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Backgrounds. Glioma stands as one of the most formidable brain tumor types, with patient outcomes remaining bleak even in the face of advancements in treatment modalities. FBXW4, a constituent of the F‐box and WD repeat domain‐containing protein family, is recognized for its participation in diverse cellular activities, including those related to tumor dynamics. Yet, the therapeutic relevance and specific role of FBXW4 in the context of glioma are not well defined. This study aims to elucidate the functional dynamics and significance of FBXW4 in glioma cases. Methods. This research undertook a comprehensive analysis of FBXW4's expression patterns and clinical relevance in glioma by harnessing data from the TCGA and GTEx databases. Results. The investigation revealed a distinct downregulation of FBXW4 in glioma tissues compared to normal brain counterparts, with a pronounced correlation between FBXW4 levels and disease severity. Intriguingly, FBXW4 expression inversely related to WHO tumor grades, with the most advanced grade IV gliomas exhibiting the lowest FBXW4 levels, whereas grade II tumors demonstrated the highest. Cases presenting with IDH1/2 mutations or 1p/19q codeletions were also associated with elevated FBXW4 levels. Furthermore, diminished FBXW4 expression aligned with an increased risk of mortality. Conclusions. The findings suggest that FBXW4 holds promise as a prognostic marker and a potential therapeutic avenue in glioma management. Nonetheless, future research is imperative to decode the intricate signaling pathways involving FBXW4 and to understand its broader clinical ramifications in glioma treatment paradigms. [ABSTRACT FROM AUTHOR]

Backgroundsand Aims. Colorectal cancer (CRC) represents a major global health challenge, necessitating comprehensive investigations into its underlying molecular mechanisms to enhance diagnostic and therapeutic strategies. This study focuses on elucidating the oncogenic role of Membrane‐Associated Ring‐CH‐Type Finger 9 (MARCHF9), a RING‐Type E3 ubiquitin transferase, in CRC. We aim to assess MARCHF9's clinical significance, functional impact on CRC progression, and its potential as a prognostic biomarker. Methods. We leveraged data from the Cancer Genome Atlas (TCGA) cohort to evaluate MARCHF9 expression profiles in CRC. In vitro experiments involved siRNA‐mediated MARCHF9 knockdown in COAD cell lines (SW480 and LoVo). Cell proliferation and invasion assays were conducted to investigate MARCHF9's functional relevance. Survival analyses were performed to assess its prognostic role. Results. Our analysis revealed significantly elevated MARCHF9 expression in CRC tissues compared to normal colorectal tissues (P < 0.05). High MARCHF9 expression correlated with advanced clinical stages, distant metastases, and the presence of residual tumors in CRC patients. Survival analyses demonstrated that high MARCHF9 expression predicted unfavorable overall and disease‐free survival outcomes (P < 0.05). In vitro experiments further supported its oncogenic potential, with MARCHF9 knockdown inhibiting COAD cell proliferation and invasion. Conclusions. This study unveils the oncogenic role of MARCHF9 in CRC, highlighting its clinical relevance as a potential biomarker and therapeutic target. MARCHF9's association with adverse clinicopathological features and its functional impact on cancer cell behavior underscore its significance in CRC progression. Further research is essential to elucidate precise mechanisms by which MARCHF9 enhances tumorigenesis and to explore its therapeutic potential in CRC management. [ABSTRACT FROM AUTHOR]

Esophageal cancer is a major global health challenge with a poor prognosis. Recent studies underscore the extracellular matrix (ECM) role in cancer progression, but the full impact of ECM‐related genes on patient outcomes remains unclear. Our study utilized next‐generation sequencing and clinical data from esophageal cancer patients provided by The Cancer Genome Atlas, employing the R package in RStudio for computational analysis. This analysis identified significant associations between patient survival and various ECM‐related genes, including IBSP, LINGO4, COL26A1, MMP12, KLK4, RTBDN, TENM1, GDF15, and RUNX1. Consequently, we developed a prognostic model to predict patient outcomes, which demonstrated clear survival differences between high‐risk and low‐risk patient groups. Our comprehensive review encompassed clinical correlations, biological pathways, and variations in immune response among these risk categories. We also constructed a nomogram integrating clinical information with risk assessment. Focusing on the TENM1 gene, we found it significantly impacts immune response, showing a positive correlation with T helper cells, NK cells, and CD8+ T cells, but a negative correlation with neutrophils and Th17 cells. Gene Set Enrichment Analysis revealed enhanced pathways related to pancreatic beta cells, spermatogenesis, apical junctions, and muscle formation in patients with high TENM1 expression. This research provides new insights into the role of ECM genes in esophageal cancer and informs future research directions. [ABSTRACT FROM AUTHOR]

