Ask about this productRelated genes to: IFIH1 Blocking Peptide
- Gene:
- IFIH1 NIH gene
- Name:
- interferon induced with helicase C domain 1
- Previous symbol:
- -
- Synonyms:
- MDA-5, Hlcd, MDA5, IDDM19
- Chromosome:
- 2q24.2
- Locus Type:
- gene with protein product
- Date approved:
- 2004-06-25
- Date modifiied:
- 2019-04-23
Related products to: IFIH1 Blocking Peptide
Related articles to: IFIH1 Blocking Peptide
- Prostate adenocarcinoma is characterized by substantial inter-patient heterogeneity, limiting the clinical reliability of conventional diagnostic tools, including prostate-specific antigen testing. This limitation underscores the need for robust molecular biomarkers that may complement conventional diagnostic tools, highlighting the urgent need for biomarkers capable of enhancing diagnostic accuracy and enabling more precise risk stratification. In the present study, transcriptomic data from The Cancer Genome Atlas (TCGA) were analyzed using an integrative bioinformatics and machine learning pipeline., The proposed workflow was designed as a stepwise and reproducible biomarker prioritization framework in which differential expression analysis, functional enrichment, protein-protein interaction (PPI) based network interpretation, graph-convolutional feature selection, and hybrid ensemble machine learning were sequentially integrated. Differential gene expression analysis was combined with pathway enrichment (Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome), protein-protein interaction network construction, and graph-convolutional feature selection. Multiple machine learning algorithms, including Random Forest, Gradient Boosting Machine, Support Vector Classifier, Artificial Neural Network, and AdaBoost, were systematically evaluated. A hybrid ensemble model integrating Gradient Boosting Machine and Random Forest (GBM+RF) was subsequently developed. Model performance was assessed using accuracy, sensitivity, specificity, and area under the Receiver Operating Characteristic (ROC) and externally validated using the independent GSE14206 dataset. The analysis revealed a coordinated molecular pattern characterized by dysregulated cell cycle activity and enhanced interferon-mediated immune signaling. Protein-protein interaction analysis identified and as highly connected network hub genes within immune-related and cell-cycle-associated modules. Among the evaluated models, the hybrid GBM+RF framework achieved the highest predictive performance on the TCGA dataset, with AUC: 0.9526; Accuracy: 97.49%. External validation using the GSE14206 dataset confirmed the robustness of this model (AUC: 0.9156; Accuracy: 91.53%). These findings support a broader multi-gene candidate signature in prostate adenocarcinoma, in which machine learning prioritized genes such as , , , , , , , and , while and provided complementary network-level biological relevance. The proposed framework provides a robust and transferable strategy for biomarker discovery and precision oncology. - Source: PubMed
Publication date: 2026/07/25
Kurt Hasan AnılKılıçarslan SabireÇiçekliyurt Meliha MerveKılıçarslan Serhat - Multiple myeloma (MM) remains an incurable hematological malignancy in which tumor-intrinsic immune evasion limits the efficacy of immunotherapy. Here, we identify the RNA editing enzyme ADAR1 as a key regulator of innate immune suppression in MM. Integrative analyses of bulk and single-cell transcriptomic datasets, together with clinical validation, demonstrated that ADAR1 is upregulated in malignant plasma cells and is associated with adverse clinical outcomes and reduced CD8 T-cell infiltration. Mechanistically, ADAR1 knockdown increased the association of endogenous dsRNA with melanoma differentiation-associated protein 5 (MDA5), restoring type I interferon (IFN) signaling, enhancing IFNα production and STAT1 activation, and promoting CD8 T-cell proliferation and cytotoxic function. These effects were largely abolished by MDA5 depletion, establishing a functional ADAR1-MDA5 signaling axis in MM. In vivo, treatment with 8-azaadenosine significantly potentiated the antitumor efficacy of PD-1 blockade, resulting in reduced tumor growth, increased tumor cell apoptosis, elevated IFNα expression, and enhanced CD8 T-cell infiltration. Together, our findings demonstrate that ADAR1-mediated RNA editing enables immune evasion by restricting MDA5-dependent sensing of endogenous dsRNA and highlight the ADAR1-MDA5-type I interferon axis as a promising therapeutic target for improving immunotherapy in multiple myeloma. - Source: PubMed
