PA28γ was suggested to play a role in malignant progression. This paper aimed to investigate the association between PA28γ and the prognosis of oral squamous cell carcinoma (OSCC) in cohort studies.
...The PA28γ expression level was assessed by immunohistochemistry in a total of 368 OSCC patients from three independent cohorts. The Cox proportional hazards regression model was used to determine multivariate hazard ratios for Overall Survival (OS). Model discrimination was measured using C Statistic. Additionally, OS was analyzed in Head Neck Squamous Cell Carcinoma (HNSCC) patients from The Cancer Genome Atlas (TCGA) data set. Functional analyses were conducted both in-vitro and in-vivo.
The median follow-up times of patients in the three studies were 60, 52, and 51months. High expression of PA28γ was identified in tumors from 179 of 368 patients (48.6%). Compared with low expression, high expression of PA28γ was strongly associated with worse OS, with relative risks of 5.14 (95% CI, 2.51–10.5; P<0.001), 2.82 (95% CI, 1.73–4.61; P<0.001), and 3.85 (95% CI, 1.59–9.37; P=0.003). PA28γ expression was also associated with disease-free survival in all three cohorts (P<0.005). These findings are consistent with TCGA HNSCC data (P<0.006). The prediction of all-cause mortality was significantly improved when PA28γ was added to the traditional clinical factors (Model 3, C statistic value: 0.78 VS 0.73, P=0.016). In functional analyses, we found that PA28γ silencing dramatically inhibited the growth, proliferation and mobility of OSCC cells in vitro and reduced tumor growth and angiogenesis in tumor-bearing mice.
PA28γ overexpression is associated with adverse prognosis in patients with OSCC. The aberrant expression of PA28γ may contribute to the pathogenesis and progression of OSCC.
OSCC is one of the most common HNSCC, which have a high lethally rate. However, few prognostic markers have been applied in the clinical practice. We found that PA28γ in OSCC tumor tissues were significantly high expression than those in normal tissues. As the results of the three cohorts from two independent research centers and from an additional validation cohort from a US population in the TCGA dataset, we demonstrate PA28γ is a good predictor of the risk of death in OSCC. Meanwhile, we demonstrate PA28γ have a potential role in OSCC tumorigenesis.
•PA28γ protein over-expressed in a large subset of patients with OSCC•PA28γ was a prognostic factor in OSCC based on the results of three cohorts in China•The analysis of PA28γ mRNA abundance in a US/non-Chinese cohort from TCGA dataset consistent with Chinese-cohort study•PA28γ silencing could affect the tumor biological behavior of OSCC both in vitro and vivo.
Integrins, which act as an important role in the connection between cells and extra-cellular environments, are important cell surface receptors. Integrins have been demonstrated to play critical ...roles in many aspects of the progression of oral squamous cell carcinoma (OSCC). The aim of this study was to investigate the association between single nucleotide polymorphisms (SNPs) in microRNA-binding sites of integrin genes and the susceptibility and progression of OSCC in Chinese Han Population. We recruited 167 OSCC patients and 200 cancer-free controls from three independent medical centers. Genotyping was completed successfully for the five selected integrin SNPs: rs1062484 (integrin α3), rs11902171 (integrin αv), rs17468 (integrin β1), rs3809865 (integrin β3), and rs2675 (integrin β5). The results demonstrated that the A allele of rs3809865 T/A (a T-to-A nucleotide change), a functional polymorphism in the 3′UTR of integrin β3 gene, was associated with OSCC risk (p < 0.05). In addition, the association analysis between this SNP and integrin β3 mRNA expression level in the patients’ peripheral blood mononuclear cells indicated that OSCC patients carrying the A allele would have a lower integrin β3 expression level (p = 0.047). Meanwhile, survival analysis showed that the C allele of rs2675 A/C (nucleotide change from A to C), another 3′UTR polymorphism in integrin β5 gene, was related with progression of OSCC. Overall, our results suggest that rs3809865 and rs2675 may contribute to OSCC risk and progression in Chinese Han Population. These two SNPs may be used as potential diagnostic and prognostic biomarkers for OSCC in future.
Understanding the interactions between tumor and the host immune system is critical to finding prognostic biomarkers, reducing drug resistance, and developing new therapies. Novel computational ...methods are needed to estimate tumor-infiltrating immune cells and understand tumor-immune interactions in cancers.
