The immune system plays a critical role in inflammation by initiating responses to infections or tissue damage. The nuclear factor-κB (NF-κB) pathway plays a key role in inflammation and innate immunity, as well as other cellular activities. Dysregulation of this well-choreographed pathway has been implicated in various diseases, including cancer. CARD11 is a key molecule in the BCL10-MALT1 complex, which is involved in transducing the signal downstream of the NF-κB pathway. This study aims to elucidate how CARD11 overexpression exacerbates the prognosis of colorectal cancer (CRC). To identify the cellular pathways influenced by CARD11, transcriptomic analysis in both CRC cell lines and patients was carried out on CARD11– overexpressed HCT-116 and HT-29 CRC cell lines alongside empty vector-transfected cell lines. Furthermore, a comparison of transcriptomic data from adenoma and carcinoma CRC patients with low- (CARD11–) and high-(CARD11+) CARD11 expression was carried out. Whole transcriptomics and bioinformatics analysis results indicate that CARD11 appears to play a key role in CRC progression. Absolute GSEA (absGSEA) on HCT-116 transcriptomics data revealed that CARD11 overexpression promotes cell growth and tissue remodeling and enhances immune response. Key genes co-expressed with CARD11, such as EP300, KDM5A, HIF1A, NFKBIZ, and DUSP1, were identified as mediators of these processes. In the HT-29 cell line, CARD11 overexpression activated pathways involved in chemotaxis and extracellular matrix (ECM) organization, marked by IL1RN, MDK, SPP1, and chemokines like CXCL1, CXCL3, and CCL22, which were shown to contribute to the more invasive stage of CRC. In patient samples, adenoma patients exhibited increased expression of genes associated with the tumor immune microenvironment, such as IL6ST, collagen family members, and CRC transition markers, such as GLI3 and PIEZO2, in CARD11+ adenoma patients. Carcinoma patients showed a dramatic increase in the expression of MAPK8IP2 in CARD11+ carcinoma patients alongside other cancer-related genes, including EMB, EPHB6, and CPEB4.

Focal segmental glomerulosclerosis (FSGS) is a major cause of nephrotic syndrome and often leads to progressive kidney failure. Its varying clinical presentation suggests potential genetic diversity, requiring further molecular investigation. This study aims to elucidate some of the genetic and molecular mechanisms underlying FSGS. The study focuses on the use of bioinformatic analysis of gene expression data to identify genes associated with familial FSGS. A comprehensive in silico analysis was performed using the GSE99340 data set from Gene Expression Omnibus (GEO) comparing gene expression in glomerular and tubulointerstitial tissues from FSGS patients (n = 10) and Minimal Change Disease (MCD) patients (n = 8). These findings were validated using transcriptomics data obtained using RNA sequencing from FSGS (n = 3) and control samples (n = 3) from the UAE. Further validation was conducted using qRT-PCR on an independent FFPE cohort (FSGS, n = 6; MCD, n = 7) and saliva samples (FSGS, n = 3; Control, n = 7) from the UAE. Three genes (TUBB6, RPL27, and PFDN5) showed significant differential expression (p < 0.01) when comparing FSGS and MCD with healthy controls. These genes are associated with cell junction organization and synaptic pathways of the neuron, supporting the link between FSGS and the neural system. These genes can potentially be useful as diagnostic biomarkers for FSGS and to develop new treatment options.

Background: Prostate cancer (PC) is a heterogeneous disease in which the histopathological grade does not always reflect underlying biological behavior. While transcriptomic studies have provided insight into tumor biology, grade-associated molecular changes remain incompletely defined, particularly in underrepresented populations such as those from the Middle East and North Africa (MENA) region. Methods: In this study, we used a pathology-guided transcriptomic approach to examine gene expression patterns across PC grades in a MENA cohort. RNA sequencing was performed on formalin-fixed paraffin-embedded (FFPE) tissues, including benign prostatic hyperplasia (BPH, n = 7), low-grade tumors (Gleason 6–7 [3 + 4]; LG; n = 7), and high-grade tumors (Gleason 7 [4 + 3]–10; HG; n = 7). Differential expressions, pathway-level enrichment analyses and the estimation of immune cell composition were carried out, followed by comparison with publicly available datasets (TCGA-PRAD, n = 496), including LG tumors (n = 292) and HG tumors (n = 204), using the GEPIA2 and UALCAN platforms. Selected genes were further assessed using qRT-PCR in an independent set of samples (n = 21). Representative immunohistochemical images from the Human Protein Atlas were reviewed to provide descriptive protein-level context across tumor grades. Results: Transcriptomic comparisons of tumor samples with benign controls identified a set of shared transcriptional changes present in both low- and high-grade disease. Among these, SLC29A2 and IL2RA showed consistent upregulation across tumor grades and similar expression trends in external datasets. Direct comparison between HG and LG tumors revealed distinct transcriptional profiles with patterns indicative of increased proliferative activity and altered immune-related signaling in higher-grade disease. Pathway-level analyses showed the enrichment of cell-cycle and metabolic gene signatures in HG tumors, whereas inflammatory and NF-κB-associated transcriptional signatures showed a comparatively reduced expression. Additional genes, including AAMDC, ASAH2, TNFRSF1B, NFKBIL1, and NFKBIZ, were associated with these grade-dependent differences. qRT-PCR findings were generally consistent with the RNA-seq results for selected targets. Conclusions: This study describes transcriptional patterns associated with the PC grade in a MENA cohort using a pathology-guided framework. The findings highlight candidate genes associated with tumor presence and grade progression and provide a foundation for further investigation in larger, well-annotated cohorts, particularly in populations that remain underrepresented in transcriptomic studies.