Comprehensive analysis of cuproptosis-related lncRNAs in immune infiltration and prognosis in hepatocellular carcinoma

Abstract

Background Being among the most common malignancies worldwide, hepatocellular carcinoma (HCC) accounting for the third cause of cancer mortality. The regulation of cell death is the most crucial step in tumor progression and has become a crucial target for nearly all therapeutic options. Cuproptosis, a copper-induced cell death, was recently reported in Science. However, its primary function in carcinogenesis is still unclear. Methods Cuproptosis-related lncRNAs significantly associated with overall survival (OS) were screened by stepwise univariate Cox regression. The signature of cuproptosis-related lncRNAs for HCC prognosis was constructed by the LASSO algorithm and multivariate Cox regression. Further Kaplan–Meier analysis, proportional hazards model, and ROC analysis were performed. Functional annotation was performed using gene set enrichment analysis (GSEA). The relationship between prognostic cuproptosis-related lncRNAs and HCC prognosis was further explored by GEPIA(http://gepia.cancer-pku.cn/) online analysis tool. Finally, we used the ESTIMATE and XCELL algorithms to estimate stromal and immune cells in tumor tissue and cast each sample to infer the underlying mechanism of cuproptosis-related lncRNAs in the tumor immune microenvironment (TIME) of HCC patients. Results Four cuproptosis-related lncRNAs were used to construct a prognostic lncRNA signature, which was an independent factor in predicting OS in HCC patients. Kaplan–Meier curves showed significant differences in survival rates between risk subgroups (p = 0.002). At the same time, we found that the expression levels of most immune checkpoint genes increased with increasing risk scores. Tumorigenesis and immunological-related pathways were primarily enhanced in the high-risk group, as determined by GSEA. The results of drug sensitivity analysis showed that compared with patients in the high-risk group, the IC50 values of erlotinib and lapatinib were lower in patients in the low-risk group, while the opposite was true for sunitinib, paclitaxel, gemcitabine, and imatinib. We also found that elevated AL133243.2 expression was significantly associated with worse OS and disease-free survival (DFS), more advanced T stage and higher tumor grade, and reduced immune cell infiltration, suggesting that HCC patients with low AL133243.2 expression in tumor tissues may have a better response to immunotherapy. Conclusion Collectively, the cuproptosis-associated lncRNA signature can serve as an independent predictor to guide individual treatment strategies. Furthermore, AL133243.2 is a promising marker for predicting immunotherapy response in HCC patients. This data may facilitate further exploration of more effective immunotherapy strategies for HCC.

Machine learning-based disulfidptosis-related lncRNA signature predicts prognosis, immune infiltration and drug sensitivity in hepatocellular carcinoma

“…The high expression of SLC7A11 in cancer cells results in excessive uptake of cystine into the cell, the reduction process of which consumes large amounts of NADPH (glucose metabolite) and induces cell-specific death by inhibiting glucose transporter. lncRNAs can play a regulatory role in programmed cell death through gene transcription and post-transcriptional modification, and act as potential therapeutic targets and biomarkers for the prediction and diagnosis of cancer patients, e.g., ferroptosis-related lncRNAs signature 12 , and cuproptosis-related lncRNAs signature 13 in the prognosis of HCC. However, it is not yet clear the value and significance of DRLs in the prediction of prognosis of HCC patients.…”

Machine Learning-Based Disulfidptosis-Related lncRNA Signature Predicts Prognosis, Immune Infiltration and Drug Sensitivity in Hepatocellular Carcinoma

“…The high expression of SLC7A11 in cancer cells results in excessive uptake of cystine into the cell, the reduction process of which consumes large amounts of NADPH (glucose metabolite) and induces cellspeci c death by inhibiting glucose transporter. lncRNAs can play a regulatory role in programmed cell death through gene transcription and post-transcriptional modi cation, and act as potential therapeutic targets and biomarkers for the prediction and diagnosis of cancer patients, e.g., ferroptosis-related lncRNAs signature [9], and cuproptosis-related lncRNAs signature [10] in the prognosis of HCC. However, it…”

Identification of differentially expressed mRNA/lncRNA modules in acutely regorafenib-treated sorafenib-resistant Huh7 hepatocellular carcinoma cells

“…Notable lncRNAs of the green module (increased in SR, then decreased under regorafenib) include ARHGEF2-AS2, a survival predictor in clear cell renal cell carcinoma (ccRCC) [43], and AC007563.2, AC013451.1, LINC00607, and LINC01583, which are potentially involved in angiogenesis and cell adhesion [44][45][46][47]. Notable lncRNAs of the yellow module (decreased in SR, then increased after regorafenib) include the oncogenic molecules CHRM3-AS2 [48] and DLX6-AS1 [49] as well as AL137127.1, AC020978.3 and LINC01242, which are thought to promote chromatin remodeling in HCC [50,51]. The red module (increased in SR, further increased with regorafenib) did not contain any DElncRNAs, and the DEmRNAs in this module have been reported to act as tumor suppressors [52][53][54].…”