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Background The relationship between pyroptosis and cancer is complex. It is controversial that whether pyroptosis represses or promotes tumor development. This study aimed to explore prognostic molecular characteristics to predict the prognosis of breast cancer (BRCA) based on a comprehensive analysis of pyroptosis-related gene expression data. Methods RNA-sequcing data of BRCA were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Ominibus (GEO) datasets. First, pyroptosis-related differentially expressed genes (DEGs) between normal and tumor tissues were identified from the TCGA database. Based on the DEGs, 1053 BRCA patients were divided into two clusters. Second, DEGs between the two clusters were used to construct a signature by a least absolute shrinkage and selection operator (LASSO) Cox regression model, and the GEO cohort was used to validate the signature. Various statistical methods were applied to assess this gene signature. Finally, Single-sample gene set enrichment analysis (ssGSEA) was employed to compare the enrichment scores of 16 types of immune cells and 13 immune-related pathways between the low- and high-risk groups. We calculated the tumor mutational burden (TMB) of TCGA cohort and evaluated the correlations between the TMB and riskscores of the TCGA cohort. We also compared the TMB between the low- and high-risk groups. Results A total of 39 pyroptosis-related DEGs were identified from the TCGA-breast cancer dataset. A prognostic signature comprising 16 genes in the two clusters of DEGs was developed to divide patients into high-risk and low-risk groups, and its prognostic performance was excellent in two independent patient cohorts. The high-risk group generally had lower levels of immune cell infiltration and lower activity of immune pathway activity than did the low-risk group, and different risk groups revealed different proportions of immune subtypes. The TMB is higher in high-risk group compared with low-risk group. OS of low-TMB group is better than that of high-TMB group. Conclusion A 16-gene signature comprising pyroptosis-related genes was constructed to assess the prognosis of breast cancer patients and its prognostic performance was excellent in two independent patient cohorts. The signature was found closely associated with the tumor immune microenvironment and the potential correlation could provide some clues for further studies. The signature was also correlated with TMB and the mechanisms are still warranted.

There has been increasing attention in using machine learning technologies, such as neural network (NN) and Gaussian process regression (GPR), to model multidimensional potential energy surfaces (PESs). NN PES features...

Background: Genomic and antigenic heterogeneity pose challenges in the precise assessment of outcomes of triple-negative breast cancer (TNBC) patients. Thus, this study was designed to investigate the cardinal genes related to cell differentiation and tumor malignant grade to advance the prognosis prediction in TNBC patients through an integrated analysis of single-cell and bulk RNA-sequencing (RNA-seq) data.Methods: We collected RNA-seq and microarray data of TNBC from two public datasets. Using single-cell pseudotime analysis, differentially expressed genes (DEGs) among trajectories from 1534 cells of 6 TNBC patients were identified as the potential genes crucial for cell differentiation. Furthermore, the grade- and tumor mutational burden (TMB)-related DEGs were explored via a weighted correlation network analysis using the Molecular Taxonomy of Breast Cancer International Consortium dataset. Subsequently, we utilized the DEGs to construct a prognostic signature, which was validated using another independent dataset. Moreover, as gene set variation analysis indicated the differences in immune-related pathways between different risk groups, we explored the immune differences between the two groups.Results: A signature including 10 genes related to grade and TMB was developed to assess the outcomes of TNBC patients, and its prognostic efficacy was prominent in two cohorts. The low-risk group generally harbored lower immune infiltration compared to the high-risk group.Conclusion: Cell differentiation and grade- and TMB-related DEGs were identified using single-cell and bulk RNA-seq data. A 10-gene signature for prognosis prediction in TNBC patients was constructed, and its performance was excellent. Interestingly, the signature was found to be closely related to tumor immune infiltration, which might provide evidence for the crucial roles of immune cells in malignant initiation and progression in TNBC.

