Background: Lymphovascular invasion (LVI) is a prognostic factor in early-stage invasive breast cancer (BC). Through bioinformatics, data analyses of multiple BC cohorts revealed the positive association between interferon-stimulated gene 15 (ISG15) LVI status. Thus, we explored the prognostic significance of ISG15 in BC. Methods: The prognostic significance of ISG15 mRNA was assessed in METABRIC (n = 1980), TCGA (n = 854) and Kaplan–Meier Plotter (n = 3951). ISG15 protein was evaluated using immunohistochemistry (n = 859) in early-stage invasive BC patients with long-term follow-up. The associations between ISG15 expression and clinicopathological features, expression of immune cell markers and patient outcome data were evaluated. Results: High mRNA and protein ISG15 expression were associated with LVI, higher histological grade, larger tumour size, hormonal receptor negativity, HER2 positivity, p53 and Ki67. High ISG15 protein expression was associated with HER2-enriched BC subtypes and immune markers (CD8, FOXP3 and CD68). High ISG15 mRNA and ISG15 expressions were associated with poor patient outcome. Cox proportional multivariate analysis revealed that the elevated ISG15 expression was an independent prognostic factor of shorter BC-specific survival. Conclusion: This study provides evidence for the role of ISG15 in LVI development and BC prognosis. Further functional studies in BC are warranted to evaluate the therapeutic potential of ISG15.

Background: The Ubiquitin-conjugating enzyme 2C (UBE2C) is essential for the ubiquitin–proteasome system and is involved in cancer cell migration and apoptosis. This study aimed to determine the prognostic value of UBE2C in invasive breast cancer (BC). Methods: UBE2C was evaluated using the Molecular Taxonomy of Breast Cancer International Consortium (n = 1980), The Cancer Genome Atlas (n = 854) and Kaplan–Meier Plotter (n = 3951) cohorts. UBE2C protein expression was assessed using immunohistochemistry in the BC cohort (n = 619). The correlation between UBE2C, clinicopathological parameters and patient outcome was assessed. Results: High UBE2C mRNA and protein expressions were correlated with features of poor prognosis, including high tumour grade, large size, the presence of lymphovascular invasion, hormone receptor negativity and HER2 positivity. High UBE2C mRNA expression showed a negative association with E-cadherin, and a positive association with adhesion molecule N-cadherin, matrix metalloproteinases and cyclin-related genes. There was a positive correlation between high UBE2C protein expression and cell cycle-associated biomarkers, p53, Ki67, EGFR and PI3K. High UBE2C protein expression was an independent predictor of poor outcome (p = 0.011, HR = 1.45, 95% CI; 1.10–1.93). Conclusion: This study indicates that UBE2C is an independent prognostic biomarker in BC. These results warrant further functional validation for UBE2C as a potential therapeutic target in BC.

Non-small cell lung carcinoma (NSCLC) is a prominent type, with an 85–90% incidence in all lung cancer cases. The evidence for a particular therapy strategy for people with NSCLC is still inadequate. This review evaluates NSCLC therapies that have passed phase IV trials, emphasizing their efficiency and adverse effects. Crucial therapeutic approaches, including dacomitinib, lorlatinib, durvalumab, osimertinib, and rivaroxban, are discussed, highlighting their mechanisms of action, uses, and adverse effects. Immune checkpoint medications are recommended because of their specific activity and minimal adverse reactions. The review also investigates cooperation therapies, such as targeting immune checkpoint inhibitors and hemostasis, alongside chemotherapy, as they offer potential for future therapies. However, further research is needed to improve the safety and efficacy of current treatments, and to explore novel ways to achieve better long-term outcomes.

