Background: Metabolic reprogramming, immune evasion and tumor-promoting inflammation are three hallmarks of cancer that provide new perspectives for understanding the biology of cancer. We aimed to figure out the relationship of tumor glycolysis and immune/inflammation function in the context of breast cancer, which is significant for deeper understanding of the biology, treatment and prognosis of breast cancer. Methods: Using mRNA transcriptome data, tumor-infiltrating lymphocytes (TILs) maps based on digitized H&Estained images and clinical information of breast cancer from The Cancer Genome Atlas projects (TCGA), we explored the expression and prognostic implications of glycolysis-related genes, as well as the enrichment scores and dual role of different immune/inflammation cells in the tumor microenvironment. The relationship between glycolysis activity and immune/inflammation function was studied by using the differential genes expression analysis, gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, gene set enrichment analyses (GSEA) and correlation analysis. Results: Most glycolysis-related genes had higher expression in breast cancer compared to normal tissue. Higher phosphoglycerate kinase 1 (PGK1) expression was associated with poor prognosis. High glycolysis group had upregulated immune/inflammation-related genes expression, upregulated immune/inflammation pathways especially IL-17 signaling pathway, higher enrichment of multiple immune/inflammation cells such as Th2 cells and macrophages. However, high glycolysis group was associated with lower infiltration of tumor-killing immune cells such as NKT cells and higher immune checkpoints expression such as PD-L1, CTLA4, FOXP3 and IDO1. Conclusions: In conclusion, the enhanced glycolysis activity of breast cancer was associated with pro-tumor immunity. The interaction between tumor glycolysis and immune/inflammation function may be mediated through IL-17 signaling pathway.
Objective : To evaluate the efficacy and safety of Hua Shi Bai Du Granule (Q-14) plus standard care compared with standard care alone in adults with coronavirus disease (COVID-19). Study Design : A single-center, open-label, randomized controlled trial. Setting : Wuhan Jinyintan Hospital, Wuhan, China, February 27 to March 27, 2020. Participants : A total of 204 patients with laboratory-confirmed COVID-19 were randomized into the treatment group and control group, consisting of 102 patients in each group. Interventions : In the treatment group, Q-14 was administered at 10 g (granules) twice daily for 14 days, plus standard care. In the control group, patients were provided standard care alone for 14 days. Main Outcome Measure : The primary outcome was the conversion time for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral assay. Adverse events were analyzed in the safety population. Results : Among the 204 patients, 195 were analyzed according to the intention-to-treat principle. A totalof 149 patients (71 vs. 78 in the treatment and control groups, respectively) tested negative via the SARS-CoV-2 viral assay. There was no statistical significance in the conversion time between the treatment group and control group (full analysis set: median (interquartile range): 10.00 (9.00-11.00) vs. 10.00 (9.00-11.00); mean rank: 67.92 vs. 81.44; P=0.051.). The recovery time for fever was shorter in the treatment group than in the control group. The disappearance rate of symptomslike cough, fatigue, and chest discomfort was significantly higher in the treatment group. In chest computed tomography (CT) examinations, the overall evaluation of chest CT examination after treatment compared with baseline showed that more patients showed improvement in the treatment group. There were no significant differences in the other outcomes. Conclusion : The combination of Q-14 and standard care for COVID-19 was useful for the improvement of symptoms (such as fever, cough, fatigue, and chest discomfort), but did not result in a significantly higher probability of negative conversion in the SARS-CoV-2 viral assay. No serious adverse events were observed. Trial Registration : ChiCTR2000030288
Background: Tumor microenvironment is essential for breast cancer progression and metastasis. Our study sets out to examine the genes affecting stromal and immune infiltration in breast cancer progression and prognosis. Materials and Methods: This work provides an approach for quantifying stromal and immune scores by using ESTIMATE algorithm based on gene expression matrix of breast cancer patients in TCGA database. We found differentially expressed genes (DEGs) through limma R package. Functional enrichments were accessed through Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Besides, we constructed a protein-protein network, identified several hub genes in Cytoscape, and discovered functionally similar genes in GeneMANIA. Hub genes were validated with prognostic data by Kaplan-Meier analysis both in The Cancer Genome Atlas (TCGA) database and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) database and a meta-analysis of hub genes prognosis data was utilized in multiple databases. Furthermore, their relationship with infiltrating immune cells was evaluated by Tumor IMmune Estimation Resource (TIMER) web tool. Cox regression was utilized for overall survival (OS) and recurrence-free survival (RFS) in TCGA database and OS in METABRIC database in order to evaluate the impact of stromal and immune scores on patients prognosis. Results: One thousand and eighty-five breast cancer patients were investigated and 480 differentiated expressed genes (DEGs) were found based on the analysis of mRNA expression profiles. Functional analysis of DEGs revealed their potential functions in immune response and extracellular interaction. Protein-protein interaction network gave evidence of 10 hub genes. Some of the hub genes could be used as predictive markers for patients prognosis. In this study, we found that tumor purity and specific immune cells infiltration varied in response to hub genes expression. The multivariate cox regression highlighted the fact that immune score played a detrimental role in overall survival (HR = 0.45, 95% CI: 0.27-0.74, p = 0.002) and recurrence-free survival (HR = 0.41, 95% CI: 0.22-0.77, p = 0.006) in TCGA database. These result was confirmed in Xu et al. Tumor Microenvironment in Breast Cancer METABRIC database that immune score was a protector of OS (HR = 0.88, 95% CI: 0.77-0.99, p = 0.039). Conclusions: Our findings promote a better understanding of the potential genes behind the regulation of tumor microenvironment and cells infiltration. Immune score should be considered as a prognostic factor for patients' survival.
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