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Background: Pancreatic adenocarcinoma (PAAD) is a highly deadly and aggressive tumour with a poor prognosis. However, the prognostic value of RNF169 and its related mechanisms in PAAD have not been elucidated. In this study, we aimed to explore prognosis-related genes, especially RNF169 in PAAD and to identify novel potential prognostic predictors of PAAD.Methods: The GEPIA and UALCAN databases were used to investigate the expression and prognostic value of RNF169 in PAAD. The correlation between RNF169 expression and immune infiltration was determined by using TIMER and TISIDB. Correlation analysis with starBase was performed to identify a potential regulatory axis of lncRNA-miRNA-RNF169.Results: The data showed that the level of RNF169 mRNA expression in PAAD tissues was higher than that in normal tissues. High RNF169 expression was correlated with poor prognosis in PAAD. In addition, analysis with the TISIDB and TIMER databases revealed that RNF169 expression was positively correlated with tumour immune infiltration in PAAD. Correlation analysis suggested that the long non-coding RNA (lncRNA) AL049555.1 and the microRNA (miRNA) hsa-miR-324-5p were involved in the expression of RNF169, composing a potential regulatory axis to control the progression of PAAD. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that RNF169 plays a role in PAAD through pathways such as TNF, Hippo, JAK-STAT and Toll-like receptor signaling.Conclusion: In summary, the upregulation of RNF169 expression mediated by ncRNAs might influence immune cell infiltration in the microenvironment; thus, it can be used as a prognostic biomarker and a potential therapeutic target in PAAD.

The reactive collisions of nitrogen ion with hydrogen and its isotopic variations have great significance in the field of astrophysics. Herein, the state-to-state quantum time-dependent wave packet calculations of N+(3P) + HD → NH+/ND+ + D/H reaction are carried out based on the recently developed potential energy surface [Phys. Chem. Chem. Phys., 2019, 21, 22203]. The integral cross sections (ICSs) and rate coefficients of both channels are precisely determined at the state-to-state level. The results of total ICSs and rate coefficients present a dramatic preference on the ND+ product over the NH+ product, conforming to the long-lived complex-forming mechanism. Product state-resolved ICSs indicate that both the product molecules are difficult to excite to higher vibrational states, and the ND+ product has a hotter rotational state distribution. Moreover, the integral cross sections and rate coefficients are precisely determined at the state-to-state level and insights are provided about the differences between the two channels. The present results would provide an important reference for the further experimental studies at the finer level for this interstellar chemical reaction. The datasets presented in this paper, including the ICSs and rate coefficients of the two products for the title reaction, are openly available at https://www.doi.org/10.57760/sciencedb.j00113.00034 (https://www.scidb.cn/s/rEju22).

Background: The invention and development of single-cell technologies have contributed a lot to the understanding of tumor heterogeneity. The objective of this research was to investigate the differentially expressed genes (DEGs) between normal and tumor cells at the single-cell level and explore the clinical application of these genes with bulk RNA-sequencing data in breast cancer.Methods: We collected single-cell, bulk RNA sequencing (RNA-seq) and microarray data from two public databases. Through single-cell analysis of 23,909 mammary gland cells from seven healthy donors and 33,138 tumor cells from seven breast cancer patients, cell type-specific DEGs between normal and tumor cells were identified. With these genes and the bulk RNA-seq data, we developed a prognostic signature and validated the efficacy in two independent cohorts. We also explored the differences of immune infiltration and tumor mutational burden (TMB) between the different risk groups.Results: A total of 6,175 cell-type-specific DEGs were obtained through the single-cell analysis between normal and tumor cells in breast cancer, of which 1,768 genes intersected with the bulk RNA-seq data. An 18-gene signature was constructed to assess the outcomes in breast cancer patients. The efficacy of the signature was notably prominent in two independent cohorts. The low-risk group showed higher immune infiltration and lower TMB. Among the 18 genes in the signature, 16 were also differentially expressed in the bulk RNA-seq dataset.Conclusion: Cell-type-specific DEGs between normal and tumor cells were identified through single-cell transcriptome data. The signature constructed with these DEGs could stratify patients efficiently. The signature was also closely correlated with immune infiltration and TMB. Nearly all the genes in the signature were also differentially expressed at the bulk RNA-seq level.