基于4个铜死亡基因的风险模型在肾透明细胞癌中的预后价值及免疫治疗药物研究

郭金帅; 丁昊; 吴鹏宇; 辛子怡; 李建新; 曹现秀; 马振海

doi:10.24920/004223

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基于4个铜死亡基因的风险模型在肾透明细胞癌中的预后价值及免疫治疗药物研究

中国医学科学杂志（英文版） 2023年38卷第3期页码：191-205

论著 | Updated：2024-11-26

- 基于4个铜死亡基因的风险模型在肾透明细胞癌中的预后价值及免疫治疗药物研究
- Affiliations：
  
  1. 1Department of Breast Surgery, Breast Cancer Key Lab of Dalian, the Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116027, China
  2. 2Department of General Surgery, the Hospital of Pyongyang Medical University, D.P.R. Korea
- Author bio：
  
  * 马振海, Email: mazhenhai@dmu.edu.cn。
- Funds：
  
  辽宁省自然科学基金(20170540254)
- DOI：10.24920/004223
  中图分类号：
- 收稿日期：2023-03-16，
  
  录用日期：2023-6-12，
  
  网络出版日期：2023-07-10，
  
  纸质出版日期：2023-09-30
- Accepted：
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郭金帅, 丁昊, 吴鹏宇, 等. 基于4个铜死亡基因的风险模型在肾透明细胞癌中的预后价值及免疫治疗药物研究[J]. 中国医学科学杂志（英文版）, 2023,38(3):191-205.

Jin-Shuai Guo, Hao Ding, Peng-Yu Wu, et al. Cuproptosis-Related 4-Gene Risk Model for Predicting Immunotherapy Drug Response and Prognosis of Kidney Renal Clear Cell Carcinoma[J]. Chinese medical sciences journal, 2023, 38(3): 191-205.
郭金帅, 丁昊, 吴鹏宇, 等. 基于4个铜死亡基因的风险模型在肾透明细胞癌中的预后价值及免疫治疗药物研究[J]. 中国医学科学杂志（英文版）, 2023,38(3):191-205. DOI： 10.24920/004223.

Jin-Shuai Guo, Hao Ding, Peng-Yu Wu, et al. Cuproptosis-Related 4-Gene Risk Model for Predicting Immunotherapy Drug Response and Prognosis of Kidney Renal Clear Cell Carcinoma[J]. Chinese medical sciences journal, 2023, 38(3): 191-205. DOI： 10.24920/004223.

摘要

目的

肾透明细胞癌（kidney renal clear cell carcinoma，KIRC）是最常见的肾恶性肿瘤之一，死亡率较高。铜死亡是一种新的细胞死亡形式，通过蛋白质脂质化导致蛋白质毒性应激反应和细胞死亡。目前，很少有研究能够充分解释铜死亡相关基因（cuproptosis-related genes，CRGs）在KIRC发生发展中的潜在作用。

方法

利用来自The Cancer Genome Atlas（TCGA）数据库中的KIRC患者的RNA测序数据和相应的临床信息筛选差异表达的CRGs。通过单因素、多因素Cox比例回归分析和LASSO Cox 回归分析构建预后风险模型。使用来自Gene Expression Omnibus（GEO）数据库的数据验证模型。采用Kaplan-Meier（KM）分析和受试者工作特征（ROC）曲线来预测KIRC患者的预后。利用功能富集分析来探索其内部机制。采用单样本基因集富集分析（single-sample gene set enrichment analysis，ssGSEA）、肿瘤免疫功能障碍和排斥（Tumour Immune Dysfunction and Exclusion，TIDE）评分和药物敏感性分析进行免疫相关功能分析。

结果

我们建立了一个由4个CRGs（

DBT

、

DLAT

、

LIAS

和

PDHB

）组成的预后风险模型来预测KIRC患者的总生存期（overall survival，OS）。生存分析的结果显示，与低风险组患者相比，高风险组患者的OS显著降低。KIRC患者的1、3、5年的ROC曲线下面积（AUC）分别为0.691、0.618和0.614。功能富集分析表明，CRGs在三羧酸循环相关过程和代谢相关途径中显著富集。索拉非尼、阿霉素、恩贝酸和长春瑞滨对高风险组的患者敏感性更高。

结论

我们构建了一个简洁有效的CRGs风险模型来评估KIRC患者的预后，这可能为KIRC提供一个新的诊断和治疗方向。

Abstract

Background

Kidney renal clear cell carcinoma (KIRC) is one of the most common renal malignancies with a high mortality rate. Cuproptosis

a novel form of cell death

is strongly linked to mitochondrial metabolism and is mediated by protein lipoylation

leading to a proteotoxic stress response and cell death. To date

few studies have ellucidated the holistic role of cuproptosis-related genes (CRGs) in the pathogenesis of KIRC.

