Cuproptosis-related lncRNA signatures predict prognosis and immune relevance of kidney renal papillary cell carcinoma

Xie, Tongjin; Liu, Bin; Liu, Dongbo; Zhou, Yusong; Yang, Qingping; Wang, Dai; Tang, Mengjie; Liu, Wei

doi:10.3389/fphar.2022.1103986

Cited by 4 publications

(3 citation statements)

References 45 publications

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“…KIRP stands as the second most prevalent variant of renal cell carcinoma, making up around 15% of all such carcinomas(4-6). The prognosis of KIRP patients is highly variable, currently, there is no effective treatment for advanced-stage kidney renal papillary cell carcinoma (KIRP) (7)(8)(9)(10). So effective prognostic biomarkers are urgently needed for personalized treatment and follow-up strategies.…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial Fusion RNA Signature and its Impact on KIRP Prognosis and Cisplatin Sensitivity

Hou,

Jiang,

Liu

et al. 2023

Preprint

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Background Mitochondrial fusion is a vital cellular process in eukaryotic cells, playing a significant role in preserving cell function. The impact of mitochondrial fusion extends to various aspects of cellular activity, including energy production, stress response, and cell survival. A growing body of research is delving into the role of mitochondrial fusion in the emergence and advancement of cancer. As the runner-up in terms of prevalence among renal cell carcinoma types, kidney renal papillary cell carcinoma (KIRP) exhibits a diverse array of prognostic outcomes. Uncovering new prognostic biomarkers for KIRP is essential to enhancing patient recovery and tailoring individualized therapeutic approaches. Objective In this study, our goal is to examine the gene expression associated with mitochondrial fusion and construct a novel gene signature model for predicting the prognosis of kidney renal papillary cell carcinoma (KIRP), thereby contributing to improved clinical outcomes. Methods We gathered RNA sequencing information and associated clinical data for 285 individuals with kidney renal papillary cell carcinoma (KIRP) from The Cancer Genome Atlas (TCGA) database. In order to create a gene signature panel for risk identification, we utilized LASSO regression analysis and multivariate Cox regression analysis on differentially expressed genes (BNIP3, GDAP1, MIEF2, and PRKN) associated with mitochondrial fusion. To predict immunotherapeutic responses in KIRP tumors, we conducted an array of assessments including scores for checkpoint inhibitor immunotherapy, tumor mutation burden (TMB), TIDE, and the tumor microenvironment (TME). This was integrated with our work predicting chemotherapeutic responses based on RNA-sequencing expression profiles and related clinical data from the TCGA dataset. By utilizing the GDSC database and the R package "prophetic", we estimated each sample's IC50 via ridge regression, considered combat batch effects and tissue types, and summarized duplicate gene expression as mean values. All computations were conducted within the R foundation's version 4.0.3 for statistical computing. To uncover the relationship between the gene signature and Cisplatin, we performed the correlation analysis between them and selected MIEF2 for further in vitro. Both loss-of- and gain-of-function research was performed to examine the impact of MIEF2 on therapeutic response to Cisplatin using KIRP cell line Caki-2 and ACHN. Results We identified 31 potential genes related to mitochondrial fusion. Four mitochondrial fusion-related genes (BNIP3, GDAP1, MIEF2, and PRKN) showed a significant correlation with overall survival. We constructed a risk score model predicated on the expression levels of these genes, which categorized patients into high- and low-risk groups showing significant differences in overall survival. The area under the ROC curve (AUC) for the risk score was 0.782, indicating its robust predictive performance. The RNA signature related to mitochondrial fusion was validated as an independent predictor of prognosis (P = 0.011, HR = 1.063, and 95% CI = 1.014–1.114). Additionally, our findings suggest that this model demonstrates significant potential in predicting cisplatin sensitivity in KIRP. By loss-of- and gain-of-function research targeting MIEF2 in vitro, we further confirmed that patients in the high-risk group who showed lower expression of MIEF2 were more sensitive to Cisplatin compared to the patients in the low-risk group. Conclusion We developed a novel mitochondrial fusion RNA signature that effectively predicts the prognosis of KIRP patients. This signature could serve as a valuable tool for guiding personalized treatment and follow-up strategies in clinical practice.

