Prognosis and personalized treatment prediction in lung adenocarcinoma: An in silico and in vitro strategy adopting cuproptosis related lncRNA towards precision oncology

Abstract

Background: There is a rapid increase in lung adenocarcinomas (LUAD), and studies suggest associations between cuproptosis and the occurrence of various types of tumors. However, it remains unclear whether cuproptosis plays a role in LUAD prognosis.Methods: Dataset of the TCGA-LUAD was treated as training cohort, while validation cohort consisted of the merged datasets of the GSE29013, GSE30219, GSE31210, GSE37745, and GSE50081. Ten studied cuproptosis-related genes (CRG) were used to generated CRG clusters and CRG cluster-related differential expressed gene (CRG-DEG) clusters. The differently expressed lncRNA that with prognosis ability between the CRG-DEG clusters were put into a LASSO regression for cuproptosis-related lncRNA signature (CRLncSig). Kaplan–Meier estimator, Cox model, receiver operating characteristic (ROC), time-dependent AUC (tAUC), principal component analysis (PCA), and nomogram predictor were further deployed to confirm the model’s accuracy. We examined the model’s connections with other forms of regulated cell death, including apoptosis, necroptosis, pyroptosis, and ferroptosis. The immunotherapy ability of the signature was demonstrated by applying eight mainstream immunoinformatic algorithms, TMB, TIDE, and immune checkpoints. We evaluated the potential drugs for high risk CRLncSig LUADs. Real-time PCR in human LUAD tissues were performed to verify the CRLncSig expression pattern, and the signature’s pan-cancer’s ability was also assessed.Results: A nine-lncRNA signature, CRLncSig, was built and demonstrated owning prognostic power by applied to the validation cohort. Each of the signature genes was confirmed differentially expressed in the real world by real-time PCR. The CRLncSig correlated with 2,469/3,681 (67.07%) apoptosis-related genes, 13/20 (65.00%) necroptosis-related genes, 35/50 (70.00%) pyroptosis-related genes, and 238/380 (62.63%) ferroptosis-related genes. Immunotherapy analysis suggested that CRLncSig correlated with immune status, and checkpoints, KIR2DL3, IL10, IL2, CD40LG, SELP, BTLA, and CD28, were linked closely to our signature and were potentially suitable for LUAD immunotherapy targets. For those high-risk patients, we found three agents, gemcitabine, daunorubicin, and nobiletin. Finally, we found some of the CRLncSig lncRNAs potentially play a vital role in some types of cancer and need more attention in further studies.Conclusion: The results of this study suggest our cuproptosis-related CRLncSig can help to determine the outcome of LUAD and the effectiveness of immunotherapy, as well as help to better select targets and therapeutic agents.

Development of m6A/m5C/m1A regulated lncRNA signature for prognostic prediction, personalized immune intervention and drug selection in LUAD

“…The situation of the target gene in the real world can be described by laboratory data obtained from human samples. The expression level of each mRLncSig lncRNA was investigated by collecting nine pairs of LUAD and adjacent tissues from the clinic 70 . All patients included in this study did not receive any relevant treatment before collecting samples.…”

“…In both datasets, the drug sensitivity was determined by the area under the dose–response curve (AUC), with lower values indicating greater sensitivity. Our study involves the analysis of drug response data from CTRP and PRISM to identify feasible drug candidates from the high‐scoring group 70 . To do this, we compared drug responses between patients with the highest and lowest decile risk scores and used a threshold of log2FC > 0.1 to screen for drugs with lower AUC in high‐scoring patients 71 .…”

“…72 Detection of genes between normal and tumour samples was conducted utilizing Student's t-test, with statistical significance established for adjusted p-values below 0.05. 72 For our pan-cancer analysis, 70 we opted for the TCGA pancancer data that we obtained from the UCSC database (https:// xenab rowser. net/ ).…”

“…To gain insights into F I G U R E 1 Research design and analysis process. 70 the underlying mechanisms responsible for the divergence between the two mRG clusters, we delved deeper into the genes that were expressed differentially, ultimately identifying 256 mRG clusterrelated differentially expressed genes (mRG-DEGs) (Table S3).…”

Disulfidptosis-related lncRNA signatures in lung adenocarcinoma: Predicting prognosis and evaluating the tumor immune microenvironment

“…In addition to ferroptosis, cuproptosis isanother key point of RCD research. Furthermore, several cuproptosis-related lncRNA-based signatures have been developed for the prognosis prediction of LUAD patients[34,35].Disul dptosis, differs from the previous RCD such as ferroptosis and cuproptosis, is a novel kind of RCD reported recently opening up new possibilities for cancer treatment. Liu's research revealed that cancer cells overexpressing SLC7A11 undergo a unique form of cell death when exposed to glucose deprivation, distinct from recognized cell death subtypes.…”