Methods

We comprehensively and completely analyzed the RNA sequencing data and corresponding clinical information from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We screened for differentially expressed CRGs and constructed a prognostic risk model using univariate and multivariate Cox proportional regression analyses. Kaplan-Meier analysis was performed and receiver operating characteristic (ROC) curves were plotted to predict the prognosis of KIRC patients. Functional enrichment analysis was utilized to explore the internal mechanisms. Immune-related functions were analyzed using single-sample gene set enrichment analysis (ssGSEA)

tumour immune dysfunction and exclusion (TIDE) scores

and drug sensitivity analysis.

Results

We established a concise prognostic risk model consisting of four CRGs (DBT

DLAT

LIAS and PDHB) to predict the overall survival (OS) in KIRC patients. The results of the survival analysis indicated a significantly lower OS in the high-risk group as compared to the patients in the low-risk group. The area under the time-dependent ROC curve (AUC) at 1

and 5 year was 0.691

0.618

and 0.614 in KIRC. Functional enrichment analysis demonstrated that CRGs were significantly enriched in tricarboxylic acid (TCA) cycle-related processes and metabolism-related pathways. Sorafenib

doxorubicin

embelin

and vinorelbine were more sensitive in the high-risk group.

Conclusions

We constructed a concise CRGs risk model to evaluate the prognosis of KIRC patients and this may be a new direction for the diagnosis and treatment of KIRC.

关键词

Keywords

references

Siegel RL , Miller KD , Fuchs HE , et al . Cancer statistics, 2022 . CA Cancer J Clin 2022 ; 72 ( 1 ): 7 - 33 . doi: 10.3322/caac.21708 https://dx.doi.org/10.3322/caac.21708 . https://acsjournals.onlinelibrary.wiley.com/toc/15424863/72/1 https://acsjournals.onlinelibrary.wiley.com/toc/15424863/72/1

Ljungberg B , Bensalah K , Canfield S , et al . EAU guidelines on renal cell carcinoma: 2014 update . Eur Urol 2015 ; 67 ( 5 ): 913 - 24 . doi: 10.1016/j.eururo.2015.01.005 https://dx.doi.org/10.1016/j.eururo.2015.01.005 .

Rini BI , Campbell SC , Escudier B . Renal cell carcinoma . Lancet 2009 ; 373 ( 9669 ): 1119 - 32 . doi: 10.1016/s0140-6736(09)60229-4 https://dx.doi.org/10.1016/s0140-6736(09)60229-4 .

Zhang C , Chen L , Liu Y , et al. Downregulated METTL14 accumulates BPTF that reinforces super-enhancers and distal lung metastasis via glycolytic reprogramming in renal cell carcinoma . Theranostics 2021 ; 11 ( 8 ): 3676 - 93 . doi: 10.7150/thno.55424 https://dx.doi.org/10.7150/thno.55424 .

Colbert LE , Fisher SB , Balci S , et al . High nuclear hypoxia-inducible factor 1 alpha expression is a predictor of distant recurrence in patients with resected pancreatic adenocarcinoma . Int J Radiat Oncol Biol Phys 2015 ; 91 ( 3 ): 631 - 9 . doi: 10.1016/j.ijrobp.2014.11.004 https://dx.doi.org/10.1016/j.ijrobp.2014.11.004 . https://linkinghub.elsevier.com/retrieve/pii/S0360301614043685 https://linkinghub.elsevier.com/retrieve/pii/S0360301614043685

Elfiky AA , Aziz SA , Conrad PJ , et al . Characterization and targeting of phosphatidylinositol-3 kinase (PI3K) and mammalian target of rapamycin (mTOR) in renal cell cancer . J Transl Med 2011 ; 9 : 133 . doi: 10.1186/1479-5876-9-133 https://dx.doi.org/10.1186/1479-5876-9-133 .

Chen L , Luo Y , Wang G , et al . Prognostic value of a gene signature in clear cell renal cell carcinoma . J Cell Physiol 2019 ; 234 ( 7 ): 10324 - 35 . doi: 10.1002/jcp.27700 https://dx.doi.org/10.1002/jcp.27700 .

Kim BE , Nevitt T , Thiele DJ . Mechanisms for copper acquisition, distribution and regulation . Nat Chem Biol 2008 ; 4 ( 3 ): 176 - 85 . doi: 10.1038/nchembio.72 https://dx.doi.org/10.1038/nchembio.72 .

Tisato F , Marzano C , Porchia M , et al . Copper in diseases and treatments, and copper-based anticancer strategies . Med Res Rev 2010 ; 30 ( 4 ): 708 - 49 . doi: 10.1002/med.20174 https://dx.doi.org/10.1002/med.20174 .

Caruano-Yzermans AL , Bartnikas TB , Gitlin JD . Mechanisms of the copper-dependent turnover of the copper chaperone for superoxide dismutase . J Biol Chem 2006 ; 281 ( 19 ): 13581 - 87 . doi: 10.1074/jbc.M601580200 https://dx.doi.org/10.1074/jbc.M601580200 .