Publication date: 2026/07/24
Leng SongzeTian YaoyaoLiu YaoZhao WeiweiWang Wei - To explore the clinical characteristics, efficacy and safety of different therapeutic regimens in patients with anti-MDA5 antibody positive dermatomyositis (anti-MDA5⁺DM) stratified by disease risk, and to analyze the influencing factors for prognosis. This was a retrospective cross-sectional study. Clinical data of 82 patients with anti-MDA5⁺DM admitted to the First Affiliated Hospital of Guangxi Medical University from January 2018 to June 2024 were retrospectively analyzed. All patients were stratified into low-risk group and intermediate-high-risk group based on the FLAIR model, a predictive model for mortality risk in amyopathic dermatomyositis combined with interstitial lung disease. Meanwhile, patients were divided into four groups according to treatment regimens: Regimen A: glucocorticoids combined with calcineurin inhibitors and cyclophosphamide; Regimen B: glucocorticoids combined with Janus kinase inhibitors with or without calcineurin inhibitors; Regimen C: glucocorticoids combined with calcineurin inhibitors; Regimen D: glucocorticoids combined with cyclophosphamide. The clinical manifestations, laboratory parameters, infection events and survival outcomes were compared among groups with different risk stratification and different treatment regimens. Multivariate logistic regression analysis was performed to identify clinical indicators independently associated with all-cause mortality. Among the 82 patients with anti-MDA5⁺DM, 19 (23.2%) were males and 63 (76.8%) were females, with a median age of 50 years (range, 37-63 years). The incidence of cough was higher in the intermediate-high risk group [44 cases (74.6%)] than that in the low-risk group [10 cases (43.5%)] (²=7.12, =0.008). The intermediate-high risk group also exhibited higher frequencies of expectoration [35 cases (59.3%) vs. 7 cases (30.4%), ²=5.53, =0.019], dyspnea [37 cases (62.7%) vs. 8 cases (34.8%), ²=5.21, =0.022] and fever [36 cases (61.0%) vs. 6 cases (26.1%), ²=8.08, =0.004]. Median serum ferritin level was 1 545.3 (936.8, 2 376.9) μg/L in the intermediate-high risk group versus 442.8 (138.9, 759.0) μg/L in the low-risk group (=-4.89, <0.001). The intermediate-high risk group had significantly elevated median levels of lactate dehydrogenase [371.0 (302.0, 473.0) vs. 242.0 (208.0, 318.0) U/L, =-4.95, <0.001], creatine kinase [87.0 (60.0, 254.0) vs. 45.0 (34.0, 113.0) U/L, =-2.83, =0.005], carcinoembryonic antigen [6.8 (3.2, 12.5) vs. 3.8 (2.4, 6.0) μg/L, =-2.32, =0.021], aspartate aminotransferase [74.0 (47.0, 133.0) vs. 45.0 (31.0, 55.0) U/L, =-3.44, =0.001], C-reactive protein [7.6 (2.6, 16.3) vs. 2.4 (0.7, 5.0) mg/L, =-3.24, =0.001] and erythrocyte sedimentation rate [42.0 (23.8, 63.5) vs. 23.0 (13.0, 34.0) mm/1 h, =-3.36, =0.001].The prevalence of periorbital edematous erythema was significantly lower in the intermediate-high risk group [29 cases (49.2%)] compared with the low-risk group [17 cases (73.9%)] (²=4.12, =0.042). The median immunoglobulin M level was markedly decreased in the intermediate-high risk group [1.2 (0.9, 1.6) g/L] relative to the low-risk group [1.7 (1.2, 2.8) g/L] (=-2.66, =0.008).Complete follow-up data were obtained from 78 patients. The all-cause mortality rate (13.0% vs. 38.2%) and infection rate (6.7% vs. 57.1%) of the low-risk group were obviously lower than those of the intermediate-high-risk group. Within each risk stratum, there was no statistically significant difference in the incidence of severe infections among the four treatment regimens. Regimen A was associated with the highest survival rate among patients in the intermediate-high-risk group. Taking Regimen A as the reference, Regimens B, C and D were correlated with higher mortality risk, with corresponding