Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
European Journal of Medical Research
Published in: European Journal of Medical Research 1/2023

Open Access 01-12-2023 | Kidney Cancer | Research

Cuproptosis-Related Ferroptosis genes for Predicting Prognosis in kidney renal clear cell carcinoma

Authors: Gang Luo, Lini Wang, Ziyu Zheng, Baobao Gao, Chong Lei

Published in: European Journal of Medical Research | Issue 1/2023

Login to get access

Abstract

Kidney renal clear cell carcinoma (KIRC) is a main subtype of kidney cancers. Cuproptosis and ferroptosis are correlated with immune infiltration and prognosis in tumors. However, the role of Cuproptosis-related Ferroptosis genes (CRFGs) in KIRC has rarely been fully understood. Therefore, we constructed a prognostic signature based on different expression of CRFGs in KIRC. All raw data of this study were extracted from public TCGA datasets. Cuproptosis and Ferroptosis genes were collected from the previous research. Finally, a total of 36 significantly different CRFGs were identified from TCGA–KIRC cohort. Six-gene signature (TRIB3, SLC2A3, PML, CD44, CDKN2A and MIOX) was identified by LASSO Cox regression based on the significantly different CRFGs. The CRFGs signature was correlated with worse overall survival and the AUC was 0.750. Functional enrichment indicated that CRFGs were mainly enriched in metabolism, drug resistance, tumor immunity pathways. Besides, the IC50 and immune checkpoint differentially expressed between different groups. The proposed 6-CRFGs signature is a promising biomarker to predict clinical outcomes and therapeutic responses for KIRC patient.
Appendix
Available only for authorised users
Literature
1.
2.
Znaor A, Lortet-Tieulent J, Laversanne M, Jemal A, Bray F. International variations and trends in renal cell carcinoma incidence and mortality. Eur Urol. 2015;67(3):519–30.PubMedCrossRef
3.
Yin L, Li W, Xu A, et al. SH3BGRL2 inhibits growth and metastasis in clear cell renal cell carcinoma via activating hippo/TEAD1-Twist1 pathway. EBioMedicine. 2020;51: 102596.PubMedPubMedCentralCrossRef
4.
Lalani AA, McGregor BA, Albiges L, et al. Systemic treatment of metastatic clear cell renal cell carcinoma in 2018: current paradigms, use of immunotherapy, and future directions. Eur Urol. 2019;75(1):100–10.PubMedCrossRef
5.
Fendler A, Bauer D, Busch J, et al. Inhibiting WNT and NOTCH in renal cancer stem cells and the implications for human patients. Nat Commun. 2020;11(1):929.PubMedPubMedCentralCrossRef
6.
Tsvetkov P, Coy S, Petrova B, et al. Copper induces cell death by targeting lipoylated TCA cycle proteins [published correction appears in Science. Science. 2022;375(6586):1254–61.PubMedPubMedCentralCrossRef
7.
8.
Brewer GJ. Copper control as an antiangiogenic anticancer therapy: lessons from treating Wilson’s disease. Exp Biol Med (Maywood). 2001;226(7):665–73.PubMedCrossRef
9.
Larson CA, Blair BG, Safaei R, Howell SB. The role of the mammalian copper transporter 1 in the cellular accumulation of platinum-based drugs. Mol Pharmacol. 2009;75(2):324–30.PubMedCrossRef
10.
11.
Baltaci AK, Dundar TK, Aksoy F, Mogulkoc R. Changes in the serum levels of trace elements before and after the operation in thyroid cancer patients. Biol Trace Elem Res. 2017;175(1):57–64.PubMedCrossRef
12.
Basu S, Singh MK, Singh TB, Bhartiya SK, Singh SP, Shukla VK. Heavy and trace metals in carcinoma of the gallbladder. World J Surg. 2013;37(11):2641–6.PubMedCrossRef
13.
Ding X, Jiang M, Jing H, et al. Analysis of serum levels of 15 trace elements in breast cancer patients in Shandong China. Environ Sci Pollut Res Int. 2015;22(10):7930–5.PubMedCrossRef
14.
Saleh SAK, Adly HM, Abdelkhaliq AA, Nassir AM. Serum levels of selenium, zinc, copper, manganese, and iron in prostate cancer patients. Curr Urol. 2020;14(1):44–9.PubMedPubMedCentralCrossRef
15.
16.
17.
