A prognostic signature of pyroptosis-related lncRNAs verified in gastric cancer samples to predict the immunotherapy and chemotherapy drug sensitivity

Abstract

Background: Pyroptosis is a recently identified mode of programmed inflammatory cell death that has remarkable implications for cancer development. lncRNAs can be involved in cellular regulation through various pathways and play a critical role in gastric cancer (GC). However, pyroptosis -related lncRNAs (PRlncRNAs) have been rarely studied in GC.Methods: Pyroptosis-related gene were abstracted from the literature and GSEA Molecular Signatures data resource. PRlncRNAs were obtained using co-expression analysis. LASSO Cox regression assessment was employed to build a risk model. Kaplan-Meier (KM), univariate along with multivariate Cox regression analysis were adopted to verify the predictive efficiency of the risk model in terms of prognosis. qRT-PCR was adopted to validate the expression of PRlncRNAs in GC tissues. In addition, immune cell infiltration assessment and ESTIMATE score evaluation were adopted for assessing the relationship of the risk model with the tumor immune microenvironment (TME). Finally, immune checkpoint gene association analysis and chemotherapy drug sensitivity analysis were implemented to assess the worthiness of our risk model in immunotherapy and chemotherapy of GC.Results: We identified 3 key PRlncRNAs (PVT1, CYMP-AS1 and AC017076.1) and testified the difference of their expression levels in GC tumor tissues and neighboring non-malignant tissues (p < 0.05). PRlncRNAs risk model was able to successfully estimate the prognosis of GC patients, and lower rate of survival was seen in the high-GC risk group relative to the low-GC risk group (p < 0.001). Other digestive system tumors such as pancreatic cancer further validated our risk model. There was a dramatic difference in TMB level between high-GC and low-GC risk groups (p < 0.001). Immune cell infiltration analysis and ESTIMATE score evaluation demonstrated that the risk model can be adopted as an indicator of TME status. Besides, the expressions of immunodetection site genes in different risk groups were remarkably different (CTLA-4 (r = −0.14, p = 0.010), VISTA (r = 0.15, p = 0.005), and B7-H3 (r = 0.14, p = 0.009)). PRlncRNAs risk model was able to effectively establish a connection with the sensitivity of chemotherapeutic agents.Conclusion: The 3 PRlncRNAs identified in this study could be utilized to predict disease outcome in GC patients. It may also be a potential therapeutic target in GC therapy, including immunotherapy and chemotherapy.

Long Non-Coding RNAs in Drug Resistance of Gastric Cancer: Complex Mechanisms and Potential Clinical Applications

“…In this review, a total of 17 articles ( Table 3 ) used the differential expression of different functionally related lncRNAs to construct algorithms, so as to provide a basis for guiding clinical prognosis and predicting therapeutic effects. Four articles [ 191 , 192 , 193 , 194 ] used drug-resistant tissues or cells (PR, MDR, and DCSR) for differential lncRNA screening to construct a model. Four articles [ 193 , 194 , 195 , 196 ] constructed prediction models based on pyroptosis-related lncRNAs (PRlncRNAs).…”

“…Four articles [ 191 , 192 , 193 , 194 ] used drug-resistant tissues or cells (PR, MDR, and DCSR) for differential lncRNA screening to construct a model. Four articles [ 193 , 194 , 195 , 196 ] constructed prediction models based on pyroptosis-related lncRNAs (PRlncRNAs). These research studies all conducted the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm to construct the PRlncRNA model.…”

Astragaloside IV, as a potential anticancer agent

“…B7-H3, a member of B7 family, plays a key role in carcinogenesis and tumor progression (Flem-Karlsen et al, 2019). Up-regulation of B7-H3 exists in a variety of cancers, such as lung cancer, colorectal cancer, pancreatic cancer (Carvajal-Hausdorf et al, 2019;Ma et al, 2020;Wang et al, 2022b). The mRNA and protein levels of B7-H3 in non-small-cell lung cancer cells treated with AS-IV and cisplatin…”

M6A methylation of FKFB3 reduced pyroptosis of gastric cancer by NLRP3

“…Meanwhile, targeting cancer cells to induce cell pyroptosis can effectively kill cancer cells. The relationship between cell death and cancer is very complex [11,12]. The impact of pyroptosis on cancer is complex, as it can both inhibit tumor growth and promote tumor development [10].…”