Carneiro BA , El-Deiry WS . Targeting apoptosis in cancer therapy . Nat Rev Clin Oncol 2020 ; 17 ( 7 ): 395 - 417 . doi: 10.1038/s41571-020-0341-y https://dx.doi.org/10.1038/s41571-020-0341-y .

Weinlich R , Oberst A , Beere HM , et al . Necroptosis in development, inflammation and disease . Nat Rev Mol Cell Biol 2017 ; 18 ( 2 ): 127 - 36 . doi: 10.1038/nrm.2016.149 https://dx.doi.org/10.1038/nrm.2016.149 .

Bergsbaken T , Fink SL , Cookson BT . Pyroptosis: host cell death and inflammation . Nat Rev Microbiol 2009 ; 7 ( 2 ): 99 - 109 . doi: 10.1038/nrmicro2070 https://dx.doi.org/10.1038/nrmicro2070 .

Dixon SJ , Lemberg KM , Lamprecht MR , et al . Ferroptosis: an iron-dependent form of nonapoptotic cell death . Cell 2012 ; 149 ( 5 ): 1060 - 72 . doi: 10.1016/j.cell.2012.03.042 https://dx.doi.org/10.1016/j.cell.2012.03.042 .

Tsvetkov P , Coy S , Petrova B , et al . Copper induces cell death by targeting lipoylated TCA cycle proteins . Science 2022 ; 375 ( 6586 ): 1254 - 61 . doi: 10.1126/science.abf0529 https://dx.doi.org/10.1126/science.abf0529 .

Ge EJ , Bush AI , Casini A , et al . Connecting copper and cancer: from transition metal signalling to metalloplasia . Nat Rev Cancer 2022 ; 22 ( 2 ): 102 - 13 . doi: 10.1038/s41568-021-00417-2 https://dx.doi.org/10.1038/s41568-021-00417-2 .

Brady DC , Crowe MS , Greenberg DN , et al . Copper chelation inhibits BRAF(V600E)-driven melanomagenesis and counters resistance to BRAF(V600E) and MEK1/2 inhibitors . Cancer Res 2017 ; 77 ( 22 ): 6240 - 52 . doi: 10.1158/0008-5472.Can-16-1190 https://dx.doi.org/10.1158/0008-5472.Can-16-1190 . https://aacrjournals.org/cancerres/article/77/22/6240/624830/Copper-Chelation-Inhibits-BRAFV600E-Driven https://aacrjournals.org/cancerres/article/77/22/6240/624830/Copper-Chelation-Inhibits-BRAFV600E-Driven

Yip NC , Fombon IS , Liu P , et al . Disulfiram modulated ROS-MAPK and NFκB pathways and targeted breast cancer cells with cancer stem cell-like properties . Br J Cancer 2011 ; 104 ( 10 ): 1564 - 74 . doi: 10.1038/bjc.2011.126 https://dx.doi.org/10.1038/bjc.2011.126 .

Tsang T , Posimo JM , Gudiel AA , et al . Copper is an essential regulator of the autophagic kinases ULK1/ 2 to drive lung adenocarcinoma . Nat Cell Biol 2020 ; 22 ( 4 ): 412 - 24 . doi: 10.1038/s41556-020-0481-4 https://dx.doi.org/10.1038/s41556-020-0481-4 .

Xiong K , Zhou Y , Karges J , et al . Autophagy-dependent apoptosis induced by apoferritin-Cu(II) nanoparticles in multidrug-resistant colon cancer cells . ACS Appl Mater Interfaces 2021 ; 13 ( 33 ): 38959 - 68 . doi: 10.1021/acsami.1c07223 https://dx.doi.org/10.1021/acsami.1c07223 . https://pubs.acs.org/doi/10.1021/acsami.1c07223 https://pubs.acs.org/doi/10.1021/acsami.1c07223

Parmar A , Pascali G , Voli F , et al . In vivo [(64)Cu]CuCl(2) PET imaging reveals activity of Dextran-Catechin on tumor copper homeostasis . Theranostics 2018 ; 8 ( 20 ): 5645 - 59 . doi: 10.7150/thno.29840 https://dx.doi.org/10.7150/thno.29840 . http://www.thno.org/v08p5645.htm http://www.thno.org/v08p5645.htm

Lun X , Wells JC , Grinshtein N , et al . Disulfiram when combined with copper enhances the therapeutic effects of temozolomide for the treatment of glioblastoma . Clin Cancer Res 2016 ; 22 ( 15 ): 3860 - 75 . doi: 10.1158/1078-0432.Ccr-15-1798 https://dx.doi.org/10.1158/1078-0432.Ccr-15-1798 .