We analyze tumor-infiltrating immune cells in over 10,000 RNA-seq samples across 23 cancer types from The Cancer Genome Atlas (TCGA). Our computationally inferred immune infiltrates associate much more strongly with patient clinical features, viral infection status, and cancer genetic alterations than other computational approaches. Analysis of cancer/testis antigen expression and CD8 T-cell abundance suggests that MAGEA3 is a potential immune target in melanoma, but not in non-small cell lung cancer, and implicates SPAG5 as an alternative cancer vaccine target in multiple cancers. We find that melanomas expressing high levels of CTLA4 separate into two distinct groups with respect to CD8 T-cell infiltration, which might influence clinical responses to anti-CTLA4 agents. We observe similar dichotomy of TIM3 expression with respect to CD8 T cells in kidney cancer and validate it experimentally. The abundance of immune infiltration, together with our downstream analyses and findings, are accessible through TIMER, a public resource at http://cistrome.org/TIMER .
We develop a computational approach to study tumor-infiltrating immune cells and their interactions with cancer cells. Our resource of immune-infiltrate levels, clinical associations, as well as predicted therapeutic markers may inform effective cancer vaccine and checkpoint blockade therapies.
Abstract
Single-cell CRISPR screens have been widely used to investigate gene regulatory circuits in diverse biological systems. The recent development of single-cell CRISPR screens has enabled ...multimodal profiling of perturbed cells with both gene expression, chromatin accessibility and protein levels. However, current methods cannot meet the analysis requirements of different types of data and have limited functions. Here, we introduce Single-cell CRISPR screens data analysEs and perturbation modEling (SCREE) as a comprehensive and flexible pipeline to facilitate the analyses of various types of single-cell CRISPR screens data. SCREE performs read alignment, sgRNA assignment, quality control, clustering and visualization, perturbation enrichment evaluation, perturbation efficiency modeling, gene regulatory score calculation and functional analyses of perturbations for single-cell CRISPR screens with both RNA, ATAC and multimodal readout. SCREE is available at https://github.com/wanglabtongji/SCREE.
•A novel cathode material was obtained from paper mulberry.•PMAC700-3 presents high content of self-doped tetra-heteroatoms.•Efficient 3D interconnected structure inherits from paper ...mulberry.•Significantly improved electrochemical performance of ZHSC based on PMAC700-3 cathode.•Superior areal capacitance was achieved under ultra-high mass loading.
Porous carbon has been reported as a promising cathode material for zinc-ion hybrid supercapacitors (ZHSCs). However, it is limited by inferior ionic diffusion and insufficient active adsorption sites during charge/discharge process. Herein, a tetra-heteroatom self-doped and hierarchical porous carbon material (PMAC700-3) derived from paper mulberry has been fabricated through facile carbonization and activation process. Owing to the high tetra-heteroatom content (∼15.76 % atomic ratio of N, O, S, P), hierarchical porous structure, and specific surface area (1736.1 m2 g−1), the PMAC700-3 cathode exhibits considerable ionic diffusion, abundant active adsorption sites, and superior electric conductivity, thereby significantly improving the electrochemical performance of ZHSCs. The ZHSC based on PMAC700-3 cathode delivers an excellent specific capacitance of 240.7 F g−1 at 0.5 A/g, energy density of 108.3 Wh kg−1, power density of 450 W kg−1, along with exceptional cycling stability (97.7 % capacity retention after 10,000 cycles at 10 A/g). Under high mass loading of 39.09 mg cm−2, the areal capacitance of PMAC700-3 based ZHSC reaches up to 4.26 F cm−2. This work provides a universal strategy to achieve multiple heteroatoms self-doped porous carbon materials from biomass for ZHSCs.
We developed a computational method to infer the complementarity-determining region 3 (CDR3) sequences of tumor-infiltrating T cells in 9,142 RNA-seq samples across 29 cancer types. We identified ...over 600,000 CDR3 sequences, including 15% that were full length. CDR3 sequence length distribution and amino acid conservation, as well as variable gene usage, for infiltrating T cells in many tumors, except in brain and kidney cancers, resembled those for peripheral blood cells from healthy donors. We observed a strong association between T cell diversity and tumor mutation load, and we predicted SPAG5 and TSSK6 as putative immunogenic cancer/testis antigens in multiple cancers. Finally, we identified three potential immunogenic somatic mutations on the basis of their co-occurrence with CDR3 sequences. One of them, a PRAMEF4 mutation encoding p.Phe300Val, was predicted to result in peptide binding strongly to both MHC class I and class II molecules, with matched HLA types in its carriers. Our analyses have the potential to simultaneously identify immunogenic neoantigens and tumor-reactive T cell clonotypes.
