Identification and Validation of a Novel Necroptosis-Related Long Noncoding RNA Prognostic Signature for Lung Adenocarcinoma.

Background: Several cancers, including lung adenocarcinoma (LUAD), are caused by genes related to necroptosis. However, it is still unknown how necroptosis-related long noncoding RNAs (lncRNAs) may be involved in LUAD. In order to predict the prognosis of LUAD patients and personalize immunotherapy, this study set out to construct a necroptosis-related lncRNA prognostic signature (NLPS). Methods: The Cancer Genome Atlas (TCGA) database was used to download the LUAD transcriptome data and the associated clinical data. lncRNAs associated with necroptosis were screened using coexpression analysis. An NLPS was built using univariate and least absolute shrinkage and selection operator (LASSO) Cox regression analyses. The Gene Expression Omnibus (GEO) database's GSE30219 was used to validate the NLPS. The prognostic value of the risk score was assessed using Kaplan-Meier survival, receiver operating characteristic (ROC) Cox regression, multivariate Cox regression, and nomogram analyses. Then, we looked into the differences between the low- and high-risk groups in the tumor immune microenvironment, immunotherapy response, and half-maximal inhibitory concentration (IC50). Results: The 14 lncRNAs in a novel NLPS were created. With further validation in the GSE30219 dataset, the risk score according to the NLPS was an independent prognostic indicator for LUAD patients. Patients with better overall survival (OS) in the low-risk group, who were characterized by increased immune cell infiltration, tumor mutational burden (TMB), and immunophenoscore (IPS), may have hot tumors and higher immunotherapy response rates. In addition, the risk score was also closely linked to sensitivity to various anticancer medications. Conclusions: We constructed a novel NLPS that could predict OS and sensitivity to immunotherapy in LUAD patients.

A comprehensive analysis and validation of cuproptosis-associated genes across cancers: Overall survival, the tumor microenvironment, stemness scores, and drug sensitivity.

Background: Cuproptosis is a novel type of cell death induced by copper. Cuproptosis-associated genes play a crucial part in oncogenesis and the growth and metastasis of tumors. However, the correlations among cuproptosis-associated genes, overall survival, the tumor microenvironment, and drug sensitivity remain unclear. Therefore, we performed an analysis of cuproptosis-associated genes across cancers. Methods: We downloaded RNA sequence expression data, clinical and survival data, stemness score data, and immune subtype data of cuproptosis-associated genes from the UCSC Xena. Next, we conducted differential analysis, expression analysis and correlation analysis across cancers with various R packages. Moreover, survival analysis and Cox hazard analysis were conducted to investigate the relationships between cuproptosis-associated genes and survival outcomes in various cancer types. Finally, we also analyzed the relationship among the levels of cuproptosis-associated genes across cancers, immune types, the tumor microenvironment, stemness scores, and drug sensitivity. Expression validation of cuproptosis-associated genes in renal cancer and normal tissues by immunohistochemical staining. Results: We found that 10 cuproptosis-associated genes (FDX1, LIAS, LIPT1, DLD, DLAT, PDHA1, PDHB, MTF1, GLS, and CDKN2A) were differently expressed in 18 tumors and normal tissues. Survival outcomes showed that cuproptosis-associated genes had prognostic value in various cancer types. Moreover, we identified that cuproptosis-associated genes had different levels in six immune subtypes. The study also indicated that the levels of most cuproptosis-associated genes were positively correlated with the RNAss and DNAss. FDX1, LIAS, LIPT1, DLD, DLAT, PDHA1, and PDHB were negatively correlated with immune scores and ESTIMATE scores. In addition, we identified the top 16 drugs strongly sensitivity to cuproptosis-associated genes according to the correlation coefficient. Finally, we also found that cuproptosis-associated genes were significantly correlated with immune subtype, clinical features, the tumor microenvironment, and drug sensitivity in Kidney renal clear cell carcinoma. And the results of immunohistochemical staining analysis was very consistent with the previous analysis. Conclusion: We performed an overall analysis to uncover the roles of cuproptosis-associated genes in differential expression, survival outcomes, immune subtypes, the tumor microenvironment, stemness scores, and cancer drug sensitivity across cancers.