PurposePersistent toe walking in children is often considered idiopathic; however, increasing evidence suggests that alterations in the PMP22 gene—implicated in Charcot–Marie–Tooth disease type 1 A (CMT1A) and Hereditary Neuropathy with Liability to Pressure Palsies (HNPP)—may contribute to its pathogenesis. This study investigates the association between PMP22 variants (duplications, deletions, and point mutations) and toe walking in children, aiming to delineate their clinical and genetic characteristics.MethodsA retrospective analysis was performed on 22 pediatric patients (mean age: 7.7 years) with persistent toe walking and confirmed PMP22 variants identified through a 49-gene next-generation sequencing (NGS) panel. In selected cases, Multiplex Ligation-dependent Probe Amplification (MLPA) was applied to confirm copy number variations. Comprehensive clinical evaluations included musculoskeletal, neurological, and developmental assessments.ResultsAll identified variants demonstrated dominant inheritance. Pathogenic variants were present in 54.5 % of patients, likely pathogenic in 31.8 %, and variants of uncertain significance (VUS) in 13.6 %. Among pathogenic cases, most carried PMP22 duplications, one had a deletion, and the remainder harbored the missense variant p.(Thr118Met). The three VUS carriers exhibited comparatively milder phenotypes, such as muscle cramps, lumbar hyperlordosis, mild dorsiflexion restriction, hyporeflexia, pes cavus, and clinodactyly/brachydactyly; only one presented with tremor. Lumbar hyperlordosis (90.9 %) and pes cavus (90.9 %) were the most consistent findings.ConclusionsPersistent toe walking may represent an early sign of PMP22-related neuropathies rather than a benign idiopathic gait pattern. The predominance of PMP22 duplications and characteristic neuromuscular features highlight the clinical utility of integrating NGS and MLPA testing for accurate diagnosis, targeted management, and genetic counseling.

BackgroundEarly-stage diagnosis, absence of specific reliable biomarkers, and better clinical management of colorectal cancer (CRC) remain major challenges. The Rspondin2 (RSPO2) gene is one of the most potent enablers of Wnt signaling, having contrasting aspects in tumor development and progression.AimWe aimed to identify the role of RSPO2 as a molecular biomarker by evaluating its methylation and expression profiles in CRC tissue samples to identify biomarker potential.MethodologyCombined bisulfite restriction analysis (CoBRA) and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to access the change in methylation pattern and expression profile of RSPO2 in 52 CRC tissue samples. DNA methylome and transcriptome profiling of CRC samples were hierarchically clustered, and prognostic utility was measured using a Kaplan-Meier (K-M) plot and univariate analysis.ResultsRSPO2 was hypermethylated (33/52; 63.46 %) and significantly associated with early-stage (I+II, p = 0.04) CRC tissue and exhibited low RSPO2 expression (42/52; 80.76 %). Hierarchical clustering stratified the samples into two distinct clusters that share some significant clinical and molecular factors specific for cluster 1 such as LN status (p < 0.0001) and lymphovascular invasion (p = 0.0013) while staging (p < 0.0001) and RSPO2 methylation (p = 0.0402) in cluster 2, which are valuable for personalized medicine. K-M plot analysis showed that patients with low RSPO2 expression have poor disease-free survival but could not be a risk factor.ConclusionRSPO2 may be a potential biomarker for early-stage detection and provide valuable insight into the diagnosis of patients with CRC.

