Pyroptosis is an inflammatory form of programmed cell death triggered by caspase-1/4/5/11 that plays an important role in the occurrence and development of gastric cancer (GC). We investigated the prognostic value of pyroptosis-related genes in GC. The “LIMMA” R package and univariate Cox analysis were used to find pyroptosis-related genes with differential expression and prognostic value in the TCGA cohort and the identified genes were analyzed for GO enrichment and KEGG pathways. The selected genes were then included in a multivariate Cox proportional hazard regression analysis, and a ten genes prognostic model (BIRC2, CD274, IRGM, ANXA2, GBP5, TXNIP, POP1, GBP1, DHX9, and TLR2) was established. To evaluate the predictive value of the risk score on prognosis, patients were divided into high-risk and low-risk groups according to the median risk score, and survival analysis was carried out. Compared with the low-risk group, the OS of GC patients in the high-risk group was significantly worse. Additionally, these results were verified in the GSE84437 and GSE66229 datasets. Finally, through the combination of prognostic gene characteristics and clinicopathological features, a nomogram was established to predict individual survival probability. The results show that the genetic risk characteristics related to clinical features can be used as independent prognostic indicators for patients with GC. In summary, the pyroptosis-related risk signals proposed in this study can potentially predict the prognosis of patients with GC. In addition, we also found significant infiltration of dendritic cells, macrophages, and neutrophils in tissues of high-risk patients.

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Background and aimsStudies show that the long non-coding RNA, SBF2-AS1, plays a critical role in cancer progression, but the role of SBF2-AS1 in gastric cancer has not been reported. Therefore, this study aimed to elucidate the mechanism of SBF2-AS1 in gastric cancer (GC).MethodsA meta-analysis, based on the gene expression omnibus database and TCGA dataset was performed to explore the prognostic value of SBF2-AS1 in GC. RT-PCR was also conducted to investigate the clinicopathologic value of SBF2-AS1 in GC. The effect of SBF2-AS1 in GC cell lines was conducted by gain or loss-of-function assays, and the SBF2-AS1 target gene was confirmed using a luciferase reporter assay and bioinformatics.ResultsSBF2-AS1 was overexpressed in GC tissues and cell lines, and SBF2-AS1 overexpression indicated poor overall survival and could serve as an independent prognostic factor. Moreover, knockdown of SBF2-AS1 inhibited cell growth, invasion, and metastasis, promoted apoptosis, and caused cell cycle arrest. Luciferase reporter and gain- or loss-of-function assays indicated that SBF2-AS1 acted as a competing endogenous (ceRNA) for microRNA (miR)-302b-3p, which blocked the inhibitory effect of miR-302b-3p on the E2F transcription factor 3 (E2F3).ConclusionSBF2-AS1 could be a potential diagnostic and prognostic biomarker in GC, and SBF2-AS1 accelerates tumor progression via the miR-302b-3p/E2F3 axis.

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C, et al. The long non-coding RNA SBF2-AS1 exerts oncogenic functions in gastric cancer by targeting the miR-302b-3p/E2F transcription factor 3 axis.