Analysis Of Different Subtypes Research Articles

Correlation between the miR-618 rs2682818 C>A polymorphism and venous malformation susceptibility.

Venous malformations are the most common congenital vascular malformations, and the incidence rate is high. Previous studies have confirmed that a variety of polymorphisms within the miRNA functional region are associated with tumor susceptibility. We examined the correlation between miR-618 rs2682818 C>A and risk of developing venous malformation in a southern Chinese population (1113 patients and 1158 controls). TaqMan genotyping of miR-618 rs2682818 C>A was conducted utilizing real-time fluorescent quantitative PCR. The miR-618 rs2682818 polymorphism was not correlated with susceptibility to venous malformation (CA/AA vs. CC: adjusted odds ratio [AOR] = 1.00, 95% confidence interval [CI] = 0.81-1.25, p = 0.994; AA vs. CC/CA: AOR = 1.10, 95% CI = 0.73-1.65, p = 0.646). Stratified analysis of different subtypes of venous malformation revealed that there was no significant difference in the rs2682818 C>A polymorphism genotypes across these subtypes. Our results indicate that miR-618 rs2682818 C>A polymorphism is not correlated with the susceptibility to venous malformation.

Genetic analysis of different subtypes of aseptic pustulosis in the Chinese population.

Aseptic pustulosis involves inflammatory skin conditions with nonbacterial pustules on erythema, accompanied by neutrophil and eosinophil infiltration in the epidermis. Dysregulation of the interleukin (IL)-36 pathway leads to neutrophil aggregation and pustule formation. Variants in IL36RN, CARD14, AP1S3, MPO, SERPINA3 and BTN3A3 have been identified in generalized pustular psoriasis (GPP) in the past. Some patients with acrodermatitis continua of Hallopeau (ACH), palmoplantar pustulosis and acute generalized exanthematous pustulosis (AGEP) also exhibit mutations in IL36RN, CARD14 and AP1S3, albeit with regional and population-specific variations. This study aims to explore a shared genetic foundation among those with aseptic pustulosis. We performed Sanger sequencing on six genes in 126 patients with aseptic pustulosis. Genetic analysis identified IL36RN variants strongly associated with ACH, AGEP and subcorneal pustular dermatosis (SPD). Immunohistochemistry revealed elevated inflammatory cytokines in all subtypes. This study establishes a significant association between IL36RN variants and ACH, AGEP and SPD, emphasizing the IL-1/IL-36-chemokine-neutrophil axis as a common pathogenic mechanism. Targeting this axis holds promise for therapeutic interventions for aseptic pustulosis.

SERS and MRS signals engineered dual-mode aptasensor for simultaneous distinguishment of aflatoxin subtypes

The accurate monitoring of aflatoxin subtypes is vitally important for food safety. Herein, a dual-mode aptasensor with surface-enhanced Raman scattering (SERS) and magnetic relaxation switching (MRS) signals is developed for the detection of aflatoxin B1, B2 and M1 (i.e. AFB1, AFB2 and AFM1). Au-Ag Janus NPs and Au-mushroom NPs are prepared and show intense and non-interfering SERS peaks without the additional modification of Raman molecules, and are utilized as SERS nanotags for the distinguishment of AFB1 and AFB2. Fe3O4@Au NPs functionalized by AFM1 aptamers are applied as MRS nanoprobes for the monitoring of AFM1. Aptamers engineered SERS nanotags and MRS nanoprobes are assembled, and show strong SERS performances and high transverse relaxation time (T2). AFB1, AFB2 and AFM1 induce the separation of SERS nanotags from the assemblies and the dispersion of Fe3O4@Au NPs, resulting in the decrease of SERS signals at 1278 cm−1 and 1000 cm−1 as well as the reduction of T2 values. The dual-mode but three kinds of detection signals don’t interfere with each other and exhibit a significant linear relationship with the concentration of targets. This platform provides a high throughput monitoring strategy for the simultaneous analysis of different subtypes of mycotoxin.