Bandmann O , Weiss KH , Kaler SG . Wilson’s disease and other neurological copper disorders . Lancet Neurol 2015 ; 14 ( 1 ): 103 - 13 . doi: 10.1016/s1474-4422(14)70190-5 https://dx.doi.org/10.1016/s1474-4422(14)70190-5 .

Gaggelli E , Kozlowski H , Valensin D , et al . Copper homeostasis and neurodegenerative disorders (Alzheimer’s, prion, and Parkinson’s diseases and amyotrophic lateral sclerosis) . Chem Rev 2006 ; 106 ( 6 ): 1995 - 2044 . doi: 10.1021/cr040410w https://dx.doi.org/10.1021/cr040410w .

Jain S , Cohen J , Ward MM , et al . Tetrathiomolybdate-associated copper depletion decreases circulating endothelial progenitor cells in women with breast cancer at high risk of relapse . Ann Oncol 2013 ; 24 ( 6 ): 1491 - 8 . doi: 10.1093/annonc/mds654 https://dx.doi.org/10.1093/annonc/mds654 .

Cui L , Gouw AM , Lagory EL , et al . Mitochondrial copper depletion suppresses triple-negative breast cancer in mice . Nat Biotechnol 2021 ; 39 ( 3 ): 357 - 67 . doi: 10.1038/s41587-020-0707-9 https://dx.doi.org/10.1038/s41587-020-0707-9 .

Hu X , Liao S , Bai H , et al . Long noncoding RNA and predictive model to improve diagnosis of clinically diagnosed pulmonary tuberculosis . J Clin Microbiol 2020 ; 58 ( 7 ): e01973 - 19 . doi: 10.1128/jcm.01973-19 https://dx.doi.org/10.1128/jcm.01973-19 .

Wu Z , Lu Z , Li L , et al . Identification and validation of ferroptosis-related lncRNA signatures as a novel prognostic model for colon cancer . Front Immunol 2021 ; 12 : 783362 . doi: 10.3389/fimmu.2021.783362 https://dx.doi.org/10.3389/fimmu.2021.783362 . https://www.frontiersin.org/articles/10.3389/fimmu.2021.783362/full https://www.frontiersin.org/articles/10.3389/fimmu.2021.783362/full

Hong HC , Chuang CH , Huang WC , et al . A panel of eight microRNAs is a good predictive parameter for triple-negative breast cancer relapse . Theranostics 2020 ; 10 ( 19 ): 8771 - 89 . doi: 10.7150/thno.46142 https://dx.doi.org/10.7150/thno.46142 . https://www.thno.org/v10p8771.htm https://www.thno.org/v10p8771.htm

Ritchie ME , Phipson B , Wu D , et al . Limma powers differential expression analyses for RNA-sequencing and microarray studies . Nucleic Acids Res 2015 ; 43 ( 7 ): e47 . doi: 10.1093/nar/gkv007 https://dx.doi.org/10.1093/nar/gkv007 . http://academic.oup.com/nar/article/43/7/e47/2414268/limma-powers-differential-expression-analyses-for http://academic.oup.com/nar/article/43/7/e47/2414268/limma-powers-differential-expression-analyses-for

Szklarczyk D , Gable AL , Nastou KC , et al . The STRING database in 2021: customizable protein-protein networks, and functional characterization of user-uploaded gene/measurement sets . Nucleic Acids Res 2021 ; 49 ( D1 ): D605 - d12 . doi: 10.1093/nar/gkaa1074 https://dx.doi.org/10.1093/nar/gkaa1074 .

Tibshirani R . The lasso method for variable selection in the Cox model . Stat Med 1997 ; 16 ( 4 ): 385 - 95 . doi: 10.1002/(sici)1097-0258(19970228)16:4＜385::aid-sim380＞3.0.co;2-3 https://dx.doi.org/10.1002/(sici)1097-0258(19970228)16:4＜385::aid-sim380＞3.0.co;2-3 .

Yu B , Tao D . Heatmap regression via randomized rounding . IEEE Trans Pattern Anal Mach Intell 2022 ; 44 ( 11 ): 8276 - 89 . doi: 10.1109/tpami.2021.3103980 https://dx.doi.org/10.1109/tpami.2021.3103980 . https://ieeexplore.ieee.org/document/9511827/ https://ieeexplore.ieee.org/document/9511827/

Pontén F , Jirström K , Uhlen M . The Human Protein Atlas: a tool for pathology . J Pathol 2008 ; 216 ( 4 ): 387 - 93 . doi: 10.1002/path.2440 https://dx.doi.org/10.1002/path.2440 . https://pathsocjournals.onlinelibrary.wiley.com/toc/10969896/216/4 https://pathsocjournals.onlinelibrary.wiley.com/toc/10969896/216/4

Györffy B , Lanczky A , Eklund AC , et al . An online survival analysis tool to rapidly assess the effect of 22,277 genes on breast cancer prognosis using microarray data of 1,809 patients . Breast Cancer Res Treat 2010 ; 123 ( 3 ): 725 - 31 . doi: 10.1007/s10549-009-0674-9 https://dx.doi.org/10.1007/s10549-009-0674-9 . http://link.springer.com/10.1007/s10549-009-0674-9 http://link.springer.com/10.1007/s10549-009-0674-9

Nagy Á , Munkácsy G , GyŐRffy B . Pancancer survival analysis of cancer hallmark genes . Sci Rep 2021 ; 11 ( 1 ): 6047 . doi: 10.1038/s41598-021-84787-5 https://dx.doi.org/10.1038/s41598-021-84787-5 .