Glioblastoma (GB) remains the most aggressive and treatment-resistant primary brain tumor, characterized by extensive heterogeneity, therapeutic resistance, and dismal prognosis. In this comprehensive review, we aimed to synthesize emerging insights into the roles of non-coding RNAs (ncRNAs)—including microRNAs, long non-coding RNAs, circular RNAs, and PIWI-interacting RNAs—in the regulation of glioblastoma progression, resistance mechanisms, and potential therapeutic strategies. We critically evaluated the molecular functions of ncRNAs in key oncogenic processes such as proliferation, angiogenesis, epithelial–mesenchymal transition (EMT), and immune evasion. Additionally, we reviewed current detection methods, delivery technologies, and clinical trials targeting these ncRNAs. A central goal of this review was to bridge a notable gap in the literature by highlighting underrepresented ncRNA classes such as circRNAs and piRNAs, which exhibit regulatory complexity and potential as biomarkers and therapeutic agents in GB. We further discussed delivery challenges posed by the blood–brain barrier and explored promising nanocarrier and exosome-based approaches to enhance therapeutic targeting. Through curated case studies, we showcased the translational potential of targeting specific ncRNAs to reverse multiple resistance types and improve immunotherapy response. This review provides a consolidated framework for understanding the dynamic role of ncRNAs in glioblastoma and proposes an expanded toolkit for precision oncology approaches. Our findings not only underscore the therapeutic promise of ncRNAs but also call for future investigations into the lesser-known subclasses that could redefine the landscape of GB management.

BackgroundPrevious research on connection between the ABO blood group and bladder cancer has been based on determining the ABO phenotype. This specific research is extended to the molecular level, providing more information about particular ABO alleles. AimTo investigate the impact of the ABO blood group genotype or phenotype as a risk factor for urinary bladder cancer. Material and MethodsIn the case-control study, we included 74 patients who underwent surgery for a urinary bladder tumor at the Urology Clinic, Clinical Hospital Centre Zagreb, in 2021 and 2022. The control group comprised 142 asymptomatic and healthy blood donors. ABO genotyping to five basic alleles was done using a polymerase chain reaction with sequence specific primers (PCR-SSP). We compared ABO phenotypes, genotypes and alleles between patients and the healthy controls, and investigated their distribution according to the clinical and histological stage and recurrence rate. ResultsNo statistically significant difference was found among the groups, nor for the observed disease stages in terms of the phenotype and genotype. At the allele level, the results show a significantly lower proportion of malignancy in O1 (P<0.001), A1 (P<0.001) and B (P=0.013), and a lower proportion of metastatic disease in A2 (0%, P=0.024). We also found significantly higher proportions of high-grade tumors in patients with O1 (71.4%, P<0.001), A1 (70.1%, P=0.019), of non-muscle invasive tumors in patients with O1 (55.1%, P<0.001), O2 (100%, P=0.045), and recurrent tumors in patients with O1 (70.2%, P<0.001) and A1 (74.2%, P=0.007) alleles. ConclusionWe did not find an association between the ABO blood group genotype or phenotype as a genetic risk factor for urinary bladder cancer. However, an analysis at the allelic level revealed a statistically significant association between certain alleles of the ABO blood group system and urinary bladder tumors, clinical or histological stage and recurrence rate, respectively.

Background The widespread implementation of computed tomography has significantly increased the detection of small pulmonary nodules, including atypical adenomatous hyperplasia, minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IAC). Few studies have focused on the genomic differences between MIA and IAC. Methods We retrospectively analyzed patients with lung adenocarcinoma (LUAD) who underwent surgery from January 2020 to December 2023. Patients were categorized into MIA and IAC groups. The mutation status of common driver genes was assessed using next-generation sequencing. Results A total of 422 LUAD patients were included in the study, comprising 119 MIA cases and 303 IAC cases. MIA patients were younger and predominantly female compared with IAC patients. EGFR mutations were detected in 251 patients (59.5%), with the frequency of EGFR mutations increasing from 37.0% in MIA to 68.3% in IAC ( p < 0.001). TP53 mutations were found in 108 patients (25.6%), with 7 patients (5.9%) in MIA and 101 patients (33.3%) in IAC ( p < 0.001). ERBB2 mutations were identified in 23 MIA patients (19.3%) and 20 IAC patients (6.6%) ( p < 0.001). Additionally, CDKN2A mutations were detected in 23 IAC patients (7.6%), while no mutations in this gene were found in the MIA group. Moreover, ALK and RET gene fusions were identified in 11 patients, respectively. Conclusion ERBB2 mutations and RET fusions are early genomic events in LUAD, while TP53 and CDKN2A mutations and ALK fusions occur later. Genomic intratumor heterogeneity likely arises early, before invasive characteristics develop.