COL8A1 is a potential prognostic biomarker associated with migration, proliferation, and tumor microenvironment in glioma.

Glioblastoma (GBM) is a common primary central nervous system tumor. The molecular mechanisms of glioma are unknown, and the prognosis is poor. Therefore, exploring the underlying mechanisms and screening for new prognostic markers and therapeutic targets is crucial. We utilized the weighted gene co-expression network analysis (WGCNA), Differentially Expressed Genes (DEGs), and LASSO-COX analysis to identify three target genes. Next, we constructed and evaluated a prognostic model, screening out COL8A1 as a risk gene. Through a sequence of cellular functional experiments, in vivo studies, and RNA sequencing, we delved into exploring the functional effects and molecular mechanisms of COL8A1 on GBM cells. Finally, the correlation between COL8A1 and tumor immune cells and different inflammatory responses was analyzed. Immunohistochemistry experiments revealed the influence of COL8A1 on macrophage polarization. The COL8A1 expression level was associated with the grade, prognosis, and tumor microenvironment (TME) of glioma. Functional experiments showed that COL8A1 inhibited GBM cell apoptosis and promoted migration, invasion, and proliferation in vitro and in vivo. We also found that COL8A1 promotes the epithelial-mesenchymal transition process and may mediate the activation of the ERK pathway through SHC1. In addition, immune infiltration analysis showed that COL8A1 was closely associated with macrophages in glioma tissues, significantly suppressing the signaling of M1-like -type macrophages and enhancing the signaling of M2-like -type macrophages. COL8A1 was first found to be associated with prognosis, progression, and immune microenvironment of glioma and may serve as a new marker of prognosis and a therapeutic target.

ADAMTSL2 is a potential prognostic biomarker and immunotherapeutic target for colorectal cancer: Bioinformatic analysis and experimental verification.

The ADAMTS Like 2 (ADAMTSL2) mutation has been identified to be associated with different human genetic diseases. The role of ADAMTSL2 is unclear in colorectal cancer (CRC). The study investigated the expression of ADAMTSL2 in both pan cancer and CRC, using data from The Cancer Genome Atlas (TCGA) database to assess its diagnostic value. The study examined the correlation between ADAMTSL2 expression levels and clinical characteristics, as well as prognosis in CRC. The study explored potential regulatory networks involving ADAMTSL2, including its association with immune infiltration, immune checkpoint genes, tumor mutational burden (TMB) / microsatellite instability (MSI), tumor stemness index (mRNAsi), and drug sensitivity in CRC. ADAMTSL2 expression was validated using GSE71187 and quantitative real-time PCR (qRT-PCR). ADAMTSL2 was aberrantly expressed in pan cancer and CRC. An increased level of ADAMTSL2 expression in patients with CRC was significantly associated with the pathologic N stage (p < 0.001), pathologic stage (p < 0.001), age (p < 0.001), histological type (p < 0.001), and neoplasm type (p = 0.001). The high expression of ADAMTSL2 in patients with CRC was found to be significantly associated with a poorer overall survival (OS) (HR: 1.67; 95% CI: 1.18-2.38; p = 0.004), progression-free survival (PFS) (HR: 1.55; 95% CI: 1.14-2.11; p = 0.005) and disease-specific survival (DSS) (HR: 1.83; 95% CI: 1.16-2.89; p = 0.010). The expression of ADAMTSL2 in patients with CRC (p = 0.009) was identified as an independent prognostic determinant. ADAMTSL2 was associated with extracellular matrix receptor (ECM-receptor) interaction, transforming growth factor ß (TGF-ß) signaling pathway, and more. ADAMTSL2 expression was correlated with immune infiltration, immune checkpoint genes, TMB / MSI and mRNAsi in CRC. ADAMTSL2 expression was significantly and negatively correlated with 1-BET-762, Trametinib, and WZ3105 in CRC. ADAMTSL2 was significantly upregulated in CRC cell lines. The high expression of ADAMTSL2 is significantly correlated with lower OS and immune infiltration of CRC. ADAMTSL2 may be a potential prognostic biomarker and immunotherapeutic target for CRC patients.

Preoperative C-reactive protein to prealbumin ratio is independently associated with prognosis in patients with resectable colorectal cancer.

