Hsa_circ_0001479 accelerates tumorigenesis of gastric cancer and mediates immune escape.

Gastric cancer (GC) is a common fatal malignant tumor of the digestive tract, particularly in Asia. Circular RNA (circRNA) has been proved to regulate malignancy progression and immunotherapeutic efficacy in multiple tumors, including GC. Notably, the function of circRNAs in GC has not been completely revealed. Therefore, exploration of more GC related circRNAs may provide potential strategies for GC treatment. In the study, it was observed that hsa_circ_0001479 exhibited a high level of expression in GC and was subsequently found to be associated with the depth of invasion, lymph node metastasis, and TNM stage. Functionally, the overexpression of hsa_circ_0001479 was found to enhance the proliferation and migration of GC cells, as evidenced by various experiments such as CCK-8, EdU, colony forming and transwell. Dual-luciferase reporter assay verified that hsa_circ_0001479 upregulated DEK expression by sponge targeting miR-133a-5p. Further investigations indicated DEK affected the entry of ß-catenin into the nucleus by activating Wnt/ß-catenin signaling pathway to promote accumulation of downstream c-Myc. As a transcription factor, c-Myc combined with the promoter of hsa_circ_0001479 parent gene to stimulate hsa_circ_0001479 generation. Besides, hsa_circ_0001479 inhibited theinfiltration with CD8+T cells in GC and associated with immune checkpoints. In summary, hsa_circ_0001479 accelerated the development and metastasis of GC and mediates immune escape of CD8+T cells. Targeting it may provide a novel immunotherapy to better locally treat GC and reduce the incidence of metastases.

Overexpression of ferroptosis-related genes FSP1 and CISD1 is related to prognosis and tumor immune infiltration in gastric cancer

Purpose Gastric cancer (GC) is one of the highest incidence rate cancers worldwide and the search for new biomarkers remains urgent due to its relatively poor prognosis and limited treatment methods. Ferroptosis suppressor protein 1 (FSP1) and iron sulfur domain 1 (CISD1) promoted malignant tumor progression as ferroptosis suppressors in a variety of tumors, but their study in GC remains to be explored. Methods In our study, FSP1 and CISD1 expression were predicted through different databases and confirmed by qRT-PCR, immunohistochemistry and western blotting. Enrichment analyses were exploited to explore the potential functions of FSP1 and CISD1. Finally, their relationship with immune infiltration was determined by Tumor Immune Estimation Resource and ssGSEA algorithm. Results The expression of FSP1 and CISD1 was higher in GC tissues. Their strongly positive immunostaining was associated with increased tumor size, degree of differentiation, depth of invasion and lymph node metastasis in GC patients. Up-regulated FSP1 and CISD1 predicted poorer overall survival of patients with GC. Furthermore, FSP1 and CISD1 as ferroptosis inhibitors were predicted to be involved in GC immune cell infiltration. Conclusions Our study suggested that FSP1 and CISD1 acted as biomarkers of poor prognosis and promising immunotherapeutic targets for GC (AU)

Overexpression of ferroptosis-related genes FSP1 and CISD1 is related to prognosis and tumor immune infiltration in gastric cancer.

PURPOSE: Gastric cancer (GC) is one of the highest incidence rate cancers worldwide and the search for new biomarkers remains urgent due to its relatively poor prognosis and limited treatment methods. Ferroptosis suppressor protein 1 (FSP1) and iron sulfur domain 1 (CISD1) promoted malignant tumor progression as ferroptosis suppressors in a variety of tumors, but their study in GC remains to be explored. METHODS: In our study, FSP1 and CISD1 expression were predicted through different databases and confirmed by qRT-PCR, immunohistochemistry and western blotting. Enrichment analyses were exploited to explore the potential functions of FSP1 and CISD1. Finally, their relationship with immune infiltration was determined by Tumor Immune Estimation Resource and ssGSEA algorithm. RESULTS: The expression of FSP1 and CISD1 was higher in GC tissues. Their strongly positive immunostaining was associated with increased tumor size, degree of differentiation, depth of invasion and lymph node metastasis in GC patients. Up-regulated FSP1 and CISD1 predicted poorer overall survival of patients with GC. Furthermore, FSP1 and CISD1 as ferroptosis inhibitors were predicted to be involved in GC immune cell infiltration. CONCLUSIONS: Our study suggested that FSP1 and CISD1 acted as biomarkers of poor prognosis and promising immunotherapeutic targets for GC.

SLC6A3 as a potential circulating biomarker for gastric cancer detection and progression monitoring.

BACKGROUND: Gastric cancer is a malignant tumor originating from the gastric mucosal epithelium, with no obvious symptoms at the early stage. The dopamine transporter gene (SLC6A3) is involved in the metabolism of dopamine and catecholamine and is a potential gene for Parkinson's disease and alcoholism. But the role of SLC6A3 in gastric cancer is still unknown. The aim of our study is to investigate the potential diagnostic value of SLC6A3 on gastric cancer. METHODS: Quantitative real-time PCR (RT-qPCR) was used to detect the expression of SLC6A3 in clinical samples and cells. A total of 246 samples were enrolled in this study (26 pairs of tissue samples; Serum of 113 patients with gastric cancer, 51 polyps patients and 56 healthy controls). The diagnostic value of SLC6A3 was evaluated by the ROC curve and analyzed the changes of SLC6A3 expression before and after surgery. The prognostic value, interacting proteins and related pathways of SLC6A3 were evaluated by TCGA analysis in UALCAN database (http://ualcan.path.uab.edu/). RESULTS: The expression level of SLC6A3 in gastric cancer was significantly higher than that in controls. Further, the proportion under the ROC curve (AUC) for SLC6A3, CEA and CA19-9 was 0.818 (95 % confidence interval [CI]: 0.754 to 0.883, P < 0.001), and the expression level of SLC6A3 in the serum of patients with gastric cancer decreased significantly after surgery (P < 0.001). Bioinformatic enrichment analysis of SLC6A3 displayed the relevant metabolic pathways involved in its interacting proteins. CONCLUSION: SLC6A3 is involved in the occurrence and development of gastric cancer and can be used as a potential diagnostic indicator for gastric cancer.