Discussion
RS, death, non-small cell lung cancers, RCD, Alzheimer's disease mice, tumour
NON-SMALL CELL LUNG CANCER, INFILTRATION, DISEASE, OROPHARYNGEAL CANCER, CERVICAL CANCER, TUMOUR, REGRESSION, OXIDATIVE STRESS, INFILTRATED
Regulatory cell death (RCD) was discovered as a type of cell death mediated by activation of one or more signalling pathways and is critical for normal cell growth and the immune response, and evasion of RCD is one of the key hallmarks of cancersAs high-throughput sequencing technology becomes widely available, a growing number of research have been carried out to predict the prognosis of cervical cancer patients by the alteration of a single lncRNA or combined expression of several lncRNAs in body fluidsIn this research, we selected 703 cuproptosis-associated lncRNAs from TCGA-CESE transcriptomic data by Pearson correlation analysis based on 19 cuproptosis-associated genes. Then, 18 cuproptosis-related lncRNAs associated with CC prognosis were identified by univariate Cox regression, and after LASSO and multivariate Cox regression, a risk prediction model containing AL441992.1, SOX21-AS1, AC011468.3, AC012306.2, FZD4-DT, AP001922.5, RUSC1-AS1, and AP001453.2 was constructed. There have been several previous reports on the establishment of cuproptosis-related lncRNA models for predicting the prognosis of cervical cancerMain characteristics of the previous related studies.According to previous studies, the lncRNA SOX21 antisense RNA 1 (SOX21-AS1) can alleviate oxidative stress and inhibit neuronal apoptosis in Alzheimer's disease mice and is associated with disease developmentTo assess the prognostic value of our 8-CRLs signature for predicting OS and PFS in CC patients as well as its effectiveness in assessing response of CC patients to immunotherapy with ICIs, CC patients were randomly allocated to training and test cohorts at a 1:1 ratio. Significantly shorter overall survival times were observed for CC patients in the high-risk group in the training, test and entire cohorts. These prognostic differences between two risk subgroups based on different clinical characteristics were clearly illustrated using Kaplan–Meier survival analysis, including age groups, G1-2/G3-4 stage groups, M0/M1 stage groups, and N0/N1 stage groups. According to ROC curves, the signature showed good prediction effectiveness in the training cohort, test cohort, and entire cohort. The AUC values of the model were greater than 0.7 at 1, 3, and 5 years. The remarkable capacity of our model to distinguish between high- and low-risk groups in all samples was clearly shown by PCA.Our prognostic signature was also linked to infiltration of immune cells in the TME and immune-related biomarkers to predict the clinical outcome of immunotherapy. We discovered that the risk subgroups have diverse tumour microenvironments, which may lead to differences in prognosis and response to immunotherapy. For samples with a high RS, the stromal score and immune score were lower, and the tumour purity was higher. Levels of M0 macrophages and activated mast cells were higher in the TME of high-RS samples. These aberrantly infiltrated immune cells may be associated with the advancement and poor prognosis of cervical cancer. It is undeniable that CD8ICIs immunotherapy consisting of anti-CTLA4 and anti-PD1 has been shown to be effective in non-small cell lung cancers and oropharyngeal cancer, and the feasibility of applying immunotherapy to cervical cancer is receiving increasing attention and researchHowever, we admit that our research has certain limitations. First, this was a retrospective study using data from the TCGA database. Therefore, some discrepancies may exist. Second, another limitation of this study was the reliance on a single cervical cancer cell line. We will subsequently include more samples and cell lines for validation when available. Third, the mechanism of function of cuproptosis-related lncRNAs requires further experimental demonstration, and the validity of the 8-CRLs signature established in this study needs additional confirmation in clinical trials with large samples.As mentioned above, the 8-CRLs signature was found to be efficient in independently predicting the prognosis of CC patients. This study will serve as a foundation for future research on the mechanism and clinical therapeutic effectiveness of cuproptosis-related lncRNAs in CC, but further experimental validation is still needed.