Immune infiltration and drug specificity analysis of different subtypes based on functional status in angioimmunoblastic T-cell lymphoma

Angioimmunoblastic T-cell lymphoma (AITL) is a subtype of peripheral T-cell lymphoma (PTCL) strongly correlated with worse clinical outcomes. However, the role of characteristic pathway-related genes in patients with AITL (e.g., subtype typing and pathogenesis) remains unknown. In this study, we intended to understand the potential role and prognostic value of characteristic pathways in AITL and identified a model for subtype identification based on pathway-related functional status. Transcriptomic (RNA-seq) data were obtained from the Gene Expression Omnibus database for three sets of tumor tissues from AITL patients. AITL was divided into three clusters based on the pathway profile of patients and the best clustering k = 3, and differentially expressed genes (DEGs) in the three clusters were analyzed. The top 45 important variables associated with characteristic pathways, such as Huntington's disease, VEGF signaling pathway, nucleotide excision repair, ubiquitin-mediated proteolysis, purine metabolism, olfactory transduction, etc., were used to construct a subtype identification model. The model was experimentally validated and proved to possess good predictive efficacy. In addition, pathway-related subtype typing was significantly associated with different immune cell infiltration in AITL. Further analysis revealed that the drug IC50 values predicted also differed markedly among the different subtypes, thus further identifying some subtype-specific drugs. Our study indicates a potential role of characteristic pathways in AITL staging for the first time, provides novel insights for future research targeting AITL, and points to potential therapeutic options for patients with different subtypes of AITL.

Comparative 3-Sample 2D-DIGE Analysis of Skeletal Muscles.

The skeletal muscle proteome consists of a large number of diverse protein species with a broad and dynamic concentration range. Since mature skeletal muscles are characterized by a distinctive combination of contractile cells with differing physiological and biochemical properties, it is essential to determine specific differences in the protein composition of fast, slow, and hybrid fibers. Fluorescence two-dimensional difference gel electrophoresis (2D-DIGE) is a powerful comparative tool to analyze fiber type-specific differences between predominantly fast contracting versus slower twitching muscles. In this chapter, the application of the 2D-DIGE method for the comparative analysis of different subtypes of skeletal muscles is outlined in detail. A standardized proteomic workflow is described, involving sample preparation, protein extraction, differential fluorescence labeling using a 3-CyDye system, first-dimension isoelectric focusing, second-dimension slab gel electrophoresis, 2D-DIGE image analysis, protein digestion, and mass spectrometry.

The characteristics of intracranial plaques of unilateral, anterior circulation embolic stroke of undetermined source: An analysis of different subtypes based on high-resolution imaging.

The aim was to investigate the characteristics of non-stenotic intracranial plaque (NSIP) in embolic stroke of undetermined source (ESUS) subtypes by high-resolution magnetic resonance imaging. Consecutive patients with ESUS who were mandatory for high-resolution magnetic resonance imaging were retrospectively enrolled. Based on the location and arterial supply of the infarct, the ESUS were categorized into three types: cortical ESUS, subcortical ESUS and mixed ESUS. The NSIP parameters including plaque location, morphology (plaque distribution, remodeling index and plaque burden) and composition (thick fibrous cap, discontinuity of plaque surface, intraplaque hemorrhage and complicated plaque) were evaluated amongst the subtypes. Of 243 patients, there were 87 (35.8%) cortical ESUS, 127 (52.3%) subcortical ESUS and 29 (11.9%) mixed ESUS. Significant differences were found in plaque location (p < 0.001), plaque quadrant (p < 0.001), remodeling index (p < 0.001), plaque burden (p < 0.001), discontinuity of plaque surface (p < 0.001), intraplaque hemorrhage (p=0.001) and complicated plaque (p < 0.001) of ipsilateral NISP amongst the different ESUS subtypes, except for fibrous cap (p=0.135). However, no differences were found amongst contralateral NISP. In addition, the clinical characteristics of the differences between ESUS subtypes were striking, including age (p=0.004), initial National Institutes of Health Stroke Scale (p < 0.001), coronary artery disease (p=0.039), serum urea (p=0.011) and creatinine (p=0.002). This is the first report of significantly heterogeneous characteristics of ipsilateral NSIP and clinical findings amongst ESUS subtypes, which may suggest their different underlying mechanisms.

