Abstract Background: The study aims to investigate the expression level of Thrombospondin 2 (TSP2) in Gastric Cancer (GC) and determine the relationship between TSP2 and clinical characteristics and prognosis. Methods: The online database Gene Expression Profile Interactive Analysis (GEPIA) was used to analyze the mRNA expression level of TSP2 in GC. The Kaplan-Meier plotter prognostic analysis tool was used to evaluate the influence of TSP2 expression on clinical prognosis in GC patients. The expression level of TSP2 was analyzed in paraffin-embedded GC samples and adjacent normal tissues by immunohistochemistry. The relationship between clinicopathological characteristics and prognosis of GC patients. Next, the relationship between clinicopathological characteristics and prognosis of GC patients was assessed. Transwell experiment was used to evaluate the effect of TSP2 on the invasion and migration of HGC27 and AGS cells. Results: Compared with normal tissues, the expression of TSP2 mRNA in GC was significantly up-regulated, and it was closely related to the clinical stage of GC. The high expression of TSP2 significantly affected the OS, FP and PPS of patients with GC. Among them, the expression level of TSP2 did not affect the prognosis of patients with GC in N0 subgroup, but significantly affected the prognosis of patients with GC in N (1+2+3)subgroup. The protein expression level of TSP2 in GC tissue was significantly higher than in normal tissues (P<0.01). The overall survival (OS) rate of patients with high TSP2 expression was lower than the low TSP2 expression group ( P =0.013). Knockdown of TSP2 can significantly inhibit the growth of GC cells. Proliferation, migration, invasion ability, and TSP2 expression level significantly correlate with mismatch repair genes such as PMS2, MSH6, MSH2, and MLH1 ( P <0.05). Conclusion : The expression of TSP2 in GC is significantly increased, closely related to the metastasis and mismatch repair process of GC patients and affected GC patients' prognosis. It is a potential marker and treatment target for the prognosis of GC patients.
Background: An increasing number of studies had shown that tertiary lymphoid structure (TLS) plays an important role in tumor progression.However, the prognostic role of TLS in various tumors remains controversial.This meta-analysis aims to investigate the clinicopathological and prognostic values of TLS in solid tumors.Methods: A systematic search was conducted in PubMed, EMBASE and Cochrane Library undated to November 2, 2020.Odds ratios of clinical parameters, hazard ratio (HR) of overall survival (OS), relapse-free survival (RFS), disease-free survival (DFS) and relapse rate were calculated in order to evaluate the relationship between TLS expression and clinicopathological or prognostic values in different tumors.Result: 27 eligible studies including 6647 patients with different types of tumors were analyzed.High TLS expression was associated with a longer OS (HR = 0.66, 95% CI: 0.50 -0.86, P = 0.002) and RFS (HR = 0.61, 95% CI: 0.47 -0.79, P = 0.0001).Moreover, high TLS levels in tumor were associated with a low risk of recurrence (HR = 0.43, 95% CI: 0.32 -0.57, P < 0.0001).However, there was no relationship between TLS expression and DFS.Meanwhile, high TLS expression was associated with smaller tumor size (P < 0.00001) and higher tumor infiltrating lymphocytes (TILs).Furthermore, the subgroup analysis showed high TLS expression that may be associated with a lower clinical grading and N stage in breast cancer and colorectal cancer.Conclusion: High TLS expression is associated with the longer OS and RFS in solid tumors, and a lower risk of cancer relapse.Meanwhile, high TLS expression is also associated with a smaller tumor size, higher infiltration of TILs, lower clinical grading and N stage in the tumor.Therefore, high TLS expression in the tumor is a favorable prognostic biomarker for solid tumor patients.
