Background/Aims: Gastric neuroendocrine tumors (G-NETs) are uncommon neoplasms that can present with or without clinical symptoms. In this study, we evaluated the incidence, prognosis, and temporal trends of G-NETs. Methods: We analyzed all cases of G-NETs registered in the Surveillance, Epidemiology, and End Results (SEER) database from 1973 to 2014. Incidence was estimated by age and joinpoint analyses. Survival rates were calculated and survival trends over time were evaluated. Results: A total of 3740 eligible patients were enrolled in the study. G-NETs incidence increased from 0.31 per 1 000 000 patients in 1975 to 4.85 in 2014, with an annual percentage changes (APCs) of 8.9% (95% confidence interval [CI] = 7.7% to 10.21%, P < 0.001, t test (29) from 1975 to 2001 and 3.6% from 2002 to 2014 (95% CI= 2.3% to 4.9%, P < 0.001). For cases diagnosed between 1973 and 1982, five-year survival was 62.8% ± 7.0% (Standard error, SE) and increased to 86.7% ± 0.7% for cases diagnosed between 2003 and 2012 (P < 0.001). Years of diagnosis, gender, age at diagnosis, marital status, grade, tumor size, tumor stage, and surgery performed or not were the strongest predictors of worse survival in both univariate and multivariate analysis (P<0.05). Conclusion: G-NETs are uncommon neoplasms but the incidence is growing. Survival has improved in the past decades. Years of diagnosis, gender, age at diagnosis, marital status, grade, tumor size, tumor stage, and surgery status predict survival in patients with G-NETs.

While many anti-cancer modalities have shown potent efficacy in clinical practices, cancer prevention, timely detection, and effective treatment are still challenging. As a newly recognized iron-dependent cell death mechanism characterized by excessive generation of lipid peroxidation, ferroptosis is regarded as a potent weapon in clearing cancer cells. The cystine/glutamate antiporter solute carrier family 7 member 11 (SLC7A11) is the core target for ferroptosis regulation, the overexpression of which dictates downregulated sensitivity to ferroptosis in cancer cells. Hence, we elaborated the pan-cancer level bioinformatic study and systematically elucidated the role of intra-tumoral expression of SLC7A11 in the survival of cancer patients and potential immunotherapeutic response. Specifically, 25/27 (92.6%) cancers were featured with upregulated SLC7A11 expression, where SLC7A11 overexpression is a risk factor for worse overall survival in 8 cancers. We also validated SLC7A11 expression in multiple pancreatic cancer cell lines in vitro and found that it was upregulated in most pancreatic cancer cell lines (p &lt; 0.05). Single-cell sequencing method revealed the SLC7A11 was majorly expressed in cancer cells and mononuclear cells. To further explore the function of SLC7A11 in cancer progression, we analyzed the influence on cell proliferation after the knockdown or knockout of SLC7A11 by either CRISPR or RNAi methods. Besides, the association between SLC7A11 and drug resistance was characterized using bioinformatic approaches as well. We also analyzed the association between the expression of SLC7A11 in multi-omics level and the intra-tumoral infiltration of immune cells based on cell annotation algorithms. Moreover, the relationship between SLC7A11 and the expression of MHC, immune stimulators, immune inhibitors as well as the response to immunotherapy was investigated. In addition, the SLC7A11 expression in colon adenocarcinoma, uterine corpus endometrial carcinoma, and stomach adenocarcinoma (STAD) is also positively associated with microsatellite instability and that in head and neck squamous cell carcinoma, STAD, and prostate adenocarcinoma is positively associated with neoantigen level, which further revealed the potential relationship between SLC7A11 and immunotherapeutic response.

Background: Understanding the molecular mechanism of long non-coding RNAs (lncRNAs) in carcinogenesis is conducive for providing potential target for cancers. The role of FLVCR1-AS1 in breast cancer (BC) has not been probed yet. Materials and methods: qRT-PCR and western blot assays were used to estimate relevant expressions of mRNAs and proteins. CCK8, MTT and EdU were implemented to assess cell proliferation ability. TUNEL was performed to investigate cell apoptosis, whereas transwell assay was performed to test cell migration and invasion capacities. TOP/ FOP Flash assay was conducted to determine the activity of Wnt/β-catenin pathway. Luciferase reporter, RNA pull down and RIP assays were performed to verify interaction between genes. Results: FLVCR1-AS1 was abnormally up-regulated in BC cells. Silencing FLVCR1-AS1 inhibited cell proliferation, migration, invasion, yet accelerating apoptosis. Inhibition of miR-381-3p reversed the tumor restraining impacts of FLVCR1-AS1 depletion on BC progression. Additionally, CTNNB1 was recognized to be targeted by miR-381-3p. FLVCR1-AS1 aggravated BC malignant progression via up-regulation CTNNB1 through sponging miR-381-3p. Conclusion: FLVCR1-AS1 regulates BC malignant behavior via sequestering miR-381-3p and then freeing CTNNB1, implying a promising target for BC therapy.