A novel prognostic signature based on cuproptosis-related lncRNA mining in colorectal cancer

Abstract

Background: Colorectal cancer (CRC) is a common malignant tumor that affects the large bowel or the rectum. Cuproptosis, recently discovered programmed cell death process, may play an important role in CRC tumorigenesis. Long non-coding RNAs (lncRNAs) can alter the proliferation of colorectal cancer cells through the control and activation of gene expression. To date, cuproptosis-related lncRNAs, have not been investigated as potential predictive biomarkers in colorectal cancer.Methods: The mRNA and lncRNA expression data of colorectal cancer were gathered from The Tumor Genome Atlas (TCGA) database, and Pearson correlation analysis and univariate Cox regression analysis were used to identify the lncRNAs with differential prognosis. Colorectal cancer was classified using consistent clustering, and the clinical significance of different types, tumor heterogeneity, and immune microenvironment differences was investigated. The differential lncRNAs were further screened using LASSO regression to develop a risk scoring model, which was then paired with clinicopathological variables to create a nomogram. Finally, the copy number changes in the high-risk and low-risk groups were compared.Results: Two clusters were formed based on the 28 prognostic cuproptosis-related lncRNAs, and the prognosis of cluster 2 was found to be significantly lower than that of cluster 1. Cluster 1 showed increased immune cell infiltration and immunological score, as well as strong enrichment of immune checkpoint genes. Next, LASSO regression was used to select 11 distinctive lncRNAs, and a risk score model was constructed using the training set to distinguish between high and low-risk groups. Patients in the high-risk group had a lower survival rate than those in the low-risk group, and both the test set and the total set produced consistent results. The AUC value of the ROC curve revealed the scoring model’s efficacy in predicting long-term OS in patients. Moreover, the model could be used as an independent predictor when combined with a multivariate analysis of clinicopathological features, and our nomogram could be used intuitively to predict prognosis.Conclusion: Collectively, we developed a risk model using 11 differential lncRNAs and demonstrated that the model has predictive value as well as clinical and therapeutic implications for predicting prognosis in CRC patients.

Cuproptosis: mechanisms and links with cancers

“…In addition, Enamelin(ENAM) and WD repeat domain 72(WDR72) were considered to be both associated with enamel construction in previous studies [ 186 ] and as risk or protective factors in studies on KIRC, respectively [ 149 , 150 ]. MKLN1-AS and AL031985.3 were both considered risk factors for patients with hepatocellular carcinoma [ 136 , 163 ], FOXD2-AS1 and LINC02154 were both considered risk factors for KIRC patients [ 175 – 177 ], AL513550.1 was suggested as a risk factor for CRC by different investigators [ 121 , 172 ], and AL132800.1 was thought to be a risk factor for HNSCC [ 178 , 179 ]. C6orf99 was regarded as a risk factor for patients with OSCC and HNSCC, two tumors with similar pathological types [ 152 , 173 ].…”

“…C6orf99 was regarded as a risk factor for patients with OSCC and HNSCC, two tumors with similar pathological types [ 152 , 173 ]. In contrast, upregulation of AC090587.1 and AC012313 was identified to be associated with a better prognosis in HNSCC patients [ 178 , 179 ], while AC073896.3 was used as a protective factor in the prognostic analysis of CRC patients [ 121 , 172 ]. Certain lncRNAs were also hinted that may serve as protective or risk factors in different prognostic signatures of the same or different tumors, respectively.…”

“…Certain lncRNAs were also hinted that may serve as protective or risk factors in different prognostic signatures of the same or different tumors, respectively. AC026979.4 was considered as a risk or protective factor among the different prognostic signatures of CRC patients [ 121 , 172 ], and upregulation of LINC01150 was associated with better or worse prognosis in the prognostic analyses of STAD patients and CM patients [ 168 , 181 ]. These possible relationships need to be verified by deeper mechanistic studies and multi-omics level analysis.…”

Cuproptosis-related lncRNA signature for prognostic prediction in patients with acute myeloid leukemia

“…Several recent studies confirmed that N6-methyadenosine-related lncRNAs predicted AML prognosis and the immune landscape [20][21][22]. Moreover, it is worth mentioning that cuproptosis-related lncRNA signature also showed promising prognosis prediction potential in carcinomas, including hepatocellular carcinoma [23], lung adenocarcinoma [24], colon adenocarcinoma [25], and colorectal cancer [26]. However, whether cuproptosis-related lncRNA signature could be utilized for the prediction of AML prognosis and immune response is largely unknown.…”

Cuproptosis-related lncRNA signature for prognostic prediction in patients with acute myeloid leukemia

“…Several recent studies con rmed that N6methyadenosine-related lncRNAs could predict AML prognosis and the immune landscape [16][17][18]. It is worth mentioning that cuproptosis-related lncRNA signature also showed promising prognosis prediction in kinds of carcinomas, including hepatocellular carcinoma [19], lung adenocarcinoma [20], colon adenocarcinoma [21] and colorectal cancer [22]. Therefore, considering the important role of copper in human bodies, we speculated that cuproptosis-related lncRNAs might also be utilized for the prediction of AML prognosis and immune response.…”