Background: Long noncoding RNA KCNQ1 opposite strand/antisense transcript 1 (lncRNA KCNQ1OT1) is abnormally expressed in various solid tumors.The purpose of this study was to explore the prognostic value and potential functional role of lncRNA KCNQ1OT1 across cancers.Methods: We performed a meta-analysis of published literature to evaluate the prognostic value of lncRNA KCNQ1OT1 across cancers.Verification, functional analysis, and genomic variation analysis were performed using the GEPIA, TIMER, and LnCeVar databases.According to the immune cell infiltration level, we established a prognostic model of lncRNA KCNQ1OT1 expression using public datasets of TIMER.We used quantitative real-time polymerase chain reaction (RT-qPCR) and western blot to detect the expression levels of lncRNA KCNQ1OT1 and the CD155 protein in colorectal cancer (CRC) tissues and cell lines.Then, a lncRNA KCNQ1OT1-knockdown cell line was cocultured to explore the role of lncRNA KCNQ1OT1 and CD155 in the T cell response by flow cytometric analysis.Results: Our results showed that the high expression of lncRNA KCNQ1OT1 was significantly related to poor overall survival across cancers, especially CRC.Interestingly, we found that COAD patients with high lncRNA KCNQ1OT1 expression and high CD8 + T cell infiltration levels had a worse prognosis than those with low lncRNA KCNQ1OT1 expression and high CD8 + T cell infiltration levels.Moreover, lncRNA KCNQ1OT1 and CD155 showed significantly higher expression in CRC tissue than in normal tissue, and lncRNA KCNQ1OT1 expression was positively correlated with CD155 expression in CRC.Finally, knockdown of lncRNA KCNQ1OT1 reduced CD155 expression in HCT116 and SW620 cells and enhanced the immune response in coculture with CD8 + T cells.Conclusions: High lncRNA KCNQ1OT1 expression is significantly correlated with poor prognosis of CRC patients and mediates the CD8 + T cell response in CRC.These findings indicate that lncRNA KCNQ1OT1 is a prognostic biomarker and potential immune therapeutic target for enhancing the CD8 + T cell response in CRC.
Abstract Background This study aims to investigate thrombospondin 2 (TSP2) expression levels in gastric cancer (GC) and determine the relationship between TSP2 and clinical characteristics and prognosis. Methods The online database Gene Expression Profile Interactive Analysis (GEPIA) was used to analyse TSP2 mRNA expression levels in GC. The Kaplan–Meier plotter prognostic analysis tool was used to evaluate the influence of TSP2 expression on clinical prognosis in GC patients. TSP2 expression levels were analysed in paraffin-embedded GC samples and adjacent normal tissues by immunohistochemistry. The relationship between the clinicopathological characteristics and prognosis of GC patients was assessed. Transwell experiments were used to evaluate the effect of TSP2 on HGC27 and AGS cell invasion and migration. The EdU experiment was used to detect the effect of transfection of TSP2 on cell proliferation, and the flow cytometry experiment was used to detect the effect of TSP2 on cell apoptosis and the cell growth cycle. Western blotting (Wb) technology was used to detect MMP, E-cadherin, N-cadherin, Vimentin, Snail, AKT, PI3K, and VEGF protein expression in HGC27 cells. Results Compared with normal tissues, TSP2 mRNA expression in GC was significantly upregulated and was closely related to the clinical stage of GC. High TSP2 expression significantly affected the OS, FP and PPS of patients with GC. Among these patients, TSP2 expression levels did not affect the prognosis of patients with GC in the N0 subgroup but significantly affected the prognosis of patients with GC in the N (1 + 2 + 3) subgroup. TSP2 protein expression levels were significantly higher in GC tissue compared with normal tissues ( P < 0.01). The overall survival (OS) and relapse-free survival (RFS) of patients with high TSP2 expression were lower than those of patients with low TSP2 expression. Cells transfected with the TSP2-silencing sequence exhibited increased apoptosis and inhibition of proliferation, migration and invasion. AKT and PI3K expression in cells was significantly downregulated ( P < 0.01). AKT, PI3K and VEGF expression in cells transfected with the TSP2 silencing sequence was significantly reduced. Proliferation, migration, invasion ability, and TSP2 expression levels significantly correlated with mismatch repair genes, such as PMS2, MSH6, MSH2, and MLH1 ( P < 0.05). Conclusion TSP2 expression is significantly increased in GC. TSP2 expression is closely related to metastasis and the mismatch repair process in GC patients and affects GC patient prognosis. The mechanism may involve regulating gastric cancer cell proliferation and migration by modulating the VEGF/PI3K/AKT signalling pathway. TSP2 is a potential marker and therapeutic target for the prognosis of GC patients.