Background: N6-methyladenosine (m⁶A) is the most common internal RNA modification and is involved in regulation of RNA and protein expression. AlkB family member 5 (ALKBH5) is a m⁶A demethylase. Given the important role of m⁶A in biological mechanisms, m⁶A and its regulators, have been implicated in many disease processes, including cancer. However, the contribution of ALKBH5 to invasive breast cancer (BC) remains poorly understood. The aim of this study was to evaluate the clinicopathological value of ALKBH5 in BC. Methods: Publicly available data were used to investigate ALKBH5 mRNA alterations, prognostic significance, and association with clinical parameters at the genomic and transcriptomic level. Differentially expressed genes (DEGs) and enriched pathways with low or high ALKBH5 expression were investigated. Immunohistochemistry (IHC) was used to assess ALKBH5 protein expression in a large well-characterised BC series (n = 1327) to determine the clinical significance and association of ALKBH5 expression. Results: Reduced ALKBH5 mRNA expression was significantly associated with poor prognosis and unfavourable clinical parameters. ALKBH5 gene harboured few mutations and/or copy number alternations, but low ALKBH5 mRNA expression was seen. Patients with low ALKBH5 mRNA expression had a number of differentially expressed genes and enriched pathways, including the cytokine-cytokine receptor interaction pathway. Low ALKBH5 protein expression was significantly associated with unfavourable clinical parameters associated with tumour progression including larger tumour size and worse Nottingham Prognostic Index group. Conclusion: This study implicates ALKBH5 in BC and highlights the need for further functional studies to decipher the role of ALKBH5 and RNA m⁶A methylation in BC progression.

Background: Cell Division Cycle Associated 5 (CDCA5) plays a role in the phosphoinositide 3-kinase (PI3K)/AKT/mTOR signalling pathway involving cell division, cancer cell migration and apoptosis. This study aims to assess the prognostic and biological value of CDCA5 in breast cancer (BC). Methods: The biological and prognostic value of CDCA5 were evaluated at mRNA (n = 5109) and protein levels (n = 614) utilizing multiple well-characterized early stage BC cohorts. The effects of CDCA5 knockdown (KD) on multiple oncogenic assays were assessed in vitro using a panel of BC cell lines. Results: this study examined cohorts showed that high CDCA5 expression was correlated with features characteristic of aggressive behavior and poor prognosis, including the presence of high grade, large tumor size, lymphovascular invasion (LVI), hormone receptor negativity and HER2 positivity. High CDCA5 expression, at both mRNA and protein levels, was associated with shorter BC-specific survival independent of other variables (p = 0.034, Hazard ratio (HR) = 1.6, 95% CI; 1.1–2.3). In line with the clinical data, in vitro models indicated that CDCA5 depletion results in a marked decrease in BC cell invasion and migration abilities and a significant accumulation of the BC cells in the G2/M-phase. Conclusions: These results provide evidence that CDCA5 plays an important role in BC development and metastasis and could be used as a potential biomarker to predict disease progression in BC.

Background: Ventriculoperitoneal shunting (VPS) is the primary treatment for hydrocephalus, significantly improving patients’ outcomes. However, it is marred by high failure rates due to infections, which account for a third of these malfunctions and escalate morbidity, mortality, and healthcare costs. Method: This study focused on evaluating VPS infection rates, pathogens, their resistance patterns, and the impact on clinical outcomes using retrospective data from multiple hospitals in Saudi Arabia. It included data from hydrocephalus patients who underwent VPS and only considered positive cultures that were confirmed from CSF or shunt tip samples. Results: This study excluded patients with prior infections before VPS placement or those treated with alternatives to VPS. Out of 317 patients who met the inclusion criteria, the analysis revealed that 23 patients (7.26%) suffered from VPS infections, mostly within the first two weeks post-surgery (58.06% of cases), with a significant discrepancy in infection rates between hospitals. Infections predominantly involved Gram-positive bacteria (58.08%), especially coagulase-negative staphylococci and Staphylococcus aureus (25.81% and 12.90%, respectively). There was also a substantial presence of Gram-negative bacteria and fungi, accounting for 35.46% and 6.46%, respectively. Despite general antibiotic susceptibility, resistance was significant in certain cases, including multidrug-resistant isolates like Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter ursingii. Importantly, patients with VPS infections had a tenfold increase in the length of hospital stay (70.84 days, SD ± 139.5) compared to non-infected patients (7.69 days, SD ± 20.72), indicating high morbidity and associated treatment costs. Conclusions: Our results emphasize the importance of better VPS infection control and standardized hospital protocols to decrease the incidence of VPS-related infections, both in Saudi Arabia and globally.