Chen P, Li X, Zhang R, et al. Combinative treatment of β-elemene and cetuximab is sensitive to KRAS mutant colorectal cancer cells by inducing ferroptosis and inhibiting epithelial-mesenchymal transformation. Theranostics. 2020;10(11):5107–19.PubMedPubMedCentralCrossRef
18.
Wang Y, Zhao G, Condello S, et al. Frizzled-7 identifies platinum-tolerant ovarian cancer cells susceptible to ferroptosis. Cancer Res. 2021;81(2):384–99.PubMedCrossRef
19.
20.
LaVaute T, Smith S, Cooperman S, et al. Targeted deletion of the gene encoding iron regulatory protein-2 causes misregulation of iron metabolism and neurodegenerative disease in mice. Nat Genet. 2001;27(2):209–14.PubMedCrossRef
21.
Gupta A, Lutsenko S. Human copper transporters: mechanism, role in human diseases and therapeutic potential. Future Med Chem. 2009;1(6):1125–42.PubMedCrossRef
22.
Wee NK, Weinstein DC, Fraser ST, Assinder SJ. The mammalian copper transporters CTR1 and CTR2 and their roles in development and disease. Int J Biochem Cell Biol. 2013;45(5):960–3.PubMedCrossRef
23.
Gao J, Zhao N, Knutson MD, Enns CA. The hereditary hemochromatosis protein, HFE, inhibits iron uptake via down-regulation of Zip14 in HepG2 cells. J Biol Chem. 2008;283(31):21462–8.PubMedPubMedCentralCrossRef
24.
25.
26.
Bian Z, Fan R, Xie L. A novel cuproptosis-related prognostic gene signature and validation of differential expression in clear cell renal cell carcinoma. Genes (Basel). 2022;13(5):851.PubMedCrossRef
27.
28.
29.
Liu Y, Liu Y, Ye S, Feng H, Ma L. Development and validation of cuproptosis-related gene signature in the prognostic prediction of liver cancer. Front Oncol. 2022;12: 985484.PubMedPubMedCentralCrossRef
30.
Bao JH, Lu WC, Duan H, et al. Identification of a novel cuproptosis-related gene signature and integrative analyses in patients with lower-grade gliomas. Front Immunol. 2022;13: 933973.PubMedPubMedCentralCrossRef
31.
Sun Z, Li T, Xiao C, et al. Prediction of overall survival based upon a new ferroptosis-related gene signature in patients with clear cell renal cell carcinoma. World J Surg Oncol. 2022;20(1):120.PubMedPubMedCentralCrossRef
32.
Yu J, Mao W, Xu B, Chen M. Construction and validation of an autophagy-related long noncoding RNA signature for prognosis prediction in kidney renal clear cell carcinoma patients. Cancer Med. 2021;10(7):2359–69.PubMedPubMedCentralCrossRef
33.
Xing Q, Ji C, Zhu B, Cong R, Wang Y. Identification of small molecule drugs and development of a novel autophagy-related prognostic signature for kidney renal clear cell carcinoma. Cancer Med. 2020;9(19):7034–51.PubMedPubMedCentralCrossRef
34.
Hong B, Zhou J, Ma K, et al. TRIB3 promotes the proliferation and invasion of renal cell carcinoma cells via activating MAPK signaling pathway. Int J Biol Sci. 2019;15(3):587–97.PubMedPubMedCentralCrossRef
35.
Liu J, Zhang W, Chuang GC, et al. Role of TRIB3 in regulation of insulin sensitivity and nutrient metabolism during short-term fasting and nutrient excess. Am J Physiol Endocrinol Metab. 2012;303(7):E908–16.PubMedPubMedCentralCrossRef
36.
Eyers PA, Keeshan K, Kannan N. tribbles in the 21st century: the evolving roles of tribbles Pseudokinases in biology and disease. Trends Cell Biol. 2017;27(4):284–98.PubMedPubMedCentralCrossRef
37.
Xu H, Wang X, Wu J, et al. Long non-coding RNA LINC01094 promotes the development of clear cell renal cell carcinoma by upregulating SLC2A3 via MicroRNA-184. Front Genet. 2020;11: 562967.PubMedPubMedCentralCrossRef
38.
39.
Lin YC, Lu LT, Chen HY, et al. SCP phosphatases suppress renal cell carcinoma by stabilizing PML and inhibiting mTOR/HIF signaling. Cancer Res. 2014;74(23):6935–46.PubMedCrossRef
40.
Zhou Q, Li J, Ge C, Chen J, Tian W, Tian H. SNX5 suppresses clear cell renal cell carcinoma progression by inducing CD44 internalization and epithelial-to-mesenchymal transition. Mol Ther Oncolytics. 2021;24:87–100.PubMedPubMedCentralCrossRef
41.
Yaghobi Z, Movassaghpour A, Talebi M, et al. The role of CD44 in cancer chemoresistance: a concise review. Eur J Pharmacol. 2021;903: 174147.PubMedCrossRef
