Renal clear cell carcinoma (ccRCC) is the world's most common form of cancer. Up to a third will develop metastases; the 5-year survival rate of the patients was only 14%. Practical prognostic markers remain to be discovered. Kinesin-like protein (KIFC1), a critical factor in maintaining the stability of the microtubule system, has significant prognostic value in some tumors. We analyzed the prognostic value, associated signaling pathways, and regulatory mechanisms of KIFC1 in ccRCC through bioinformatics and proteomics. Concretely, both mRNA and protein expression levels of KIFC1 were dramatically upregulated. KIFC1 is an independent prognostic factor for ccRCC. The expression of KIFC1 showed a significant positive correlation (Spearman coefficient > 0.7) with tumor proliferation-related pathways (tumor proliferation, G2/M checkpoint, and DNA replication) and tumor inflammation. Further, intratumoral immune cell analysis revealed that high expression of KIFC1 predicted more infiltration of CD8 + T and CD4 + T cells (p < 0.001). However, there was a significant positive relationship between CD8 + T cells and numerous immune checkpoint genes. CD8 + T cells in tumors from the KIFC1 high expression group were at the dysregulated state. High expression of KIFC1 may predict a poor immunotherapy outcome. By proteomics, we analyzed proteins interacting with KIFC1; spliceosome proteins had the most significant enrichment, indicating the new directions for KIFC1 investigation. In conclusion, our study identified KIFC1 as an independent prognostic factor in renal clear cell carcinoma, and the associated processes involved tumor proliferation and immune infiltration. KIFC1 had a close relationship with spliceosome proteins; it may be a new research direction.

Low-grade glioma (LGG) is a primary, slow-growing brain tumor; however, its treatment and prognosis remain challenging. In this study, we analyzed cancer data from the TCGA database, focusing particularly on the expression of the CDKN3 gene in LGG. The results showed that high CDKN3 expression in LGG patients was significantly associated with poor survival outcomes. Further gene expression analysis revealed that 379 genes were significantly upregulated in LGG samples with high CDKN3 expression, and these genes were primarily involved in the mitotic cell cycle and extracellular matrix organization. Additionally, high CDKN3 expression was closely linked to key signaling pathways such as tumor inflammation, hypoxic response, and tumor proliferation. Immune microenvironment analysis showed that high CDKN3 expression significantly increased the expression of CD4 + T cells and specific immune checkpoint genes, suggesting a potentially poor response to immune checkpoint blockade therapy. Through in vitro and in vivo experiments, we confirmed that CDKN3 silencing significantly inhibited the proliferative capacity of LGG cells. Proteomics revealed that CDKN3 can bind ARG1 and inhibite the intracellular arginase activity. These findings not only improve our understanding of LGG biology but also provide scientific evidence for developing potential therapeutic strategies targeting CDKN3.

Due to an error during figure assembly, in Figure 8A two cells in the stage "telophase I" were selected. One exemplary cell has been replaced with a "telophase II" stage cell.

Esophageal squamous cell carcinoma (ESCC) is a highly aggressive upper gastrointestinal tumor with a 5-year survival rate of less than 20%. Therefore, developing new effective prognostic markers is of great clinical significance. In this study, we utilized datasets specific to ESCC and analyzed differentially expressed genes in each dataset. By conducting Venn analysis, we identified genes that exhibited significant differential expression across multiple datasets. Through gene interaction network analysis, we identified a core set of genes (23 genes) and established a prognostic model for ESCC using the COX algorithm (p=0.000245, 3-year AUC=0.98). The high-risk group of patients showed a significantly worse prognosis compared to the low-risk group. Furthermore, immune interaction network analysis revealed a strong association between increased risk values and an elevated presence of M2 macrophages within tumor tissues. Drug sensitivity analysis indicated that the high-risk group of patients exhibited poorer sensitivity to first-line chemotherapy drugs for ESCC. Notably, there was a significant positive correlation between the expression of core genes and immune checkpoint genes such as SIGLEC15, PDCD1LG2, and HVCR2. The high-risk group exhibits decreased Tumor Immune Dysfunction and Exclusion (TIDE) values, indicating that immune checkpoint blockade therapy might result in more favorable outcomes for these individuals. The immune checkpoint blockade (ICB) therapy may potentially yield better outcomes for these patients. In summary, through comprehensive bioinformatics analysis, we have established a highly effective prognostic model consisting of 23 genes for ESCC. An increased risk score in this model indicates a stronger infiltration of M2 macrophages and poorer sensitivity to chemotherapy drugs. Moreover, immune checkpoint blockade therapy may hold greater benefits for patients in the high-risk group.

Introduction: Wiskott–Aldrich syndrome protein family member 1 ( WASF1 ) truncating variants, such as c.1516C>T (p.Arg506Ter), are established causes of neurodevelopmental disorders (NDDs), but their underlying pathogenic mechanism remains debated. This study aimed to clarify the disease mechanism and identify potential therapeutic leads. Methods: We characterized a novel, asymptomatic WASF1 truncating variant (c.873delA) and compared its clinical and molecular consequences with those of the known pathogenic c.1516C>T variant. To target the likely pathogenic mutant protein, we performed high‑throughput virtual screening of the ZINC20 database. Results: Despite a similar reduction in wild‑type protein levels, the c.873delA variant did not cause neurological symptoms, in contrast to c.1516C>T. This observation supports a dominant‑negative, gain‑of‑function, or altered protein function mechanism rather than simple haploinsufficiency; however, the precise mechanism could not be definitively resolved from the available genetic and protein expression data. Virtual screening identified ZINC000101023849 as a high‑affinity lead compound with favorable drug‑like properties. Discussion: This study provides key evidence that WASF1 ‑related NDDs likely arise from a non‑haploinsufficiency mechanism and delivers a promising chemical lead for targeted therapy development. Further studies are needed to confirm the exact pathogenic mechanism and to validate the therapeutic potential of the identified compound.