Wu T , Hu E , Xu S , et al . ClusterProfiler 4.0: A universal enrichment tool for interpreting omics data . Innovation (Camb) 2021 ; 2 ( 3 ): 100141 . doi: 10.1016/j.xinn.2021.100141 https://dx.doi.org/10.1016/j.xinn.2021.100141 .

Hänzelmann S , Castelo R , Guinney J . GSVA: gene set variation analysis for microarray and RNA-seq data . BMC Bioinformatics 2013 ; 14 : 7 . doi: 10.1186/1471-2105-14-7 https://dx.doi.org/10.1186/1471-2105-14-7 .

Jiang P , Gu S , Pan D , et al . Signatures of T cell dysfunction and exclusion predict cancer immunotherapy response . Nat Med 2018 ; 24 ( 10 ): 1550 - 58 . doi: 10.1038/s41591-018-0136-1 https://dx.doi.org/10.1038/s41591-018-0136-1 .

Geeleher P , Cox N , Huang RS . pRRophetic: an R package for prediction of clinical chemotherapeutic response from tumor gene expression levels . PLoS One 2014 ; 9 ( 9 ): e107468 . doi: 10.1371/journal.pone.0107468 https://dx.doi.org/10.1371/journal.pone.0107468 . https://dx.plos.org/10.1371/journal.pone.0107468 https://dx.plos.org/10.1371/journal.pone.0107468

Brady DC , Crowe MS , Turski ML , et al . Copper is required for oncogenic BRAF signalling and tumorigenesis . Nature 2014 ; 509 ( 7501 ): 492 - 6 . doi: 10.1038/nature13180 https://dx.doi.org/10.1038/nature13180 .

Liao G , Lv J , Ji A , et al . TLR3 serves as a prognostic biomarker and associates with immune infiltration in the renal clear cell carcinoma microenvironment . J Oncol 2021 ; 2021 : 3336770 . doi: 10.1155/2021/3336770 https://dx.doi.org/10.1155/2021/3336770 .

Sun Z , Jing C , Guo X , et al . Comprehensive analysis of the immune infiltrates of pyroptosis in kidney renal clear cell carcinoma . Front Oncol 2021 ; 11 : 716854 . doi: 10.3389/fonc.2021.716854 https://dx.doi.org/10.3389/fonc.2021.716854 . https://www.frontiersin.org/articles/10.3389/fonc.2021.716854/full https://www.frontiersin.org/articles/10.3389/fonc.2021.716854/full

Xing XL , Liu Y , Liu J , et al . Comprehensive analysis of ferroptosis- and immune-related signatures to improve the prognosis and diagnosis of kidney renal clear cell carcinoma . Front Immunol 2022 ; 13 : 851312 . doi: 10.3389/fimmu.2022.851312 https://dx.doi.org/10.3389/fimmu.2022.851312 . https://www.frontiersin.org/articles/10.3389/fimmu.2022.851312/full https://www.frontiersin.org/articles/10.3389/fimmu.2022.851312/full

Ahn SH , Yang HY , Tran GB , et al . Interaction of peroxiredoxin Ⅴ with dihydrolipoamide branched chain transacylase E2 (DBT) in mouse kidney under hypoxia . Proteome Sci 2015 ; 13 : 4 . doi: 10.1186/s12953-014-0061-2 https://dx.doi.org/10.1186/s12953-014-0061-2 .

Chuang DT , Chuang JL , Wynn RM . Lessons from genetic disorders of branched-chain amino acid metabolism . J Nutr 2006 ; 136 ( 1 Suppl ): 243s - 9s . doi: 10.1093/jn/136.1.243S https://dx.doi.org/10.1093/jn/136.1.243S . https://linkinghub.elsevier.com/retrieve/pii/S0022316622080427 https://linkinghub.elsevier.com/retrieve/pii/S0022316622080427

Friedrich T , Lambert AM , Masino MA , et al . Mutation of zebrafish dihydrolipoamide branched-chain transacylase E 2 results in motor dysfunction and models maple syrup urine disease . Dis Model Mech 2012 ; 5 ( 2 ): 248 - 58 . doi: 10.1242/dmm.008383 https://dx.doi.org/10.1242/dmm.008383 .

