Psoriasis is a chronic, immune-mediated and inflammatory skin disease. Although various biological drugs are available for psoriasis treatment, some patients have poor responses or do not respond to treatment. The aim of the present study was to highlight the molecular mechanism of responsiveness to current biological drugs for psoriasis treatment. To this end, we reviewed previously published articles that reported genes associated with treatment response to biological drugs in psoriasis, and gene ontology analysis was subsequently performed using the Cytoscape platform. Herein, we revealed a statistically significant association between NF-kappaB signaling (p value = 3.37 × 10⁻⁹), regulation of granulocyte macrophage colony-stimulating factor production (p value = 6.20 × 10⁻⁶), glial cell proliferation (p value = 2.41 × 10⁻⁵) and treatment response in psoriatic patients. To the best of our knowledge, we are the first to directly associate glial cells with treatment response. Taken together, our study revealed gene ontology (GO) terms, some of which were previously shown to be implicated in the molecular pathway of psoriasis, as novel GO terms involved in responsiveness in psoriatic disease patients.

Background: Breast cancer (BC) comprises multiple subtypes with distinct molecular features, which differ in their interplay with host immunity, prognosis, and treatment. Non-invasive blood analyses can provide valuable insights into systemic immunity during cancer. The aim of this study was to analyze the expression of transcriptional isoforms in peripheral blood mononuclear cells (PBMCs) from BC patients and healthy women to identify potential BC immune biomarkers. Methods: RNA sequencing and isoform-level bioinformatics were performed on PBMCs from 12 triple-negative and 13 luminal A patients. Isoform expression validation by qRT-PCR and clinicopathological correlations were performed in a larger cohort (156 BC patients and 32 healthy women). Results: Transcriptional analyses showed a significant (p < 0.001) decrease in the ENST00000374459 RASGEF1A isoform in PBMCs of BC compared to healthy subjects, indicating disease-related expression changes. The decrease was associated with higher ctDNA and Ki-67 values. Conclusions: The levels of the RASGEF1A transcriptional isoform ENST00000374459 may have the potential to distinguish between BC and healthy subjects. The downregulation of ENST00000374459 in breast cancer is associated with higher proliferation and ctDNA shedding. Specialized bioinformatics analyses such as isoform analyses hold significant promise in the detection of biomarkers, since standard RNA sequencing analyses may overlook specific transcriptional changes that may be disease-associated and biologically important.

Curated online interaction databases and gene ontology tools have streamlined the analysis of highly complex gene/protein networks. However, understanding of disease pathogenesis has gradually shifted from a protein-based core to complex interactive networks where non-coding RNA (ncRNA) is thought to play an essential role. As current gene ontology is based predominantly on protein-level information, there is a growing need to analyze networks with ncRNA. In this study, we propose a gene ontology workflow integrating ncRNA using the NPInter V5.0 database. To validate the proposed workflow, we analyzed our previously published curated biomarker datasets for hidden disease susceptibility processes and pharmacogenomics. Our results show a novel involvement of melanogenesis in psoriasis response to biological drugs in general. Hyperpigmentation has been previously observed in psoriasis following treatment with currently indicated biological drugs, thus calling attention to melanogenesis research as a response biomarker in psoriasis. Moreover, our proposed workflow highlights the need to critically evaluate computed ncRNA interactions within databases and a demand for gene ontology analysis of large miRNA blocks.

Crohn’s disease is a consequence of dysregulated inflammatory response to the host’s microbiota. Although anti-TNF treatment improves the quality of the patient’s life, a large proportion of patients lose response to the treatment. The past decade of research has led to a continuum of studies showcasing the heterogeneity of anti-TNF response; thus, the aim of the present study was to dissect transcriptome-wide findings to transcript isoform specific levels and combine the analyses with refined information of immune cell landscapes in colon tissue, and subsequently select promising candidates using gene ontology and genomic integration. We enrolled Slovenian Crohn’s disease patients who were naïve with respect to adalimumab treatment. We performed colon tissue RNA sequencing and peripheral blood mononuclear cell DNA genotyping with a subsequent contemporary integrative approach to combine immune cell deconvoluted isoform transcript specific transcriptome analysis, gene ontology layering and genomic data. We identified nine genes (MACF1, CTSE, HDLBP, HSPA9, HLA-DMB, TAP2, LGMN, ANAPC11, ACP5) with 15 transcripts and 16 variants involved in the adalimumab response. Our study identified loci, some of which were previously shown to contribute to inflammatory bowel disease susceptibility, as novel loci involved in adalimumab response in Crohn’s disease patients.

Background/Objectives: Psoriasis is a chronic immune-mediated skin disease, with plaque psoriasis being its most prevalent form. Although biologic therapies have significantly improved outcomes for patients with moderate to severe disease, certain anatomical regions often remain resistant to treatment. Given the observed variability in treatment response depending on lesion location, we aimed to explore anatomical site-specific differences in the skin transcriptome. Methods: Using a non-invasive tape-stripping technique, we collected and analyzed 44 psoriatic plaque samples from the scalp, trunk, upper extremities, and lower extremities, followed by differential gene expression and gene ontology analysis. Moreover, we included 80 samples obtained from healthy skin biopsies (GSE54456) to conduct an inflammation-controlled approach. We used two different approaches, an intra-disease approach, in which anatomically different sites were compared, and an inflammation-controlled approach, in which the inflammation bias was reduced. Results: Our findings indicate distinct molecular signatures and biological pathways across different anatomical sites, including differential expression of SERPINB7 and miRNAs such as miR-205 and miR-203a, along with different pathways. Furthermore, our results emphasized the heterogeneity of psoriasis and suggested that site-specific molecular mechanisms may contribute to variations in disease manifestation and treatment response. Conclusions: This study highlights the need for more personalized, site-specific therapeutic strategies. It should be considered an exploratory pilot study, and larger studies with paired samples from multiple anatomical sites within the same patients are needed to validate the identified transcriptomic signatures.

Atopic dermatitis (AD) is among the most common chronic inflammatory diseases. Due to the heterogeneous presentation of AD, patient response to treatment may differ considerably. Therefore, there is a pressing need for biomarkers associated with response to biological therapies. Thus, we aimed to identify blood-based candidate biomarkers associated with response in patients treated with dupilumab. The present study applied a multi-stage integrative analytical framework combining transcriptomic profiling, functional enrichment, co-expression network analysis, and genomic variant analysis to identify potential biomarkers. Eighteen dupilumab-naïve patients were enrolled in the transcriptomic analysis, with blood samples collected at baseline and after 16–18 weeks of therapy; five patients were identified as non-responders. Additionally, genotyping was performed in 34 patients. We identified a set of candidate genes (RPL18A, RPS28, FAU, MASTL, AURKA, TAF2, BUB1B, and RNF135) and genomic variants that may reflect underlying biological mechanisms influencing therapeutic response. However, given the limited sample size, these findings should be considered exploratory and hypothesis-generating. Finally, our study identified exploratory candidate genes potentially associated with variability in dupilumab treatment response. Moreover, our study represents an incremental contribution to existing knowledge, opening avenues for research that may ultimately lead to personalized medicine.