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Section: Introductionmentioning

confidence: 99%

Mitochondrial Fusion RNA Signature and its Impact on KIRP Prognosis and Cisplatin Sensitivity

Hou,

Jiang,

Liu

et al. 2023

Preprint

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“…For example, a risk model constructed based on eight lncRNAs, including RNF139-AS1, LINC00996, NR2F2-AS1, AL590428.1, SEC24B-AS1, AC006566.1, UBE2Q1-AS1, and AL021978.1, could be used as an independent prognostic indicator for bladder urothelial carcinoma [ 27 ]. The same lncRNA profile associated with cuproptosis could be used to predict the prognosis and immune relevance of kidney renal papillary cell carcinoma, providing new potential therapeutic targets and prognostic markers for kidney renal papillary cell carcinoma patients [ 28 ]; however, the regulation mechanism of lncRNAs on cuproptosis-related genes in HCC is still unclear. Further analysis of cuprotosis-related lncRNAs can provide more diagnostic, prognostic, and therapeutic targets for patients with liver cancer; therefore, the identification of lncRNAs related to cuproptosis-related genes is of great significance for the clarification of underlying mechanisms of hepatocarcinogenesis and the investigation of new therapeutic targets.…”

Section: Introductionmentioning

confidence: 99%

Creation of a Prognostic Model Using Cuproptosis-Associated Long Noncoding RNAs in Hepatocellular Carcinoma

Yang,

Jia,

et al. 2023

IJMS

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Cuproptosis is an unusual form of cell death caused by copper accumulation in mitochondria. Cuproptosis is associated with hepatocellular carcinoma (HCC). Long noncoding RNAs (LncRNAs) have been shown to be effective prognostic biomarkers, yet the link between lncRNAs and cuproptosis remains unclear. We aimed to build a prognostic model of lncRNA risk and explore potential biomarkers of cuproptosis in HCC. Pearson correlations were used to derive lncRNAs co-expressed in cuproptosis. The model was constructed using Cox, Lasso, and multivariate Cox regressions. Kaplan–Meier survival analysis, principal components analysis, receiver operating characteristic curve, and nomogram analyses were carried out for validation. Seven lncRNAs were identified as prognostic factors. A risk model was an independent prognostic predictor. Among these seven lncRNAs, prostate cancer associated transcript 6 (PCAT6) is highly expressed in different types of cancer, activating Wnt, PI3K/Akt/mTOR, and other pathways; therefore, we performed further functional validation of PCAT6 in HCC. Reverse transcription–polymerase chain reaction results showed that PCAT6 was aberrantly highly expressed in HCC cell lines (HepG2 and Hep3B) compared to LO2 (normal hepatocytes). When its expression was knocked down, cells proliferated and migrated less. PCAT6 might be a potential biomarker for predicting prognosis in HCC.

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“…In addition, another study found that lncRNAs can be used as prognostic markers for tumors [19]. Recently, some studies found that lncRNAs were related to cuproptosis in many tumors, such as lung adenocarcinoma, hepatocellular carcinoma, osteosarcoma, kidney renal papillary cell carcinoma, and so on [20][21][22][23][24]. Therefore, it is necessary to develop prognostic biomarkers for early diagnosis and treatment by establishing lncRNA models in BLCA.…”

Section: Introductionmentioning

confidence: 99%

A novel cuproptosis-related lncRNAs signature predicts prognosis in bladder cancer

Wu,

Chen,

Cao

et al. 2023

Aging

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This study constructed a novel cuproptosis-related lncRNAs signature to predict the prognosis of BLCA patients. The Cancer Genome Atlas (TCGA) database was used to retrieve the RNA-seq data together with the relevant clinical information. The cuproptosis-related genes were first discovered. The cuproptosis-related lncRNAs were then acquired by univariate, the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis to create a predictive signature. An eight cuproptosis-related lncRNAs (AC005261.1, AC008074.2, AC021321.1, AL024508.2, AL354919.2, ARHGAP5-AS1, LINC01106, LINC02446) predictive signature was created. Compared with the low-risk group, the prognosis was poorer for the high-risk group. The signature served as an independent overall survival (OS) predictor. Receiver operating characteristic (ROC) curve indicated that the signature demonstrated superior predictive ability, as evidenced by the area under the curve (AUC) of 0.782 than the clinicopathological variables. When we performed a subgroup analysis of the different variables, the high-risk group’s OS for BLCA patients was lower than that of the low-risk group’s patients. Gene Set Enrichment Analysis (GSEA) showed that high-risk groups were clearly enriched in many immune-related biological processes and tumor-related signaling pathways. Single sample gene set enrichment analysis (ssGSEA) revealed that the immune infiltration level was different between the two groups. Finally, quantitative RT-PCR showed that AC005261.1, AC021321.1, AL024508.2, LINC02446 and LINC01106 were lowly expressed in tumor cells, while ARHGAP5-AS1 showed the opposite trend. In summary, the predictive signature can independently predict the prognosis and provide clinical treatment guidance for BLCA patients.

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Cuproptosis-related lncRNA signatures predict prognosis and immune relevance of kidney renal papillary cell carcinoma

Cited by 4 publications

References 45 publications

Mitochondrial Fusion RNA Signature and its Impact on KIRP Prognosis and Cisplatin Sensitivity

Mitochondrial Fusion RNA Signature and its Impact on KIRP Prognosis and Cisplatin Sensitivity

Creation of a Prognostic Model Using Cuproptosis-Associated Long Noncoding RNAs in Hepatocellular Carcinoma

A novel cuproptosis-related lncRNAs signature predicts prognosis in bladder cancer

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