Colorectal cancer (CRC) is the third most prevalent cancer globally. In the treatment of CRC, surgical resection is commonly adopted, and neoadjuvant chemotherapy or immunotherapy is mainly administered for patients with advanced disease. However, despite the developments in the field of cancer treatment, the mortality rate of CRC has remained high. Therefore, novel treatments for CRC need to be explored. Astragalus membranaceus, commonly known in China as Huangqi (HQ), a traditional Chinese medicine, has been reported to be a potential antitumorigenic agent. This study aimed to investigate the mechanisms of action of HQ.Active ingredients and putative targets of HQ were obtained through a comprehensive search of the Traditional Chinese Medicine Systems Pharmacology database. CRC-related targets were retrieved from the GeneCards database and then overlapping targets were acquired. After visualization of the compound-disease network and protein-protein interaction (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of the overlapping genes were performed. Additionally, HCT116 cells were treated with the active components of HQ at a 20-µM concentration. Cell Counting Kit-8 was used to detect cell activity, and real-time quantitative polymerase chain reaction was carried out to detect the expression of genes downstream of the interleukin (IL)-17 signaling pathway.A PPI network comprising 177 nodes and 318 edges was obtained. The GO analysis of the overlapping genes showed enrichment in response to lipopolysaccharide and oxidative process. For the KEGG analysis, the AGE-RAGE signaling pathway and inflammation-related pathways, such as the IL-17 and tumor necrosis factor (TNF) signaling pathways, were enriched. The in vitro experiments showed that HQ promoted the apoptosis of CRC cells by inhibiting the expression of the CCL2, CXCL8, CXCL10, and PTGS2 genes.This study systematically revealed the multitarget mechanism of HQ in CRC through a network pharmacology approach. We verified that HQ promotes CRC cell death via the IL-17 signaling pathway. This finding provides indications for further mechanistic studies and the development of HQ as a potential treatment for CRC patients.
To investigate the protective effects on allografts and the possible mechanism of adeno-associated heme-oxygenase-1 (AdHO-1) gene therapy against chronic rejection injury.Ex vivo AdHO-1 gene therapy was performed in vascular and renal transplantation models. The structure and function, the expression of therapeutic genes and proteins, and the immune modulation were analyzed.AdHO-1 gene therapy protected renal transplant against chronic rejection, but the effect was not as remarkable as that in vascular transplant. The transfected empty vehicle aggravated chronic rejection damage in renal transplantation. AdHO-1 decreased the infiltration of macrophages and CD4(+) T cells.AdHO-1 gene therapy can lessen damage of chronic rejection in allografts. It plays roles by protecting transplants, down-regulating immune response and inducing immune deviation.
Colorectal cancer (CRC) is the third most common tumor worldwide. Aberrant N6-methyladenosine (m6A) modification can influence the progress of the CRC. Additionally, long noncoding RNA (lncRNA) plays a critical role in CRC and has a close relationship with m6A modification. However, the prognostic potential of m6A-related lncRNAs in CRC patients still remains to be clarified.We use "limma" R package, "glmnet" R package, and "survival" R package to screen m6A-related-lncRNAs with prognostic potential. Then, we comprehensively analysed and integrated the related lncRNAs in different TNM stages from TCGA database using the LASSO Cox regression. Meanwhile, the relationship between functional enrichment of m6A-related lncRNAs and immune microenvironment in CRC was also investigated using the TCGA database. A prognostic model was constructed and validated to determine the association between m6A-related lncRNAs in different TNM stages and the prognosis of CRC.We demonstrated that three related m6A lncRNAs in different TNM stages were associated with the prognosis of CRC patients. Patients from the TCGA database were classified into the low-risk and the high-risk groups based on the expression of these lncRNAs. The patients in the low-risk group had longer overall survival than the patients in the high-risk group (P < 0.001). We further constructed and validated a prognostic nomogram based on these genes with a C-index of 0.80. The receiver operating characteristic curves confirmed the predictive capacity of the model. Meanwhile, we also found that the low-risk group has the correlation with the dendritic cell (DC). Finally, we discovered the relationship between the m6A regulators and the three lncRNAs.The prognostic model based on three m6A-related lncRNAs exhibits superior predictive performance, providing a novel prognostic model for the clinical evaluation of CRC patients.
Immunotherapy of malignant tumor is a verified and crucial anti-tumor strategy to help patients with cancer for prolonging prognostic survival. It is a novel anticancer tactics that activates the immune system to discern and damage cancer cells, thereby prevent them from proliferating. However, immunotherapy still faces many challenges in view of clinical efficacy and safety issues. Various nanomaterials, especially gold nanoparticles (AuNPs), have been developed not only for anticancer treatment but also for delivering antitumor drugs or combining other treatment strategies. Recently, some studies have focused on AuNPs for enhancing cancer immunotherapy. In this review, we summarized how AuNPs applicated as immune agents, drug carriers or combinations with other immunotherapies for anticancer treatment. AuNPs can not only act as immune regulators but also deliver immune drugs for cancer. Therefore, AuNPs are candidates for enhancing the efficiency and safety of cancer immunotherapy.
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