Long non-coding RNA (lncRNA) is a prognostic biomarker for many types of cancer. Here, we aimed to study the prognostic value of lncRNA in Breast Invasive Carcinoma (BRCA). We downloaded expression profiles from The Cancer Genome Atlas (TCGA) datasets. Subsequently, we screened the differentially expressed genes between normal tissues and tumor tissues. Univariate Cox, LASSO regression, and multivariate Cox regression analysis were used to construct a lncRNA prognostic model. Finally, a nomogram based on the lncRNAs model was developed, and weighted gene co-expression network analysis (WGCNA) was used to predict mRNAs related to the model, and to perform function and pathway enrichment. We constructed a 6-lncRNA prognostic model. Univariate and multivariate Cox regression analysis showed that the 6-lncRNA model could be used as an independent prognostic factor for BRCA patients. We developed a nomogram based on the lncRNAs model and age, and showed good performance in predicting the survival rates of BRCA patients. Also, functional pathway enrichment analysis showed that genes related to the model were enriched in cell cycle-related pathways. Tumor immune infiltration analysis showed that the types of immune cells and their expression levels in the high-risk group were significantly different from those in the low-risk group. In general, the 6-lncRNA prognostic model and nomogram could be used as a practical and reliable prognostic tool for invasive breast cancer.
Oncolytic viruses have the capacity to selectively kill infected tumor cells and trigger protective immunity. As such, oncolytic virotherapy has become a promising immunotherapy strategy against cancer. A variety of viruses from different families have been proven to have oncolytic potential. Senecavirus A (SVA) was the first picornavirus to be tested in humans for its oncolytic potential and was shown to penetrate solid tumors through the vascular system. SVA displays several properties that make it a suitable model, such as its inability to integrate into human genome DNA and the absence of any viral-encoded oncogenes. In addition, genetic engineering of SVA based on the manipulation of infectious clones facilitates the development of recombinant viruses with improved therapeutic indexes to satisfy the criteria of safety and efficacy regulations. This review summarizes the current knowledge and strategies of genetic engineering for SVA, and addresses the current challenges and future directions of SVA as an oncolytic agent.
Ferroptosis is a new form of iron-dependent cell death and plays an important role during the occurrence and development of various tumors. Increasingly, evidence shows a convincing interaction between ferroptosis and tumor immunity, which affects cancer patients’ prognoses. These two processes cooperatively regulate different developmental stages of tumors and could be considered important tumor therapeutic targets. However, reliable prognostic markers screened based on the combination of ferroptosis and tumor immune status have not been well characterized. Here, we chose the ssGSEA and ESTIMATE algorithms to evaluate the ferroptosis and immune status of a TCGA breast invasive ductal carcinoma (IDC) cohort, which revealed their correlation characteristics as well as patients’ prognoses. The WGCNA algorithm was used to identify genes related to both ferroptosis and immunity. Univariate COX, LASSO regression, and multivariate Cox regression models were used to screen prognostic-related genes and construct prognostic risk models. Based on the ferroptosis and immune scores, the cohort was divided into three groups: a high-ferroptosis/low-immune group, a low-ferroptosis/high-immune group, and a mixed group. These three groups exhibited distinctive survival characteristics, as well as unique clinical phenotypes, immune characteristics, and activated signaling pathways. Among them, low-ferroptosis and high-immune statuses were favorable factors for the survival rates of patients. A total of 34 differentially expressed genes related to ferroptosis-immunity were identified among the three groups. After univariate, Lasso regression, and multivariate stepwise screening, two key prognostic genes (GNAI2, PSME1) were identified. Meanwhile, a risk prognosis model was constructed, which can predict the overall survival rate in the validation set. Lastly, we verified the importance of model genes in three independent GEO cohorts. In short, we constructed a prognostic model that assists in patient risk stratification based on ferroptosis-immune-related genes in IDC. This model helps assess patients’ prognoses and guide individualized treatment, which also further eelucidatesthe molecular mechanisms of IDC.
