Many studies have demonstrated that neuroinflammation contributes to the onset and development of Alzheimer’s disease (AD). The infiltration of immune cells in the brain was observed in AD. The purpose of the present study was to verify potential mechanisms and screen out biomarkers related to immune infiltration in AD. We collected the expression profiling datasets of AD patients and healthy donors from the NCBI’s Gene Expression Omnibus (GEO) database. We confirmed that immune-related mechanisms were involved in AD using differentially expressed genes analysis and functional enrichment analysis. We then found that M2 macrophage infiltration was most positively correlated with AD according to the CIBERSORT algorithm and a weighted gene co-expression network analysis (WGCNA). TLR2, FCGR2A, ITGB2, NCKAP1L and CYBA were identified as hub genes correlated with M2 macrophage infiltration in AD. Furthermore, the expression levels of these hub genes were positively correlated with Aβ42 and β-secretase activity. A diagnostic model of these hub genes was constructed, which showed a high area under the curve (AUC) value in both the derivation and validation cohorts. Overall, our work further expanded our understanding of the immunological mechanisms of AD and provided new insights into therapeutic strategies in AD.

To establish a new accumulating model to enhance the accuracy of prostate cancer (PCa) diagnosis by incorporating prostate-specific antigen (PSA) and its derivative data into the Prostate Imaging-Reporting and Data System version 2 (PI-RADS v2). A total of 357 patients who underwent prostate biopsy between January 2014 and December 2017 were included in this study. All patients had 3.0 T multiparametric magnetic resonance imaging (MRI) and complete laboratory examinations. PI-RADS v2 was used to assess the imaging. PSA, PSA density (PSAD), the free/total PSA ratio (f/t PSA) and the Gleason score (GS) were classified into four-tiered levels, and optimal weights were pursued on these managed levels to build a PCa accumulating model. A receiver operating characteristic curve was generated. In all, 174 patients (48.7%) had benign prostatic hyperplasia, and 183 (51.3%) had PCa, among whom 149 (81.4%, 149/183) had clinically significant PCa. The established model 6 (PI-RADS v2 + level of PSAD + level of f/t PSA+ level of PSA) had a sensitivity and specificity of 81.4 and 84.5%, respectively, at the cut-off point of 11 in PCa diagnosis. Correspondingly, at the 12 cut-off point, the sensitivity and specificity were 87.7 and 83.0%, respectively, in diagnosing clinically significant PCa. The score of the new accumulating system was significantly different among the defined GS groups (p < 0.001). The mean values and 95% confidence intervals for GS 1–4 groups were 10.20 (9.63–10.40), 12.03 (11.19–12.87), 14.12 (13.60–14.64) and 15.44 (15.09–15.79). A new PCa accumulating model may be useful in improving the accuracy of the primary diagnosis of PCa and helpful in the clinical decision to perform a biopsy when MRI results are negative.

Background: Previous studies have revealed the critical functions of NEK2 in controlling the cell cycle which is linked to poor prognosis in multiple tumor types, but less research has been devoted to clear cell renal cell carcinoma (ccRCC). Methods: We downloaded clinical data from the gene expression omnibus (GEO) and TCGA databases together with transcriptional and mutational datasets. Strongly coexpressed genes with NEK2 were extracted from TCGA-KIRC cohort, and were submitted to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) for functional analyses. According to NEK2 levels, the survival status, mutational characteristics, response to immunotherapy and sensitivity to drugs of the patients were studied. The potential correlations between NEK2 levels and immune cell state as well as immune cell infiltration were examined using the GEPIA, TIMER and TISIDB databases. Double immunofluorescence (IF) was performed to identify the NEK2 overexpression and relationship with CD8 in ccRCC. Results: The NEK2 gene was overexpressed and would enhance the nuclear division and cell cycle activities in ccRCC. ccRCC patients with high NEK2 expression had worse clinical outcomes, higher mutation burden and better therapeutic response. Moreover, NEK2 gene overexpression was positively related to various immune cell marker sets, which was also proved by validation cohort, and more infiltration of various immune cells. Conclusion: ccRCC patients with NEK2 high expression have a poorer prognosis than those with NEK2 low expression, resulting from its function of promoting proliferation, accompanied by increased infiltration of CD8 + T cells and Tregs and T-cell exhaustion and will respond better to proper treatments.

Background: Personalized anti-tumor therapy that activates the immune response has demonstrated clinical benefits in various cancers. However, its efficacy against testicular cancer (TC) remains uncertain. This study aims to identify suitable patients for anti-tumor immunotherapy and to uncover potential therapeutic targets in TC for the development of tailored anti-tumor immunotherapy. Methods: Consensus clustering analysis was conducted to delineate immune subtypes, while weighted gene co-expression network analysis (WGCNA), least absolute shrinkage and selection operator (LASSO) regression, and support vector machine (SVM) algorithms were employed to evaluate the potential efficacy of anti-tumor immunotherapy. Candidate immunotherapy targets were systematically identified through multi-gene panel analyses and subsequently validated using molecular biology assays. A prioritized target emerging from cellular screening was further evaluated for its capacity to potentiate anti-tumor immunity. The therapeutic efficacy of this candidate was rigorously confirmed through a comprehensive suite of immunological experiments. Results: Following systematic screening of five candidate genes (WNT11, FAM181B, GRK5, FSCN1, and ECHS1), GRK5 emerged as a promising therapeutic target for immunotherapy based on its distinct functional and molecular associations with immune evasion mechanisms. Cellular functional assays revealed that GRK5 knockdown significantly attenuated the malignant phenotype of testicular cancer cells, as evidenced by reduced proliferative capacity and invasive potential. Complementary immunological validation established that specific targeting of GRK5 with the selective antagonist GRK5-IN-2 disrupts immune evasion pathways in testicular cancer, as quantified by T-cell-mediated cytotoxicity. Conclusions: These findings position GRK5 as a critical modulator of tumor-immune escape, warranting further preclinical exploration of GRK5-IN-2 as a candidate immunotherapeutic agent.