42.
Heikaus S, van den Berg L, Kempf T, Mahotka C, Gabbert HE, Ramp U. HA14-1 is able to reconstitute the impaired mitochondrial pathway of apoptosis in renal cell carcinoma cell lines. Cell Oncol. 2008;30(5):419–33.PubMedPubMedCentral
43.
Toth C, Funke S, Nitsche V, Liverts A, Zlachevska V, Gasis M, Wiek C, Hanenberg H, Mahotka C, Schirmacher P, Heikaus S. The role of apoptosis repressor with a CARD domain (ARC) in the therapeutic resistance of renal cell carcinoma (RCC): the crucial role of ARC in the inhibition of extrinsic and intrinsic apoptotic signalling. Cell Commun Signal. 2017;15(1):16.PubMedPubMedCentralCrossRef
44.
Nientiedt M, Müller K, Nitschke K, et al. B-MYB-p53-related relevant regulator for the progression of clear cell renal cell carcinoma. J Cancer Res Clin Oncol. 2021;147(1):129–38.PubMedCrossRef
45.
Vieler M, Sanyal S. p53 Isoforms and Their Implications in Cancer. Cancers (Basel). 2018;10(9):288.PubMedCrossRef
46.
47.
Catanzaro E, Feron O, Skirtach AG, Krysko DV. Immunogenic cell death and role of nanomaterials serving as therapeutic vaccine for personalized cancer immunotherapy. Front Immunol. 2022;13:925290.PubMedPubMedCentralCrossRef
48.
Bi K, He MX, Bakouny Z, et al. Tumor and immune reprogramming during immunotherapy in advanced renal cell carcinoma. Cancer Cell. 2021;39(5):649-661.e5.PubMedPubMedCentralCrossRef
49.
Ma J, Zheng B, Goswami S, et al. PD1Hi CD8+ T cells correlate with exhausted signature and poor clinical outcome in hepatocellular carcinoma. J Immunother Cancer. 2019;7(1):331.PubMedPubMedCentralCrossRef
50.
Matsuki M, Hirohashi Y, Nakatsugawa M, et al. Tumor-infiltrating CD8+ T cells recognize a heterogeneously expressed functional neoantigen in clear cell renal cell carcinoma. Cancer Immunol Immunother. 2022;71(4):905–18.PubMedCrossRef
51.
Dong MB, Wang G, Chow RD, et al. Systematic immunotherapy target discovery using genome-scale in vivo CRISPR screens in CD8 T cells. Cell. 2019;178(5):1189-1204.e23.PubMedPubMedCentralCrossRef
52.
53.
Mucaki EJ, Zhao JZL, Lizotte DJ, Rogan PK. Predicting responses to platin chemotherapy agents with biochemically-inspired machine learning. Signal Transduct Target Ther. 2019;4:1.PubMedPubMedCentralCrossRef
54.
Risso-Ballester J, Galloux M, Cao J, et al. A condensate-hardening drug blocks RSV replication in vivo. Nature. 2021;595(7868):596–9.PubMedCrossRef
55.
Eimer S, Dugay F, Airiau K, et al. Cyclopamine cooperates with EGFR inhibition to deplete stem-like cancer cells in glioblastoma-derived spheroid cultures. Neuro Oncol. 2012;14(12):1441–51.PubMedPubMedCentralCrossRef
56.
Strasser A, Vaux DL. Cell death in the origin and treatment of cancer. Mol Cell. 2020;78(6):1045–54.PubMedCrossRef
Metadata
Title
Cuproptosis-Related Ferroptosis genes for Predicting Prognosis in kidney renal clear cell carcinoma
Authors
Gang Luo
Lini Wang
Ziyu Zheng
Baobao Gao
Chong Lei
Publication date
01-12-2023
Publisher
BioMed Central
Published in
European Journal of Medical Research / Issue 1/2023
Electronic ISSN: 2047-783X
DOI
https://doi.org/10.1186/s40001-023-01137-z

Other articles of this Issue 1/2023

European Journal of Medical Research 1/2023 Go to the issue

Research

Protective effects of paraoxonase-1, vitamin E and selenium, and oxidative stress index on the susceptibility of low density lipoprotein to oxidation in diabetic patients with/without coronary artery disease

Research

Chest computed tomography severity score is a reliable predictor of mortality in patients with chronic obstructive pulmonary disease co-infected with COVID-19

Research

The burden of critical illness among adults in a Swedish region—a population-based point-prevalence study

Review

Speech deficits in multiple sclerosis: a narrative review of the existing literature

Research

Soluble immune checkpoints are elevated in patients with primary biliary cholangitis

Research

The influence of vitamin D on handgrip strength in elderly trauma patients