values as follows: Regimen B =0.07 (95% 0.01-0.43, =0.002), Regimen D =0.07 (95% 0.01-0.62, =0.008), Regimen C =0.06 (95% 0.01-0.41, =0.001).Multivariate logistic regression analysis revealed that rapidly progressive interstitial lung disease (RP-ILD) and dysphagia were independently correlated with mortality outcomes: RP-ILD (=24.95, 95% 1.47-422.55, =0.026), dysphagia (=11.62, 95% 1.23-110.15, =0.033). Positive anti-Ro52 antibody (=6.40, 95% 0.90-45.47, =0.063) and elevated C-reactive protein (=1.04, 95% 0.99-1.10, =0.091) showed a trend toward higher mortality risk. In patients with intermediate-high-risk anti-MDA5⁺DM, inflammatory biomarkers and clinical symptoms were positively associated with adverse mortality outcomes. RP-ILD and dysphagia were independently correlated with all-cause mortality. Among intermediate-high-risk patients, the regimen combining glucocorticoids, calcineurin inhibitors and cyclophosphamide was associated with higher survival probability, without an increased incidence of severe infections. - Source: PubMed
Xu X DMo H YZhao CWen JZheng L TQin FLei L - Dermatomyositis-associated interstitial lung disease (DM-ILD) is a life-threatening condition that often leads to respiratory failure, poor prognosis, and high mortality, especially in patients positive for anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibodies. Early identification of MDA5 positivity is crucial for timely intervention, yet routine testing is not consistently available across different regions. In some centers, the test is omitted or sent to external laboratories, which can delay recognition of disease severity and postpone appropriate treatment. Because risk assessment based on admission data remains limited, we focused on 90-day respiratory failure as an early and clinically relevant outcome, collecting patients' clinical information within the first 48 hours of admission while excluding anti-MDA5 results. Using these data, we developed and internally tested a multimodal model to predict 90-day respiratory failure in patients with DM-ILD. - Source: PubMed
Publication date: 2026/07/16
Guo LihuiYao YaningWu QiruiWang HuiNiu CaiyunWang GangChen Fei - Breast cancer (BC) is the most commonly diagnosed malignant disease in women worldwide. Resistance to neoadjuvant chemotherapy (NAC) still limits treatment efficacy despite the enormous progress in systemic therapy. Because pathological complete response (pCR) is strongly associated with favorable clinical outcomes, especially in triple-negative and HER2-positive breast cancer, the discovery of reliable predictive biomarkers before treatment has become a key clinical goal. This narrative review summarizes the available evidence of genetic and transcriptomic biomarkers associated to responses to conventional anthracycline, taxane and platinum-based NAC. Current evidence suggests biomarkers can be broken down into three interconnected biological pathways. Dysregulation of immune and interferon signaling, including interferon-stimulated genes (ISG15, IFIH1, MX1, OAS family, IFI27, and IFITM1), affects chemotherapy response by modulating immune activation, apoptosis, and DNA damage tolerance. Second, alterations in DNA damage response (DDR) pathways for BRCA1, TP53, PARP1, ATM, and CHK1 affect the cells' vulnerability to genotoxic stress and contribute to the subtype-specific differences in treatment efficacies. Third, dysregulated cell cycle components (CCND1, CDK4/6, RB1, and E2F1) affect proliferation, checkpoint control, and susceptibility to chemotherapy-induced apoptosis. These pathways act in concert, rather than as independent mechanisms, to influence NAC sensitivity. Available data suggest that no single biomarker has sufficient predictive accuracy for all breast cancer subtypes. Subtype-specific multi-gene models integrating immune, DDR and cell-cycle biomarkers represent a more powerful tool to predict pCR and improve patient stratification before NAC. Further prospective clinical validation is needed before these biomarkers can be implemented in routine clinical practice. - Source: PubMed
Publication date: 2026/07/30
Ahdi DanialHashemi SolmazGholami AysanDerakhshan Sima Mansoori