Huang X , Gan G , Wang X , et al . The HGF-MET axis coordinates liver cancer metabolism and autophagy for chemotherapeutic resistance . Autophagy 2019 ; 15 ( 7 ): 1258 - 79 . doi: 10.1080/15548627.2019.1580105 https://dx.doi.org/10.1080/15548627.2019.1580105 .

Goh WQ , Ow GS , Kuznetsov VA , et al . DLAT subunit of the pyruvate dehydrogenase complex is upregulated in gastric cancer-implications in cancer therapy . Am J Transl Res 2015 ; 7 ( 6 ): 1140 - 51 .

Thelen JJ , Muszynski MG , David NR , et al . The dihydrolipoamide S-acetyltransferase subunit of the mitochondrial pyruvate dehydrogenase complex from maize contains a single lipoyl domain . J Biol Chem 1999 ; 274 ( 31 ): 21769 - 75 . doi: 10.1074/jbc.274.31.21769 https://dx.doi.org/10.1074/jbc.274.31.21769 .

Chen S , Liu X , Peng C , et al . The phytochemical hyperforin triggers thermogenesis in adipose tissue via a Dlat-AMPK signaling axis to curb obesity . Cell Metab 2021 ; 33 ( 3 ): 565 - 80.e7 . doi: 10.1016/j.cmet.2021.02.007 https://dx.doi.org/10.1016/j.cmet.2021.02.007 .

Head RA , Brown RM , Zolkipli Z , et al . Clinical and genetic spectrum of pyruvate dehydrogenase deficiency: dihydrolipoamide acetyltransferase (E2) deficiency . Ann Neurol 2005 ; 58 ( 2 ): 234 - 41 . doi: 10.1002/ana.20550 https://dx.doi.org/10.1002/ana.20550 .

Yi X , Kim K , Yuan W , et al . Mice with heterozygous deficiency of lipoic acid synthase have an increased sensitivity to lipopolysaccharide-induced tissue injury . J Leukoc Biol 2009 ; 85 ( 1 ): 146 - 53 . doi: 10.1189/jlb.0308161 https://dx.doi.org/10.1189/jlb.0308161 . https://academic.oup.com/jleukbio/article/85/1/146/6975122 https://academic.oup.com/jleukbio/article/85/1/146/6975122

Solmonson A , Deberardinis RJ . Lipoic acid metabolism and mitochondrial redox regulation . J Biol Chem 2018 ; 293 ( 20 ): 7522 - 30 . doi: 10.1074/jbc.TM117.000259 https://dx.doi.org/10.1074/jbc.TM117.000259 .

Hendricks AL , Wachnowsky C , Fries B , et al . Characterization and reconstitution of human lipoyl synthase (LIAS) supports ISCA2 and ISCU as primary cluster donors and an ordered mechanism of cluster assembly . Int J Mol Sci 2021 ; 22 ( 4 ). doi: 10.3390/ijms22041598 https://dx.doi.org/10.3390/ijms22041598 .

Habarou F , Hamel Y , Haack TB , et al . Biallelic mutations in LIPT 2 cause a mitochondrial lipoylation defect associated with severe neonatal encephalopathy . Am J Hum Genet 2017 ; 101 ( 2 ): 283 - 90 . doi: 10.1016/j.ajhg.2017.07.001 https://dx.doi.org/10.1016/j.ajhg.2017.07.001 . https://linkinghub.elsevier.com/retrieve/pii/S0002929717302793 https://linkinghub.elsevier.com/retrieve/pii/S0002929717302793

Mayr JA , Zimmermann FA , Fauth C , et al . Lipoic acid synthetase deficiency causes neonatal-onset epilepsy, defective mitochondrial energy metabolism, and glycine elevation . Am J Hum Genet 2011 ; 89 ( 6 ): 792 - 7 . doi: 10.1016/j.ajhg.2011.11.011 https://dx.doi.org/10.1016/j.ajhg.2011.11.011 .

Okajima K , Korotchkina LG , Prasad C , et al . Mutations of the E1beta subunit gene (PDHB) in four families with pyruvate dehydrogenase deficiency . Mol Genet Metab 2008 ; 93 ( 4 ): 371 - 80 . doi: 10.1016/j.ymgme.2007.10.135 https://dx.doi.org/10.1016/j.ymgme.2007.10.135 .

Wang G , Ye Q , Ning S , et al. LncRNA MEG3 promotes endoplasmic reticulum stress and suppresses proliferation and invasion of colorectal carcinoma cells through the MEG3/miR-103a-3p/PDHB ceRNA pathway . Neoplasma 2021 ; 68 ( 2 ): 362 - 74 . doi: 10.4149/neo_2020_200813N858 https://dx.doi.org/10.4149/neo_2020_200813N858 .

Suda C , Yatabe J , Yatabe M , et al . Soluble (pro)renin receptor increased by hypoxia maintains oxidative metabolism in trophoblasts . J Mol Endocrinol 2020 ; 64 ( 3 ): 145 - 54 . doi: 10.1530/jme-19-0050 https://dx.doi.org/10.1530/jme-19-0050 .

