Identification and integration analysis of a novel prognostic signature associated with cuproptosis-related ferroptosis genes and relevant lncRNA regulatory axis in lung adenocarcinoma

Abstract

Lung adenocarcinoma (LUAD) is a highly prevalent malignancy worldwide, and its clinical prognosis assessment and treatment is a major research direction. Both ferroptosis and cuproptosis are novel forms of cell death and are considered to be important factors involved in cancer progression. To further understand the correlation between the cuproptosis-related ferroptosis genes (CRFGs) and the prognosis of LUAD, we explore the molecular mechanisms related to the development of the disease. We constructed a prognostic signature containing 13 CRFGs, which, after grouping based on risk score, revealed that the LUAD high-risk group exhibited poor prognosis. Nomogram confirmed that it could be an independent risk factor for LUAD, and ROC curves and DCA validated the validity of the model. Further analysis showed that the three prognostic biomarkers (LIFR, CAV1, TFAP2A) were significantly correlated with immunization. Meanwhile, we found that a LINC00324/miR-200c-3p/TFAP2A regulatory axis could be involved in the progression of LUAD. In conclusion, our report reveals that CRFGs are well correlated with LUAD and provide new ideas for the construction of clinical prognostic tools, immunotherapy, and targeted therapy for LUAD.

Comprehensive analysis of Cuproplasia and immune microenvironment in lung adenocarcinoma

“…This, in turn, promotes the downregulation of Fe-S cluster proteins, inducing protein-toxic stress and ultimately resulting in cell death ( Antsotegi-Uskola et al, 2020 ). The study of cuproptosis has piqued the interest of researchers, and some studies based on extensive transcriptome data have shed light on the mechanism of copper-induced cell death in lung adenocarcinoma (LUAD) ( Wang X. et al, 2023 ; Wang T. et al, 2023 ; Ma et al, 2023 ). The recent evolution of perspectives on Cuproplasia may pave the way for novel avenues of research into the role of copper in tumorigenesis.…”

Identification of New Prognostic Genes and Construction of a Prognostic Model for Lung Adenocarcinoma

“…Researchers have developed several risk score models to predict the prognosis of LUAD patients based on different biomolecules such as immune checkpoints [19], lncR-NAs [20], ferroptosis-related genes [21], cuproptosis-related genes [22], DNA methylation [23], and RNA binding proteins [24]. Wang and colleagues constructed a prognostic model based on 13 cuproptosis-related ferroptosis genes (CRFGs), which were narrowed down from differentially expressed CRFGs in LUAD samples by univariate Cox regression analysis and LASSO Cox regression analysis, and included three genes associated with immune checkpoints.…”

“…Wang and colleagues constructed a prognostic model based on 13 cuproptosis-related ferroptosis genes (CRFGs), which were narrowed down from differentially expressed CRFGs in LUAD samples by univariate Cox regression analysis and LASSO Cox regression analysis, and included three genes associated with immune checkpoints. The AUC of the ROC curve was 0.716 in the training group and 0.629 and 0.742 in the testing groups [22]. Xu and colleagues focused on the genes with not only differential DNA methylation status on the promoter region but also differential mRNA expression in LUAD samples.…”

Regulation of Ferroptosis in Lung Adenocarcinoma

“…In addition, bioinformatics analyses have revealed a potential clinical connection between the FRGs and LUAD patients. A prognostic model integrating several FRGs was used to predict the prognosis, mutation burden, tumor microenvironment (TME) cell infiltration characteristics, immunotherapy effects, and chemotherapy sensitivities in patients with LUAD [32][33][34][35][36][37].…”

“…Another typical ceRNA is long non-coding RNAs (lncRNAs), a large number of which act as oncogenes and against cellular ferroptosis in LUAD, including the LINC00324/miR-200c-3p/TFAP2A pathway [32], the lncRNA GSEC/miR-101-3p/CISD1 pathway [96], the LncRNA T-UCR Uc.339/miR-339/SLC7A11 pathway [97], and the LINC00336/miR-6852/CBS pathway [98]. Of these, LINC00336 is more specific.…”