In view of the high infection rate of Helicobacter pylori, a safe and effective vaccine is urgently needed. Recent trends in vaccine design have shifted toward safe and specific epitope‐based vaccines. In this study, by using different immunoinformatics approaches, a total of eight linear B cell epitopes, four HTL and three CTL epitopes of FlaA and UreB proteins of H. pylori G27 strain were screened out, we also predicted the conformational epitopes of the two proteins. Then, the dominant epitopes were sequentially linked by appropriate linkers, and the cytotoxic T lymphocyte–associated antigen 4 extracellular domain was attached to the N‐terminal of the epitope sequence. Meanwhile, molecular docking, molecular dynamics simulations and principal component analysis were performed to show that the multi‐epitope vaccine structure had strong interactions with B7 (B7‐1, B7‐2) and Toll‐like receptors (TLR‐2, ‐4). Eventually, the effectiveness of the vaccine was validated using in silico cloning. These analyses suggested that the designed vaccine could target antigen‐presenting cells and had high potency against H. pylori, which could provide a reference for the future development of efficient H. pylori vaccines.
Background Cervical cancer (CC) is the fourth most frequent cancer in women worldwide, Patients with CC, those at an advanced stage or with recurrent disease, have a poor prognosis with limited treatment options. Cuproptosis, which is regulated by mitochondrial ferredoxin 1-mediated protein lipoylation, is a newly discovered form of cell death. This study aimed to explore the potential prognostic value of cuproptosis-related lncRNAs and their relationship to immune microenvironment in cervical cancer.Methods RNA-sequencing data and clinical data of female cervical cancer patients were obtained from The Cancer Genome Atlas (TCGA), and 19 cuproptosis-related genes were obtained from cuproptosis-related studies. 304 CC patients were randomly separated into training or validation cohorts in a 1:1 ratio. Pearson correlation analysis was used to screen out the lncrnas associated with copper-copper mineralization, and correlation analysis was conducted with 711 reported cuproptosis-related lncRNAs. Univariate, LASSO and multivariate Cox regression analyses were used to construct the characteristics of cuproptosis-related lncRNAs in the training cohort, and their prognostic value was further tested in the validation cohort. Patients were divided into high-and low-risk groups based on the median risk score. Independent prognostic analyses, ROC, C-index, and nomogram were carried out to assess the prognostic value of the signature. Subsequently, lncRNAs were analyzed for Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes Enrichment (KEGG), immune-related functions, and tumour mutation burden (TMB). Finally, we used tumor immune dysfunction and exclusion (TIDE) algorithms on immune escape and immunotherapy of cuproptosis-related lncRNAs for CC.Results A total of 10 cuproptosis-related lncRNAs were obtained, and patients were divided into high-and low-risk groups. We found that high-risk patients had worse overall survival (OS) and progression-free survival (PFS) and higher mortality. Independent prognostic analyses, ROC, C-index, and nomogram showed that the cuproptosis-related lncRNAs can accurately predict the prognosis of patients. The nomogram and heatmap showed a distinct distribution of the high- and low-risk cuproptosis-related lncRNAs. Enrichment analysis showed that the biological functions of lncRNAs are associated with tumor development. Tumor immune microenvironmental analyses the risk score was positively correlated with the number of M0 macrophages, and mast cell activated, negatively correlated with Dendritic cells resting, M1 macrophages, mast cell resting, T cell CD4 memory activated, T cell gamma delta and T cells CD8. we analyzed immune-related functions to evaluate the immune status of the low-risk and high-risk groups, and the results showed that HLA, cytolytic activity, inflammation-promoting, check point, T-cell co-inhibition, APC co-inhibition, APC co-stimulation, CCR, MHC-I, and type I IFN response were significantly more active in the low-risk group than in the high-risk group (p > 0.05). The results of the expression levels of immune checkpoint molecules in high-risk group and low-risk group showed that the expression levels of common immune checkpoint molecules such as PDCD1, CD274, HAVCR2, CTLA4, and TIGIT in low-risk group were all higher than those in high-risk group. In terms of TME scores, immune scores and ESTIMATE scores were higher in low-risk patients than in high-risk patients, with no difference in stromal scores between them, suggesting a higher infiltration of immune cells in the low-risk group. In addition, OS was poorer in patients with low TMB. We were surprised to find that there was a negative correlation between the TIDE and risk scores, further suggesting that high-risk patients might react more actively to immunotherapy.Conclusion We identified a novel cuproptosis-related lncRNA signature which could precisely predict the prognosis of cervical cancer patients. Cuproptosis -related lncRNAs may may provide new insights into clinical applications and immunotherapy.
Background: In this work, the sialic acid-binding Ig-like lectin 9 (SIGLEC9) was used to examine the diagnostic utility and underlying processes of cervical cancer. Methods: The TNM plot database were used to analyze the association of SIGLEC9 expression levels in normal, tumor and metastatic. Immunohistochemical Staining and western blotting of SIGLEC9 were performed in 40 cervical cancer patients and 30 patients with uterine fibroids. Moreover, we analyzed the correlation between SIGLEC9 and tumor markers. Furthermore, signaling pathways linked to SIGLEC9 expression were discovered using the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes Enrichment (KEGG), and Gene Set Enrichment Analysis (GSEA). The relative immune cell infiltrations of each sample were assessed using the estimate method and the CIBERSORT algorithm. We verified the relationship between SIGLEC9 and Treg by immunohistochemistry. Then we revealed how SIGLEC9 functions in macrophages through single-cell analysis. Moreover, we collected some genes directly interacting with SIGLEC9 from four protein-interaction network databases. In addition, we used the the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus database (GEO) databases to analyze the association of MUC1 expression levels with tumor stages. We know 20 kinds of sialyltransferases, and their expressions in cervical cancer were analyzed by TCGA database, and verified by GEO database. Lastly, immunohistochemical staining of MUC1 and ST3GAL1 was performed in 40 cervical cancer patients. And we used ROC to analyze the diagnostics of SIGLEC9, MUC1, ST3GAL1, and ST6GAL1 in cervical cancer. Results: SIGLEC9 is strongly expressed in cervical cancer. The immunohistochemical staining and Western blotting of tissue sections from 40 cervical cancer patients and 30 patients with uterine fibroids showed that SIGLEC9 was highly expressed in cervical cancer. Moreover, SIGLEC9 was associated with the tumor marker CA125 by forest map. Furthermore, the SIGLEC9 expression level was positively correlated with Treg activation by the estimate method and the CIBERSORT algorithm. Immunohistochemistry verified that siglec9 was positively correlated with Treg. SIGLEC9 expression was also positively correlated with major immune checkpoints. Through single-cell analysis, we found that the SIGLEC9 gene is related to the ability of macrophages to process antigens. Furthermore, the PPI analysis showed that SIGLEC9 was correlated with MUC1. TCGA databases showed that MUC1 was highly expressed in the cervical cancer group. According to TCGA and GEO databases, ST3GAL-I and ST6GAL-I are highly expressed in cervical cancer. And immunohistochemical staining of MUC1 and ST3GAL1 was highly expressed in cervical cancer patients. Lastly, SIGLEC9, MUC1, ST3GAL1, and ST6GAL1 have high diagnostic values by ROC. Conclusion: These findings imply that SIGLEC9 is a cervical cancer diagnostic marker and may one day be used as an immunotherapy target for cervical cancer patients.
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