Rowland EA , Snowden CK , Cristea IM . Protein lipoylation: an evolutionarily conserved metabolic regulator of health and disease . Curr Opin Chem Biol 2018 ; 42 : 76 - 85 . doi: 10.1016/j.cbpa.2017.11.003 https://dx.doi.org/10.1016/j.cbpa.2017.11.003 .

Patel MS , Nemeria NS , Furey W , et al . The pyruvate dehydrogenase complexes: structure-based function and regulation . J Biol Chem 2014 ; 289 ( 24 ): 16615 - 23 . doi: 10.1074/jbc.R114.563148 https://dx.doi.org/10.1074/jbc.R114.563148 .

Anderson NM , Mucka P , Kern JG , et al . The emerging role and targetability of the TCA cycle in cancer metabolism . Protein Cell 2018 ; 9 ( 2 ): 216 - 37 . doi: 10.1007/s13238-017-0451-1 https://dx.doi.org/10.1007/s13238-017-0451-1 .

Hensley CT , Faubert B , Yuan Q , et al . Metabolic heterogeneity in human lung tumors . Cell 2016 ; 164 ( 4 ): 681 - 94 . doi: 10.1016/j.cell.2015.12.034 https://dx.doi.org/10.1016/j.cell.2015.12.034 .

Liu PS , Wang H , Li X , et al . α-ketoglutarate orchestrates macrophage activation through metabolic and epigenetic reprogramming . Nat Immunol 2017 ; 18 ( 9 ): 985 - 94 . doi: 10.1038/ni.3796 https://dx.doi.org/10.1038/ni.3796 . https://www.nature.com/articles/ni.3796 https://www.nature.com/articles/ni.3796

Hatzivassiliou G , Zhao F , Bauer DE , et al . ATP citrate lyase inhibition can suppress tumor cell growth . Cancer Cell 2005 ; 8 ( 4 ): 311 - 21 . doi: 10.1016/j.ccr.2005.09.008 https://dx.doi.org/10.1016/j.ccr.2005.09.008 .

Zhang X , Wang Y , A G , et al . Pan-cancer analysis of PARP 1 alterations as biomarkers in the prediction of immunotherapeutic effects and the association of its expression levels and immunotherapy signatures . Front Immunol 2021 ; 12 : 721030 . doi: 10.3389/fimmu.2021.721030 https://dx.doi.org/10.3389/fimmu.2021.721030 . https://www.frontiersin.org/articles/10.3389/fimmu.2021.721030/full https://www.frontiersin.org/articles/10.3389/fimmu.2021.721030/full

Zhou SL , Zhou ZJ , Hu ZQ , et al . Tumor-associated neutrophils recruit macrophages and T-regulatory cells to promote progression of hepatocellular carcinoma and resistance to sorafenib . Gastroenterology 2016 ; 150 ( 7 ): 1646 - 58.e17 . doi: 10.1053/j.gastro.2016.02.040 https://dx.doi.org/10.1053/j.gastro.2016.02.040 . https://linkinghub.elsevier.com/retrieve/pii/S0016508516002316 https://linkinghub.elsevier.com/retrieve/pii/S0016508516002316

Quail DF , Joyce JA . Microenvironmental regulation of tumor progression and metastasis . Nat Med 2013 ; 19 ( 11 ): 1423 - 37 . doi: 10.1038/nm.3394 https://dx.doi.org/10.1038/nm.3394 .

Escudier B , Eisen T , Stadler WM , et al . Sorafenib in advanced clear-cell renal-cell carcinoma . N Engl J Med 2007 ; 356 ( 2 ): 125 - 34 . doi: 10.1056/NEJMoa060655 https://dx.doi.org/10.1056/NEJMoa060655 . http://www.nejm.org/doi/abs/10.1056/NEJMoa060655 http://www.nejm.org/doi/abs/10.1056/NEJMoa060655

Rini BI , Escudier B , Tomczak P , et al . Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial . Lancet 2011 ; 378 ( 9807 ): 1931 - 9 . doi: 10.1016/s0140-6736(11)61613-9 https://dx.doi.org/10.1016/s0140-6736(11)61613-9 .

Rini BI , Pal SK , Escudier BJ , et al . Tivozanib versus sorafenib in patients with advanced renal cell carcinoma (TIVO-3): a phase 3, multicentre, randomised, controlled, open-label study . Lancet Oncol 2020 ; 21 ( 1 ): 95 - 104 . doi: 10.1016/s1470-2045(19)30735-1 https://dx.doi.org/10.1016/s1470-2045(19)30735-1 .