Backgrounds. Solute carrier 39A1 (SLC39A1) is an indirect zinc transporter which showed diverse tumor-related functions in different malignancies. Here, we aimed to investigate its expression and role in gastric adenocarcinoma. Methods. A retrospective gastric adenocarcinoma cohort (n  = 154) was collected from our hospital to test their tissue expression of SLC39A1 through immunohistochemical staining method. After SLC39A1 overexpression or knockdown, proliferation and invasion assays were conducted for proliferation and invasion estimation, respectively. Xenograft in nude mice was used as the in vivo strategy to validate in vitro findings. Results. Compared with adjacent stomach tissues, gastric adenocarcinoma tissues showed significantly higher SLC39A1 on both mRNA and protein levels. Higher SLC39A1 was observed in patients with larger tumor size (P = 0.003) and advanced tumor stages (P < 0.001). Univariate (P = 0.001) and multivariate analyses (P = 0.035) confirmed the independent prognostic significance of SLC39A1 on gastric adenocarcinoma outcomes. The median survival time was 22.0 months in patients with high-SLC39A1 expression, while up to 57.0 months in those with low-SLC39A1 (P = 0.001). In vitro and in vivo assays demonstrated that overexpressing SLC39A1 could promote gastric cancer growth and invasion, while silencing SLC39A1 led to opposite effects. Conclusions. Aberrant high-SLC39A1 expression can serve as an independent unfavorable prognostic factor for gastric adenocarcinoma. High SLC39A1 is critical for a more aggressive tumor phenotype by promoting cell proliferation and invasion. Therefore, targeting SLC39A1 may provide novel therapeutic insights. [ABSTRACT FROM AUTHOR]

Colon cancer is the most common malignant tumor of the gastrointestinal tract, and approximately 80%–90% of colon cancers are colon adenocarcinomas (COADs). This study aimed to screen key microRNAs (miRNAs) associated with COAD. Differentially expressed (DE) miRNAs were screened between COAD and adjacent cancer samples based on the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas obtained from datasets. The miRNAs of interest were validated using quantitative real-time polymerase chain reaction. Moreover, the effects of hsa-miR-135b-5p on the biological behavior of COAD cells were observed. To obtain the target genes of hsa-miR-135b-5p, transcriptome sequencing of the SW480 cells was performed, followed by protein-protein interaction (PPI) network and hsa-miR-135b-5p-target gene regulatory network construction and prognostic analysis. Downregulation of hsa-miR-135b-5p significantly inhibited SW480 cell proliferation, migration, and invasion and significantly facilitated apoptosis (P  < 0.05). A total of 3384 DEmRNAs were screened, and enrichment analysis showed that the upregulated mRNAs were enriched in 25 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and 326 Gene Ontology Biological Processes (GO-BPs) while the downregulated mRNAs were enriched in 20 KEGG pathways and 276 GO-BPs. A PPI network was then constructed, and H2BC14, H2BC3, and H4C11 had a higher degree. In addition, a total of 352 hsa-miR-135b-5p-gene regulatory relationships were identified. Prognostic analysis showed that FOXN2 , NSA2 , MYCBP , DIRAS2 , DESI1 , and RAB33B had prognostic significance (P  < 0.05). In addition, the validation analysis results showed that FOXN2 , NSA2 , and DESI1 were significantly expressed between the miR-135b-5p-inhibitor and negative control groups (P  < 0.05). Therefore, downregulation of hsa-miR-135b-5p inhibits cell proliferation, migration, and invasion in COAD, and carcinogenesis may function by targeting FOXN2 , NSA2 , MYCBP , DIRAS2 , DESI1 , and RAB33B. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is a manifestation of hepatic metabolic syndrome that varies in severity. Hepatocellular carcinoma progresses from NAFLD when there is heterogeneity in the infiltration of immune cells and molecules. A precise molecular classification of NAFLD remains lacking, allowing further exploration of the link between NAFLD and hepatocellular carcinoma. In this work, a weighted gene coexpression network analysis was used to identify two coexpression modules based on multiple omics data used to differentiate NAFLD subtypes. Additionally, key genes in the process of glucose metabolism and NAFLD were used to construct a prognostic model in a cohort of patients with hepatocellular carcinoma. Furthermore, the specific expression of signature genes in hepatocellular carcinoma cells was analyzed using a single-cell RNA sequencing approach. A total of 19 liver tissues of NAFLD patients were obtained from the GEO database, and 81 glucose metabolism-related genes were downloaded from the CTD database. In addition, based on nine signature genes, we constructed a prognostic model to divide the HCC cohort into high and low-risk groups. We also demonstrated a significant correlation between prognostic models and clinical phenotypes. Furthermore, we integrated single-cell RNA-sequencing data and immunology data to assess potential relationships between different molecular subtypes and hepatocellular carcinoma. Finally, our study discovered that the glucose metabolism pathway may play an important role in the process of NAFLD-hepatocellular carcinoma. In addition, three glucose metabolism-related genes (SERPINE1, VCAN, and TFPI2) may be the potential targets for the immunotherapy of patients with NAFLD-hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]