Hypoxia Contributes to Poor Prognosis in Primary IDH-wt GBM by Inducing Tumor Cells MES-Like Transformation Trend and Inhibiting Immune Cells Activity.

AimsTo reveal the influence of hypoxia on tumor cells and immune cells in primary IDH-wt glioblastoma patients.MethodsSingle-cell RNA-seq data and bulk RNA-seq data were acquired from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases, respectively. Hypoxia status and subtypes of tumor cells were identified based on single-sample Gene Set Enrichment Analysis (ssGSEA). Regulon network analysis of different subtypes under different conditions was conducted by SCENIC. Within tumor microenvironment, biological process activity analysis and cell–cell communication network were conducted to uncover the inner links between each cell subtype under different hypoxia status.ResultsDifferent types of tumor cell in GBM possessed different hypoxia status, and MES-like subtype was under a more severe hypoxia condition than other subtypes. Hypoxia also induced MES-like signature gene expression within each tumor cell, which could stimulate tumor cell proliferation and invasion by regulating cell–cell communication. Additionally, hypoxia inhibited immune cell activity in the tumor microenvironment by inducing macrophage phenotype polarization and upregulating immune-inhibited cell–cell interaction within immune cells. Interactions between tumor cells and immune cells under hypoxia status also promoted tumor progression.ConclusionsHypoxia was a poor prognostic marker for primary IDH-wt GBM patients. Meanwhile, it could induce tumor cells’ MES-like transformation trend and inhibit antitumor function of immune cells.

Developing metabolic gene signatures to predict intrahepatic cholangiocarcinoma prognosis and mining a miRNA regulatory network.

BackgroundMetabolic disturbance is closely correlated with intrahepatic cholangiocarcinoma (IHCC), and we aimed to identify metabolic gene marker for the prognosis of IHCC.MethodsWe obtained expression and clinical data from 141 patients with IHCC from public databases. Prognostic metabolic genes were selected using univariate Cox regression analysis. Unsupervised cluster analysis was applied to identify IHCC subtypes, and CIBERSORT was used for immune infiltration analysis of different subtypes. Then, the metabolic gene signature was screened using multivariate Cox regression analysis and the LASSO algorithm. The prognostic potential and regulatory network of the metabolic gene signature were further investigated.ResultsWe screened 228 prognosis‐related metabolic genes. Based on their expression levels, IHCC samples were divided into two subtypes, which showed significant differences in survival and immune cell infiltration. After LASSO analysis, eight metabolic genes including CYP19A1, SCD5, ACOT8, SRD5A3, MOGAT2, PFKFB3, PPARGC1B, and RPL17 were identified as the optimal genes for the prognosis signature. The prognostic model had excellent predictive abilities, with areas under the receiver‐operating characteristic curves over 0.8. A nomogram model was also established based on two independent prognostic clinical factors (pathologic stage and prognostic model), and the generated calibration curves and c‐indexes determined its excellent accuracy and discriminative ability to predict 1‐ and 5‐year survival status (c‐indexes>0.7). Finally, we found that miR‐26a‐5p, miR‐27a‐3p, and miR‐27b‐3p were the upstream regulators that mediate the involvement of gene signatures in metabolic pathways.ConclusionWe developed eight metabolic gene signatures to predict IHCC prognosis and proposed potential upstream regulatory axes of gene signatures.

Ultrasonic and pathological comparative analysis of different subtypes of breast encapsulated papillary carcinoma