Lakkakula JR , Gujarathi P , Pansare P , et al . A comprehensive review on alginate-based delivery systems for the delivery of chemotherapeutic agent: Doxorubicin . Carbohydr Polym 2021 ; 259 : 117696 . doi: 10.1016/j.carbpol.2021.117696 https://dx.doi.org/10.1016/j.carbpol.2021.117696 . https://linkinghub.elsevier.com/retrieve/pii/S0144861721000837 https://linkinghub.elsevier.com/retrieve/pii/S0144861721000837

Wei T , Xie XJ , Cao PL . Magnoflorine improves sensitivity to doxorubicin (DOX) of breast cancer cells via inducing apoptosis and autophagy through AKT/mTOR and p38 signaling pathways . Biomed Pharmacother 2020 ; 121 : 109139 . doi: 10.1016/j.biopha.2019.109139 https://dx.doi.org/10.1016/j.biopha.2019.109139 .

Wu Q , Li W , Zhao J , et al . Apigenin ameliorates doxorubicin-induced renal injury via inhibition of oxidative stress and inflammation . Biomed Pharmacother 2021 ; 137 : 111308 . doi: 10.1016/j.biopha.2021.111308 https://dx.doi.org/10.1016/j.biopha.2021.111308 .

Heo JY , Kim HJ , Kim SM , et al . Embelin suppresses STAT3 signaling, proliferation, and survival of multiple myeloma via the protein tyrosine phosphatase PTEN . Cancer Lett 2011 ; 308 ( 1 ): 71 - 80 . doi: 10.1016/j.canlet.2011.04.015 https://dx.doi.org/10.1016/j.canlet.2011.04.015 .

Lee YJ , Park BS , Park HR , et al . XIAP inhibitor embelin induces autophagic and apoptotic cell death in human oral squamous cell carcinoma cells . Environ Toxicol 2017 ; 32 ( 11 ): 2371 - 78 . doi: 10.1002/tox.22450 https://dx.doi.org/10.1002/tox.22450 . https://onlinelibrary.wiley.com/toc/15227278/32/11 https://onlinelibrary.wiley.com/toc/15227278/32/11

Bisogno G , De Salvo GL , Bergeron C , et al . Vinorelbine and continuous low-dose cyclophosphamide as maintenance chemotherapy in patients with high-risk rhabdomyosarcoma (RMS 2005): a multicentre, open-label, randomised, phase 3 trial . Lancet Oncol 2019 ; 20 ( 11 ): 1566 - 75 . doi: 10.1016/s1470-2045(19)30617-5 https://dx.doi.org/10.1016/s1470-2045(19)30617-5 .

Moskowitz AJ , Shah G , Schöder H , et al . Phase II trial of pembrolizumab plus gemcitabine, vinorelbine, and liposomal doxorubicin as second-line therapy for relapsed or refractory classical Hodgkin lymphoma . J Clin Oncol 2021 ; 39 ( 28 ): 3109 - 17 . doi: 10.1200/jco.21.01056 https://dx.doi.org/10.1200/jco.21.01056 . https://ascopubs.org/doi/10.1200/JCO.21.01056 https://ascopubs.org/doi/10.1200/JCO.21.01056

Chan A , Verrill M . Capecitabine and vinorelbine in metastatic breast cancer . Eur J Cancer 2009 ; 45 ( 13 ): 2253 - 65 . doi: 10.1016/j.ejca.2009.04.031 https://dx.doi.org/10.1016/j.ejca.2009.04.031 .

Kenmotsu H , Yamamoto N , Yamanaka T , et al . Randomized phase III study of pemetrexed plus cisplatin versus vinorelbine plus cisplatin for completely resected stage II to IIIA nonsquamous non-small-cell lung cancer . J Clin Oncol 2020 ; 38 ( 19 ): 2187 - 96 . doi: 10.1200/jco.19.02674 https://dx.doi.org/10.1200/jco.19.02674 .

Falvo P , Orecchioni S , Hillje R , et al . Cyclophosphamide and vinorelbine activate stem-like CD8(+) T cells and improve anti-PD-1 efficacy in triple-negative breast cancer . Cancer Res 2021 ; 81 ( 3 ): 685 - 97 . doi: 10.1158/0008-5472.Can-20-1818 https://dx.doi.org/10.1158/0008-5472.Can-20-1818 .

Zhang X , Xiong Y , Xia Q , et al . Efficacy and safety of apatinib plus vinorelbine in patients with wild-type advanced non-small cell lung cancer after second-line treatment failure: a nonrandomized clinical trial . JAMA Netw Open 2020 ; 3 ( 3 ): e201226 . doi: 10.1001/jamanetworkopen.2020.1226 https://dx.doi.org/10.1001/jamanetworkopen.2020.1226 . https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2762949 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2762949

Dagogo-Jack I , Shaw AT . Tumour heterogeneity and resistance to cancer therapies . Nat Rev Clin Oncol 2018 ; 15 ( 2 ): 81 - 94 . doi: 10.1038/nrclinonc.2017.166 https://dx.doi.org/10.1038/nrclinonc.2017.166 .

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