Airport passengers are required to put only one baggage each time in the check-in self-service so that the baggage can be detected and identified successfully. In order to automatically get the ...number of baggage that had been put on the conveyor belt, dual laser rangefinders are used to scan the outer contour of luggage in this paper. The algorithm based on hierarchical clustering and cube-fitting is proposed to inspect the number and dimension of airline luggage. Firstly, the point cloud is projected to vertical direction. By the analysis of one-dimensional clustering, the number and height of luggage will be quickly computed. Secondly, the method of nearest hierarchical clustering is applied to divide the point cloud if the above cannot be distinguished. It can preferably solve the difficult issue like crossing or overlapping pieces of baggage. Finally, the point cloud is projected to the horizontal plane. By rotating point cloud based on the centre, its minimum bounding rectangle (MBR) is obtained. The length and width of luggage are got form MBR. Many experiments in different cases have been done to verify the effectiveness of the algorithm.
The pathogen
causes tea anthracnose, resulting in economic losses to the Chinese tea industry. To effectively diagnose this pathogen in the field, we developed a loop-mediated isothermal ...amplification (LAMP) method using highly specific primers with a sensitivity of 1 pg/μl designed for amplifying the
gene, which was 10 times higher than that of conventional PCR. Additionally, to improve the method for obtaining DNA samples required for on-site diagnosis, we used the filter-disc DNA extraction method, which does not require special instruments and can be completed in a few minutes, and found that it effectively meets the requirements for the LAMP reaction. Finally, we combined LAMP with a filter-disc DNA extraction method (FDE-LAMP) to diagnose different degrees of disease in inoculated samples and 20 samples from the field. The results showed that the procedure had sufficient sensitivity for pathogen detection. Therefore, the FDE-LAMP procedure could greatly contribute to managing and preventing tea anthracnose in the field.
Understanding gene expression patterns across different human cell types is crucial for investigating mechanisms of cell type differentiation, disease occurrence and progression. The recent ...development of single-cell RNA-seq (scRNA-seq) technologies significantly boosted the characterization of cell type heterogeneities in different human tissues. However, the huge number of datasets in the public domain also posed challenges in data integration and reuse. We present Human Universal Single Cell Hub (HUSCH, http://husch.comp-genomics.org), an atlas-scale curated database that integrates single-cell transcriptomic profiles of nearly 3 million cells from 185 high-quality human scRNA-seq datasets from 45 different tissues. All the data in HUSCH were uniformly processed and annotated with a standard workflow. In the single dataset module, HUSCH provides interactive gene expression visualization, differentially expressed genes, functional analyses, transcription regulators and cell-cell interaction analyses for each cell type cluster. Besides, HUSCH integrated different datasets in the single tissue module and performs data integration, batch correction, and cell type harmonization. This allows a comprehensive visualization and analysis of gene expression within each tissue based on single-cell datasets from multiple sources and platforms. HUSCH is a flexible and comprehensive data portal that enables searching, visualizing, analyzing, and downloading single-cell gene expression for the human tissue atlas.
The poor fidelity of T4 DNA ligase has always limited the simple detection of single-nucleotide polymorphisms (SNPs) and is only applicable to some special SNP types. This study developed a highly ...sensitive and specific detection method for SNPs based on high-fidelity single-stranded circularisation. It used T4 DNA ligase and rolling circle amplification (RCA) plus loop-mediated isothermal amplification (LAMP). Surprisingly, the cyclisation stage's efficiency greatly improved. The ligation fidelity was almost perfect via the unique pairing pattern between a long-paired base at the 5′ terminus and only five bases at the 3′ terminus on linear single-stranded DNA (l-DNA). Subsequently, LR-LAMP was performed and combined with the circularisation step for the simple detection of SNPs. The results showed that even 100 aM targets could be detected correctly and that a mutation rate of 0.1% or even 0.01% could be analysed via naked-eye visualisation or fluorescence detection, respectively. In addition, genomic DNA samples were used to evaluate the method, which indicated that it could effectively distinguish the SNPs of RPA190 -T1145A in Phytophthora infestans . This strategy may play an important role in both circularisation of single-stranded DNA and detecting arbitrary SNPs.
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