Objective: To investigate the clinicopathological and ultrasonic characteristics of patients with breast encapsulated papillary carcinoma (EPC) and the comparative analysis of different subtypes. Methods: A total of 57 patients with pathological diagnosis of breast EPC in the First Affiliated Hospital of Nanjing Medical University from September 2014 to August 2020 were retrospectively collected. Based on pathological diagnosis, patients were divided into 3 subtypes, and their clinical, pathological and ultrasonic manifestations were compared and analyzed. Results: Among the enrolled patients, there were 2 males and 55 females, aged 41-88 (63±11) years. The lesion diameter of EPC was 7.0-7.5 (2.9±1.9) cm. There were 16 cases of simple EPC, 9 cases of EPC with ductal carcinoma in situ (DCIS), and 32 cases of EPC with infiltration. The molecular classification was mainly luminal (55/57, 96.6%), of which 38 cases were Luminal A type and 17 cases were Luminal B type. The majority ultrasound images of EPC showed nodules with size greater than 2 cm (68.4%), regular morphology (64.9%), edge finishing (54.4%), no burr forming angles (82.5%), and no calcification (93%). There were differences between different subtypes. The simple EPC was closer to the nipple than the EPC with infiltration, with regular shape and smooth edge (P<0.05). Compared with the EPC with DCIS, the EPC with infiltration had richer blood flow and was farther away from the nipple (P<0.05). There was no significant difference between the simple EPC and the EPC with DCIS (P>0.05). Conclusion: The simple EPC often showed benign signs on ultrasound, such as regular morphology, smooth edge, and cystic-solid internal structure. If the distance between the lesion and the nipple was greater than 3 cm, the shape was irregular, and the edge was blurred, the possibility of EPC with infiltration was high. Multi-modality image fusion was helpful for accurate diagnosis and treatment of EPC.

Phylogenetic analysis of canine parvovirus 2 subtypes from diarrheic dogs in Iran.

Canine parvovirus type 2 (CPV-2) causes gastroenteritis and leukopenia in dogs worldwide. They are three subtypes of CPV-2 including CPV-2a, CPV-2b, and CPV-2c. The distribution status of CPV-2 subtypes has been shown differences in many countries. The aim of the present study was detection and phylogenetic analysis of different subtypes of CPV-2 circulating in two provinces of Iran, Tehran and Alborz. CPV-2 was detected using 555 primer pairs in collected samples. Phylogenetic analysis of CPV-2 subtypes was done using sequencing of the partial length of VP2 gene. Twenty-eight CPV-2 were detected using 555 primer pair. The sequences of isolates were deposited in the GenBank database. Phylogenetic analysis revealed that all CPV-2c subtype isolates had very high sequence identity to China and Zambia that form a distinct cluster. In conclusion, this study revealed the emergence of all CPV-2 variants in dogs in Iran. Thus, the continual monitoring of CPV-2 in domestic dogs should be further conducted on a large scale to determine the predominant variants and their distributions in the country and to follow the dynamics of CPV-2 in the Middle East region of Asia.

Comprehensive Network Analysis of Different Subtypes of Molecular Disorders in Lung Cancer

Comprehensive Network Analysis of Different Subtypes of Molecular Disorders in Lung Cancer

Systematic identification of lncRNA-based prognostic biomarkers for glioblastoma.

Glioblastoma (GBM), a primary malignant tumor of the central nervous system, has a very poor prognosis. Analysis of global GBM samples has revealed a variety of long non-coding RNAs (lncRNAs) associated with prognosis; nevertheless, there remains a lack of accurate prognostic markers. Using RNA-Seq, methylation, copy number variation (CNV), mutation and clinical follow-up data for GBM patients from The Cancer Genome Atlas, we performed univariate analysis, multi-cluster analysis, differential analysis of different subtypes of lncRNA and coding genes, weighted gene co-expression network analyses, gene set enrichment analysis, Kyoto Encyclopedia of Genes and Genomes analysis, Gene Ontology analysis, and lncRNA CNV analyses. Our analyses yielded five lncRNAs closely related to survival and prognosis for GBM. To verify the predictive role of these five lncRNAs on the prognosis of GBM patients, the corresponding RNA-seq data from Chinese Glioma Genome Atlas were downloaded and analyzed, and comparable results were obtained. The role of one lncRNA LINC00152 has been observed previously; the others are novel findings. Expression of these lncRNAs could become effective predictors of survival and potential prognostic biomarkers for patients with GBM.

Comparative 3-Sample DIGE Analysis of Skeletal Muscles.

