Immune checkpoint blockade (ICB) therapy has achieved breakthroughs in the treatment of advanced non-small cell lung cancer (NSCLC). Nevertheless, the low response due to immuno-cold tumor microenvironment (TME) largely limits the application of ICB therapy. Based on the glycolytic/cholesterol synthesis axis, a stratification framework for EGFR wild-type NSCLC was developed to summarize the metabolic features of immuno-cold and immuno-hot tumors. The cholesterol subgroup displays the worst prognosis in immuno-cold NSCLC with significant enrichment of the cholesterol gene signature, indicating targeting cholesterol synthesis is essential for the therapy for immuno-cold NSCLC. Statin, the inhibitor for cholesterol synthesis, can suppress the aggressiveness of NSCLC in vitro and in vivo and also drastically reverse immuno-cold to an inflamed phenotype in vivo which exhibited a higher response to ICB therapy. Moreover, both our in-house data and meta-analysis further support that statin can significantly enhance ICB efficacy. In terms of preliminary mechanisms, statin could transcriptionally inhibit PD-L1 expression and induce ferroptosis in NSCLC cells. Overall, we reveal the significance of cholesterol synthesis in NSCLC and demonstrate the improved therapeutic efficacy of ICB in combination with statin.These findings could provide a innovative clinical insight to treat NSCLC patients with immuno-cold tumors.
BackgroundN6-methyladenosine (m6A) is the most abundant internal mRNA modification in eukaryotic cells. There is accumulating evidence that m6A methylation can play a significant role in the early diagnosis and treatment of cancers. However, the mechanism underlying the involvement of m6A in cervical cancer remains unclear.MethodsHere, we examined the m6A modification patterns of immune cells in the tumour microenvironments (TMEs) of 306 patients with cervical cancer from The Cancer Genome Atlas dataset and analysed the relations between them according to 32 m6A regulators. Immune infiltration in the TME of cervical cancer was analysed using the CIBERSORT algorithm and single-sample gene set enrichment analysis. The m6Ascore was structured though principal component analysis.ResultsTwo different m6A modification patterns were detected in 306 patients with cervical cancer, designated as m6Acluster A and B. The immune cell infiltration characteristics and biological behaviour differed between the two patterns, with m6Acluster A showing a higher level of immune infiltration. The samples were also divided into two genomic subtypes according to 114 m6A regulatory genes shown to be closely correlated with prognosis on univariate Cox regression analysis. Survival analysis showed that gene cluster B was related to better survival than gene cluster A. Most of the m6A regulators showed higher expression in gene cluster B than in gene cluster A. Single-sample gene set enrichment analysis indicated a higher level of immune cell infiltration in gene cluster A. The m6Ascore signature was examined to determine the m6A modification patterns in cervical cancer. Patients with a high m6Ascore showed better survival, while the low m6Ascore group had a higher mutation frequency and better response to treatment.ConclusionsThis study showed that m6A modification patterns play important roles in cervical cancer. Analysis of m6A modification patterns will yield an improved understanding of the TME in cervical cancer, and facilitate the development of better immunotherapy strategies.
The rapid development of computer and network has promoted the emergence and development of new teaching methods and teaching media. This paper takes the computer distance virtual experiment teaching as the research goal, by literature investigation, summarization and case analysis methods, basing on analysis of computer distance teaching, Virtual Reality (VR) technology, virtual experiment teaching, and other related technology theories, the paper proposes a computer distance virtual experiment teaching mode based on VR technology. By taking the virtual computer assembly experiment as an example, this paper designs a computer distance virtual experiment teaching mode based on VR technology, realizes the computer distance virtual experiment teaching of the computer assembly experiment, and verifies the feasibility of the teaching mode. The research results indicate that, this teaching mode has a certain practical significance on improving the computer distance teaching mode and promoting the smooth development of computer distance teaching.
Background: The non-receptor protein tyrosine phosphatase (PTPN) gene family has been considered to be involved in the oncogenesis and development of multiple cancers. However, its prognostic utility and immunological relevance in breast cancer (BrCa) have not been clarified.Methods: A transcriptional level interpretation of the expressions and prognostic values was analyzed using the data from The Cancer Genome Atlas (TCGA) cohort. In addition, GO and DAVID pinpoint the functional enrichment of PTPNs. Moreover, the immune correlations of PTPN7 in BrCa and pan-cancer were further investigated based on the TCGA cohort and were testified using the in-house and the Gene Expression Omnibus (GEO) cohorts.Results: For systematic analysis of the PTPN family, we found that the expression levels of PTPN1, PTPN6, PTPN7, PTPN18, PTPN20, and PTPN22 was promoted in tumor tissues while comparing with paraneoplastic tissues during our study. We further investigated their functions and protein-protein interactions (PPI), and these results strongly suggested that PTPN family was associated with protein dephosphorylation. Next, we performed an immunological relevance analysis and found that PTPN7 was correlated with immune infiltration, suggesting a stronger association of PTPN7 with immuno-hot tumors in BrCa. In addition, results from the in-house cohort confirmed the positive correlation between PTPN7 and PD-L1. The pan-cancer analysis revealed that PTPN7 was related to PD-L1 and CTLA-4 expression in almost all cancer types. Finally, the predictive value of PTPN7 for immunotherapy was significant in two independent GEO cohorts.Conclusion: In conclusion, this is the first extensive research on the correlation between PTPN family expression and immune characterization in BrCa. As results, PTPN7 expression is associated with immuno-hot tumors and could be a promising predictive biomarker for immunotherapy in not only BrCa but multiple cancers.
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