Value of IFI44L in Non-Small Cell Lung Cancer

et al. 2022

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Interferon-induced protein 44-like (IFI44L), a type I interferon-stimulated gene (ISG), has been reported to be involved in innate immune processes and to act as a tumor suppressor in several cancers. However, its immune implication on lung cancer remains unclear. Here, we systemically analyzed the immune association of IFI44L with multiple tumor-infiltrating immune cells (TIICs) and immunomodulators through bioinformatics methods in The Cancer Genome Atlas (TCGA) lung cancer cohorts. Then, the IFI44L-related immunomodulators were selected to construct the prognostic signatures in the lung adenocarcinoma (LUAD) cohort and the lung squamous cell carcinoma (LUSC) cohort, respectively. Concordance index and time-dependent receiver operating characteristics (ROC) curves were applied to evaluate the prognostic signatures. GSE72094 and GSE50081 were used to validate the TCGA-LUAD signature and TCGA-LUSC signature, respectively. A nomogram was established by risk score and clinical features in the LUAD cohort. Finally, the prognostic value and biological function of IFI44L were verified in a real-world cohort and in vitro experiments. The results indicated that IFI44L showed significant correlation with TIICs in LUAD and LUSC samples. Functional enrichment analysis showed that IFI44L may participate in various cancer/immune-related pathways, including JAK/STAT signaling pathway and NF-κB signaling pathway. A total of 44 immunomodulators presented obvious association with IFI44L in the TCGA-LUAD cohort and a robust 10-immunomodulator signature was constructed. Patients in the higher-risk group presented worse prognosis than those in the lower-risk group. Notably, the risk signature was successfully validated in GSE72094. Multivariate Cox regression suggested that the risk signature could act as independent prognostic factors in both TCGA-LUAD and GSE72094 cohorts. Besides, a 17-immunomodulator signature was established in the TCGA-LUSC cohort and similar results were presented through analysis. The nomogram exhibited good accuracy in predicting overall survival (OS) outcome among TCGA-LUAD patients than the risk signature and other clinical features, with the area under curve values being 0.782 at 1 year, 0.825 at 3 years, and 0.792 at 5 years. Finally, tissue microarray analysis indicated that higher expression of IFI44L presented opposite relationship with pathological stage (p = 0.016) and a better outcome among lung cancer patients (p = 0.024). Functional experiments found that IFI44L overexpression significantly inhibited the proliferation, migration, and invasion in LUAD and LUSC cells; RT-qPCR experiments verified the correlation between the expression level of IFI44L with multiple immunomodulators in SPC-A-1 and NCI-H520 cells. In conclusion, our research highlighted that IFI44L is associated with tumor immune infiltration and provided information on IFI44L’s immune implication, which indicates that IFI44L has potential clinical immunotherapeutic value and the proposed nomogram is a promising biomarker for non-small cell lung cancer patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Comprehensive Analysis of Immune Implication and Prognostic Value of IFI44L in Non-Small Cell Lung Cancer

et al. 2022

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“…The 0%，25%，50%，75%，100% methylation standards were prepared according to the sequence and preparation method in our previous study and the primers also used the same sequence from the previous study [ 13 ]. The HRM-qPCR experiment was performed on a LightCycler 96® real-time PCR system (Roche).…”

Section: Methodsmentioning

confidence: 99%

“…We previously identified that DNA methylation of the Interferon-induced protein 44-like ( I FI44L ) promoter region is markedly downregulated in SLE and could be used as a biomarker for SLE [ 12 ]. Then, we have reported a high-resolution melting-quantitative polymerase chain reaction (HRM-qPCR) to semi-quantitative analyze the methylation of IFI44L promoter, that can be used as a biomarker for the diagnosis of SLE with relative high sensitivity and specificity [ 13 ]. IFI44L gene is a stimulator of type I-IFN [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Difference of IFI44L methylation and serum IFN-a1 level among patients with discoid and systemic lupus erythematosus and healthy individuals

