Fast detection of low-concentration exosomes in body fluids is of great significance in understanding the pathogenesis and disease diagnosis but is quite a challenging work due to the complex matrix, tedious pretreatment, and relatively poor sensitivity without the aid of instruments. In this work, by simply using a filter membrane to enrich the exosomes at low concentrations and the use of CuS nanoparticles as labels, we were able to detect exosomes at concentrations as low as 2 × 10 3 particles/μL in a complex matrix by the naked eye. Due to its high sensitivity, specificity, and simplicity, it can be used for the diagnosis of direct prostate cancer via a 5 mL urine sample within 2 h without the use of any instrument. This method can also be applicable for the detection of other biological nanoparticles, such as viruses, at low concentrations in a complex matrix, offering a promising candidate for point-of-care disease diagnosis with low cost.
Background: Bladder cancer (BC) is known as the eleventh most common malignant tumor all over the world, for either males or females. Developing effective regimens targeting more promising biomarkers aiming for better prognosis are required. Immune checkpoint inhibitors (ICI) have been demonstrated as a prospective and practical means to resist cancers. Theoretically, adequate infiltration of immune cells indicates more immunotherapy targets and may promise better prognosis.Methods: Full transcriptome data (n=433), clinical information (n=581) and mutation sequencing (n=412) were obtained freely from The Cancer Genome Atlas and independent mutation sequencing data of 101 samples were acquired from International Cancer Genome Consortium. Statistical processing was conducted using R packages with R x64 4.0.2. Gene biologically functional research was performed with gene set enrichment analysis (GSEA) based on Kyoto Encyclopedia of Genes and Genomes (KEGG) database. 22 types of immune cell infiltration were assessed and calculated in 398 samples of BC tumors.Results: Tumor mutation burdens (TMB) of mutant type groups were higher than wild type groups for 19 genes, except for FGFR3 and CREBBP verifying that genomic mutation associates positively with TMB in BC tumor. Kaplan-Meier analysis showed high mutation frequency on RB1 had a negative effect on prognosis of BC patients and RB1 was an independent prognostic factor (p=0.004, HR=1.776) in BC. It was also demonstrated that RB1 mainly participate in singling pathways of cell proliferation and cell cycle. Proportions and correlation of 22 types of immune cells in 433 samples were determined. Immune cells with similar function are inclined to co-exist in tumor microenvironment of BC. Among them, regulatory T cells (Tregs) were detected as a negatively correlated type immune cell to mutation of RB1 that probably increases the incidence of tumor immune escaping in BC.Conclusion: RB1 can be identified as an independent prognostic predictor, and there is a chance for contribution to poor overall survival as the mutation occurs. What's more, mutation of RB1 also functions as a biomarker that represses the infiltration of Tregs, increasing the incidence of tumor immune escaping in BC.
PurposeClear cell renal cell carcinoma (ccRCC) is one of the most common malignancies of the urinary system. This study was conducted to discover a new target that can predict the prognosis and promote the treatment of ccRCC.MethodsThe raw data were downloaded from the TCGA database, and the predictive value of ASNS for various clinicopathological features was verified in the following analysis. Then, we analyzed the potential involvement of ASNS in tumor immunity and obtained the possible pathways involving ASNS through GO/KEGG enrichment analysis and GSEA. We also further verified our findings in pathological specimens of ccRCC patients.ResultsASNS expression was significantly increased in ccRCC, which was associated with advanced clinicopathological characteristics. It was an independent prognostic factor for overall survival in 535 patients with ccRCC. Immune cell infiltration analysis revealed that ASNS expression was related to T lymphocyte infiltration of tumors and poor prognosis. Moreover, we performed relevant functional enrichment analyses of ASNS.ConclusionsASNS might play a significant role in the development and immune cell infiltration of ccRCC and serve as a valuable clinical prognostic biomarker.
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