The skeletal muscle proteome consists of a large number of diverse protein species with a broad and dynamic concentration range. Since mature skeletal muscles are characterized by a specific combination of contractile cells with differing physiological and biochemical properties, it is essential to determine specific differences in the protein composition of fast, slow, and hybrid fibers. Fluorescence two-dimensional gel electrophoresis (DIGE) is a powerful comparative tool to analyze fiber type-specific differences between fast and slow muscles. In this chapter, the application of the DIGE method for the comparative analysis of different subtypes of skeletal muscles is outlined in detail. A standardized proteomic workflow is described, involving sample preparation, protein extraction, differential fluorescence labeling using a 3-dye system, first-dimension isoelectric focusing, second-dimension slab gel electrophoresis, DIGE image analysis, protein digestion, and mass spectrometry.

Clinical features and survival analysis of different subtypes of patients with breast cancer brain metastases

The brain is one of the most common metastatic sites of breast cancer. Brain metastases develop in 10%-15% of patients with breast cancer and are associated with poor prognosis. The purpose of this retrospective study was to analyze the clinical characteristics and survival of patients with brain metastases due to breast cancer of different subtypes and to identify the prognostic factors that affect clinical outcome. A total of 89 patients with breast cancer brain metastases diagnosed between October 1997 and July 2008 at Sun Yat-sen University Cancer Center were included in this study. Among the 89 patients, the number of luminal A, luminal B, human epidermal growth factor receptor 2 (HER-2), and triple-negative (TN) subtypes were 30, 20, 16, and 14, respectively; 9 patients had an unknown subtype. The clinical characteristics, pathologic features, and prognostic factors were analyzed both at the initial diagnosis and at the diagnosis of brain metastases. Endocrine therapy for patients with luminal subtypes was further studied. The median age of patients was 46 years (range 28-74 years). The median survival time was 8.0 months (range, 0-80 months), the 1-year survival rate was 32% and the 5-year survival rate was 4%. The time to brain metastasis differed according to clinical stage at the initial diagnosis, and the time for patients with the luminal A subtype was the longest (P < 0.001). Multivariate analysis demonstrated that performance status score > 1, multiple brain metastases and without whole brain radiotherapy (WBRT) in combination with chemotherapy were associated with poor prognosis. Compared with the luminal A subtype, features of the HER-2 and TN subtypes included early metastases, rapid progression after first-line treatment (8.0 months vs. 11.0 months), and poor overall survival (25.0 months vs. 63.0 months). The luminal A subtype showed a tendency for good prognosis and slow growth. Tamoxifen could improve the survival of luminal A/B subtypes (median survival 24.0 months vs. 7.0 months, respectively, P = 0.002). The prognosis of brain metastases from breast cancer was poor, especially in patients with HER-2 and TN subtypes. Generally, WBRT in combination with chemotherapy was the standard treatment modality. Patients with the luminal subtypes could benefit from tamoxifen.

Proteomic analysis of acute myeloid leukemia: Identification of potential early biomarkers and therapeutic targets

The main goal of this study was to analyze, using proteomic techniques, changes in protein expression of acute myeloid leukemia (AML) cells that could give insights into a better early prognosis for tumor pathophysiology. Proteomic analysis of different subtypes of AML cells was carried out using 2-DE and MALDI-TOF PMF analysis. Proteins identified as more significantly altered between the different AMLs belonged to the group of suppressor genes, metabolic enzymes, antioxidants, structural proteins and signal transduction mediators. Among them, seven identified proteins were found significantly altered in almost all the AML blast cells analyzed in relation to normal mononuclear blood cells: alpha-enolase, RhoGDI2, annexin A10, catalase, peroxiredoxin 2, tromomyosin 3, and lipocortin 1 (annexin 1). These differentially expressed proteins are known to play important roles in cellular functions such as glycolysis, tumor suppression, apoptosis, angiogenesis and metastasis, and they might contribute to the adverse evolution of the disease. Proteomic analysis has identified for the first time novel proteins that may either help to form a differential prognosis or be used as markers for disease outcome, thus providing potential new targets for rational pathogenesis-based therapies of AML.