Zhang

Zhou

et al. 2021

Journal of Translational Autoimmunity

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Lupus erythematosus (LE) is an autoimmune disease that can be divided into two types. The cutaneous lupus erythematosus (CLE), such as discoid LE (DLE), affects only the skin. While the systemic lupus erythematosus (SLE) affects the hematopoietic, renal, and other systems. We previously found that IFI44L methylation could be a biomarker for SLE. Here, we detect the IFI44L methylation by high-resolution melting-quantitative polymerase chain reaction (HRM-qPCR) assay. The positive percentages of SLE, DLE and healthy controls (HC) are 96.00%, 27.45%, 2.00%, if the curve of 25% methylation was used as the threshold of SLE. And we determined the serum IFN-a1 level by enzyme-linked immunosorbent assay (ELISA) in SLE, DLE and HC. The serum concentration of IFN-a1 in patients with SLE was significantly higher than in the DLE (12.63 ± 6.38 pg/mL vs 7.99 ± 2.28 pg/mL, P < 0.05) and HC (12.63 ± 6.38 pg/mL vs 7.17 ± 1.86 pg/mL, P < 0.05). But the expression level of IFN-a1 in serum was not significantly different between DLE and HC (7.99 ± 2.28 pg/mL vs 7.17 ± 1.86 pg/mL, P = 0.5365). This suggests that methylation of IFI44L and serum concentration of IFN-a1 may be used as biomarkers to distinguish DLE from SLE.

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“…One of these genes is Interferon-induced protein 44-like (IFI44L). Although the exact function of this gene is unknown but studies demonstrated that expression of this gene is upregulated in SLE and RA patients which this upregulation was attributed to hypomethylation of IFI44L [21][22][23][24][25]. For the rst time, in two different studies, Chen and Zhao et al proposed that DNA methylation alteration of IFI44L is a promising biomarker for the diagnosis of SLE and RA with high speci city and sensitivity [24,26].…”

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confidence: 99%

IFI44L Gene Promoter is Differentially Methylated in Iranian Patients with Systemic Lupus Erythematosus and Rheumatoid Arthritis.

Salesi¹,

Mh²,

Salehi³

et al. 2021

Preprint

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Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are multisystemic autoimmune diseases with multifactorial nature. Considering limitations of the current conventional serological tests for diagnosis of these diseases, researchers strive to find new and more valid biomarkers. The methylation level of interferon-induced protein 44-like (IFI44L) promoter was evaluated in 69 patients with SLE, 61 patients with RA, and 71 healthy subjects. Quantitative methylation of the promoter region of IFI44L gene was measured in DNA extracted from peripheral blood mononuclear cells (PBMCs) with methylation-quantification endonuclease-resistant DNA (MethyQESD) method. Our findings revealed a substantial hypomethylation of IFI44L promoter in SLE and RA patients compared with healthy volunteers (mean: 60.36%±64.54%, 47.59%±30.34%, and 89.17%±76.96%, respectively; PSLE= 0.018, PRA<0.001). In comparison between SLE and RA patients with control group, IFI44L promoter methylation had a sensitivity of 84/06% and 93/65% and specificity of 32/39% and 29/58, respectively. The promoter methylation level was not meaningfully different between SLE and RA patients (P > 0.05). Moreover, our analysis revealed that the methylation level of IFI44L promoter was not statistically significantly different between SLE disease activity and renal involvements (P > 0.05). While RA patients with a higher concentration of CRP had a lower DNA methylation level (P = 0.012). The methylation level of IFI44L promoter was lower in PBMCs of Iranian patients with SLE and RA than that control group. Furthermore, DNA methylation level of IFI44L promoter had a negative correlation with RA disease activity. However, there was not a significant association between clinical characteristics of SLE.

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A simple and highly efficient method of IFI44L methylation detection for the diagnosis of systemic lupus erythematosus

Cited by 16 publications

References 22 publications

Comprehensive Analysis of Immune Implication and Prognostic Value of IFI44L in Non-Small Cell Lung Cancer

Comprehensive Analysis of Immune Implication and Prognostic Value of IFI44L in Non-Small Cell Lung Cancer

Difference of IFI44L methylation and serum IFN-a1 level among patients with discoid and systemic lupus erythematosus and healthy individuals

IFI44L Gene Promoter is Differentially Methylated in Iranian Patients with Systemic Lupus Erythematosus and Rheumatoid Arthritis.

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