Discussion
colorectal cancer, T stage, tumour, CRPC
NON-SMALL CELL LUNG CANCER, OVARIAN CANCER, COLORECTAL CANCER, INFILTRATION, PROLIFERATION, MICROSATELLITE INSTABILITY, TUMOUR
LncRNA has mRNA-like transcripts which are not capable of encoding proteins or peptides. Its plays an essential role in the regulation of gene expression at the transcriptional, translational, and post-translational levels [In our study, Pearson's correlation and differential expression analysis was applied to identify differentially expressed cuproptosis-related lncRNAs. The novel lncRNA signature which consist of AC005790.1, AC011472.4, AC099791.2, AC144450.1, LIPE-AS1, and STPG3-AS1 was further developed via the combined algorithm [Lasso and stepwise Cox (direction = both)]. This model can not only effectively avoid the issue of multicollinearity but also precisely screen the key variables. Both the K-M survival curve and the ROC curve presented that the consensus lncRNA signature could stratify the risk of PCa patients with high precision and stability performance in training, validation, and entire cohorts of TCGA. Moreover, the cuproptosis-related lncRNA signature was also closely associated with the common clinical feature, such as T stage, N stage, and Gleason score. To better understand the mechanism underlying the cuproptosis-related lncRNA signature, it is necessary to analyse the role of each gene in cuproptosis. Chu et al. founded that the Toll-like receptors related prognostic gene signature involving AC011472.4 is an independent risk indicator in colorectal cancer [To further explore the potential mechanism of the cuproptosis-related lncRNA signature in PCa, these functional analyzes, including functional enrichment, immune, gene mutation, tumour mutational burden, microsatellite instability, and drug sensitivity analysis, were conducted. The results of the functional enrichment analysis found that the differentially expressed coding RNA genes between both groups were mainly enriched in the transport of ion and small molecules, which further confirmed the molecular characteristics of the cuproptosis-related lncRNA signature. In GSEA enrichment analyses, the high-risk group tends to enrich in cellular functions such as cell cycle and proliferation, while the low-risk group in biological processes involving energy metabolism. In addition, 28 immune cell infiltration and immune-related function were also analysed via ssGSEA algorithms to elucidate the relationship between this risk signature and the immune microenvironment of tumour. The content of activated, memory, and immature B cell were elevated in the low-risk group. B cells, as vital components of the adaptive immune system, are commonly found in various tumour tissues, such as breast, cervical, and ovarian cancer, and non-small cell lung cancer [With the development of next-generation sequencing, germline and somatic genetic testing are considered to guide the clinical practice. Based on the identification of DNA repair gene defects, poly (ADP-ribose) polymerase (PARP) inhibitors were developed and utilized to control tumour. Currently, Olaparib was the first PARP inhibitor to show significant activity in metastatic CRPC with prior progression to standard therapy [Although this study develops the novel cuproptosis-related lncRNA signature, several limitations should be realized. Fistly, the prognosis signature cannot be validated by external validation cohorts, as other current datasets a lack for the lncRNA sequencing data and complete clinical information. Secondly, the latent mechanism underlying cuproptosis-related lncRNA along with its relationship with tumour immune microenvironment, gene mutation, TMB, MSI, and the drug sensitivity should be further validated in vivo and in vitro experiments.