Background: The pathogenesis of chronic pancreatitis is still unclear. Trypsinogen activation is an active factor in acute pancreatitis that has not been studied in the occurrence of chronic pancreatitis. Methods: Immunofluorescence was used to detect the location and expression of trypsinogen in chronic pancreatitis and normal tissues. Microarray and single-cell RNA-seq (scRNA-seq) were used to screen core genes and pathways in pancreatic stellate cells (PSCs). Western blotting and immunofluorescence were used to verify trypsinogen expression in PSCs after silencing Rabep1. Immunofluorescence and flow cytometry were used to validate trypsinogen activation and PSC activation after intervening in the endocytosis pathway. Results: Endocytosed trypsinogen was found in PSCs in CP clinical samples. Bioinformatic analysis showed that Rabep1 is a core gene that regulates trypsinogen endocytosis through the endocytosis pathway, verified by Western blot and immunofluorescence. Immunofluorescence and flow cytometry analyses confirmed the activation of trypsinogen and PSCs through the endocytosis pathway in PSCs. Conclusion: This study discovered a new mechanism by which trypsinogen affects the activation of PSCs and the occurrence and development of CP. Through communication between pancreatic acinar cells and PSCs, trypsinogen can be endocytosed by PSCs and activated by the Rabep1 gene.
Background:Breast cancer (BC) is one of the most common tumors in women. Recent years, immune checkpoint inhibitors (ICIs) have brought good news to BC patients. Although significant achievements have been made through treatment with ICIs, some people who experience serious immune-related adverse events (IrAEs) are still insensitive to this approach. The response to ICI treatment depends on the type of tumor microenvironment (TME). Methods:WGCNA (weighted gene co-expression network analysis), ESTIMATE algorithm, LASSO regression analysis, survival analysis, functional enrichment analysis are conducted to analyze the BC data in the TCGA database. Immunohistochemistry was used to verify the expression of CD52 in BC.Results:WGCNA and ESTIMATE algorithm found that the CD52 is closely related to the immune microenvironment. CD52 highly expressed in various breast cancer subtypes, and patients with high expression of CD52 have longer survival time. Compared with the low-CD52 group, the high-CD52 group had more immune cell infiltration. TIMER database verification results showed that CD8+ T cells, activated memory CD4 T cells, memory B cells, γδ T cells, and Tregs were positively correlated with CD52 expression, while M2 macrophages were negatively correlated. CD52 can change the trend of TIC (CD8+ T) and tumor-associated macrophage (TAM) infiltration with respect to the survival time of breast cancer patients. Based on the expression of CD52, we explored the relationship between CD52 and the adaptive immune response (AIR). CD52 is a marker of AIR stratification in breast cancer patients. We constructed a CD52-related adaptive immune response gene signature (CD52rAIRGsig) which is an independent prognostic factor for breast cancer and related to genome instability and the immune cells infiltration in the TME. CD52 and CD52rAIRGsig were associated with PD-1 signaling and immune checkpoint inhibitor markers, which proves that patients with high CD52 expression and low risk of CD52rAIRGsig are more suitable for ICI treatment. We then screened chemotherapeutics for personalized medicine based on CD52rAIRGsig. Conclusion:Therefore, we have discovered a new marker to guide the treatment and prognosis of breast cancer patients with ICIs. This provides a combined treatment strategy including different combinations of ICIs combined with chemotherapeutic drugs to treat breast cancer.
BACKGROUND The biliary system and related diseases have been one of the key research objects of digestive system diseases, and intestinal microecology has been a hot topic in recent years. Bile entering the intestine through the biliary system has been proven to have an important relationship with the biodiversity of intestinal flora, and the homeostasis of intestinal microecology will also change with the occurrence of biliary diseases. OBJECTIVE The aim of this study is to summarize studies on the combination of the biliary system and intestinal microecology, in order to explore the research history, present situation and future trend of the study on the combination of biliary system and intestinal microecology. METHODS The literatures from 2000-01-01 to 2022-02-28 in the Web of Science core database were searched, and 180 articles were screened according to the inclusion criteria. HistCite Pro and VOSviewer software were used to analyze the relevant indicators of bibliometrics and draw knowledge maps. Microsoft Excel 2019 was used for charting. RESULTS Through a bibliometric analysis of 180 papers. From 2000-01-01 to 2002-02-28, especially since 2013, the number of articles published in this field has been increasing. The global citation score (GCS) of the articles was 4751, with an average of 26.39 citations per article. The local citation score (LCS) is 89. At present, "SCIENTIFIC REPORTS" is the journal with the most publications, and “GUT” is the most authoritative journal in this field. The United States plays a leading role in global research, , and China is developing rapidly. The research of Karlsen TH, Schnabl B and Brenner DA in this field has been widely recognized. CONCLUSIONS At present and in the future, research will focus on the intestinal microecology itself. How to simulate the natural intestinal microecology or develop intestinal microecological agents for the benefit of patients with biliary tract diseases is widely considered.
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