BACKGROUND: Increasing attention has been drawn the prognostic value of inflammatory indices for colorectal cancer (CRC). However, the prognostic value of the preoperative C-reactive protein to prealbumin ratio (CPAR) in CRC remains unclear. METHODS: A retrospective study was conducted with 794 patients who had CRC and underwent radical surgical resection. The predictive performance of the inflammatory indices was analyzed and compared using the area under the time-dependent receiver operating characteristic curve. A competing risk regression model and Cox proportional hazard model were used to analyze the effects of CPAR on disease-free survival (DFS) and overall survival (OS), respectively. RESULTS: Patients with high CPAR (>7.25) had poor survival outcome. The CPAR had the best predictive performance among all inflammatory indices, and was significantly associated with several characteristics of tumor invasion, including histological grade, tumor stage, and tumor size. Multivariate analysis showed that high CPAR was independently associated with poor DFS (subdistribution hazard ratio = 2.28, 95% confidence interval [CI]: 1.74-2.82) and OS (hazard ratio = 1.78, 95% CI: 1.60-1.96). CONCLUSION: Preoperative CPAR assessment could serve as an effective and reliable tool for prognostic prediction in patients with resectable CRC.

Fabrication and characterization of oil-in-water pickering emulsions stabilized by ZEIN-HTCC nanoparticles as a composite layer.

In this work, the ZEIN-HTCC nanoparticles formed by zein and N-(2-hydroxy)propyl-3-trimethylammonium chitosan chloride (HTCC) were used as stabilizers to prepare oil-in-water (O/W) Pickering emulsions. The preparation conditions including shearing time, volume fraction of corn oil, mass ratio of ZEIN:HTCC and total concentration of ZEIN-HTCC of emulsions were optimized by measuring the droplet size, zeta potential, PDI and surface tension of emulsions. The ZEIN-HTCC emulsions are stable at the pH range of 4-9 and in the low salt ion concentrations up to 0.2 mol L-1, and can keep stable up to 21 d during low temperature storage. Fourier transform infrared spectroscopy (FTIR), the confocal laser scanning microscope (CLSM) and scanning electron microscopy (SEM) were used to analyze the interaction between emulsion components, revealing that zein and HTCC form a composite layer by flocculation to adsorb on the surface of oil droplets, thus preventing emulsion droplets from aggregation. This novel, long-term stable, surfactant-free, and edible zein-based Pickering emulsion could be used as potential carriers for lipophilic nutrients delivery.

Gene Biomarkers Derived from Clinical Data of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a common cancer of high mortality, mainly due to the difficulty in diagnosis during its clinical stage. Here we aim to find the gene biomarkers, which are of important significance for diagnosis and treatment. In this work, 3682 differentially expressed genes on HCC were firstly differentiated based on the Cancer Genome Atlas database (TCGA). Co-expression modules of these differentially expressed genes were then constructed based on the weighted correlation network algorithm. The correlation coefficient between the co-expression module and clinical data from the Broad GDAC Firehose was thereafter derived. Finally, the interactive network of genes was then constructed. Then, the hub genes were used to implement enrichment analysis and pathway analysis in the Database for Annotation, Visualization and Integrated Discovery (DAVID) database. Results revealed that the abnormally expressed genes in the module played an important role in the biological process including cell division, sister chromatid cohesion, DNA repair, and G1/S transition of mitotic cell cycle. Meanwhile, these genes also enriched in a few crucial pathways related to Cell cycle, Oocyte meiosis, and p53 signaling. Via investigating the closeness centrality of the interactive network, eight gene biomarkers including the CKAP2, TPX2, CDCA8, KIFC1, MELK, SGO1, RACGAP1, and KIAA1524 gene were discovered, whose functions had been indeed revealed to be correlated with HCC. This study, therefore, suggests that the abnormal expression of those eight genes may be taken as gene biomarkers of HCC.

Leucine-rich repeat receptor-like gene screen reveals that Nicotiana RXEG1 regulates glycoside hydrolase 12 MAMP detection.

Activation of innate immunity by membrane-localized receptors is conserved across eukaryotes. Plant genomes contain hundreds of such receptor-like genes and those encoding proteins with an extracellular leucine-rich repeat (LRR) domain represent the largest family. Here, we develop a high-throughput approach to study LRR receptor-like genes on a genome-wide scale. In total, 257 tobacco rattle virus-based constructs are generated to target 386 of the 403 identified LRR receptor-like genes in Nicotiana benthamiana for silencing. Using this toolkit, we identify the LRR receptor-like protein Response to XEG1 (RXEG1) that specifically recognizes the glycoside hydrolase 12 protein XEG1. RXEG1 associates with XEG1 via the LRR domain in the apoplast and forms a complex with the LRR receptor-like kinases BAK1 and SOBIR1 to transduce the XEG1-induced defense signal. Thus, this genome-wide silencing assay is demonstrated to be an efficient toolkit to pinpoint new immune receptors, which will contribute to developing durable disease resistance.