Top

Cancer Cell International

Published in:

Open Access 01-12-2022 | Biomarkers | Research

Identification and validation of cuproptosis-related LncRNA signatures as a novel prognostic model for head and neck squamous cell cancer

Authors: Xiajing Liu, Wenwei Cheng, Heqing Li, Yexun Song

Published in: Cancer Cell International | Issue 1/2022

Abstract

Background

Head and neck squamous cell cancer (HNSCC) is a common malignant cancer. We aimed to explore prognostic cuproptosis-related lncRNAs (CRLs) and prognostic risk models for HNSCC.

Methods

The transcriptome profiles and clinical data were obtained from the TCGA database, and 19-cuproptosis-related genes (CRGs) were acquired from previous studies. Then, the prognostic model based on seven CRLs was established. We analysed its value to evaluate the prognosis, drug sensitivity, and tumour immune functions of patients with HNSCC. Finally, we used quantitative reverse transcription polymerase chain reaction (qRT‒PCR) to validate the seven CRLs.

Results

We established a 7-CRL signature. Kaplan‒Meier (K–M) curve analysis demonstrated a significantly preferable prognosis in the low-risk group. Multivariate Cox regression analysis revealed that the risk score could serve as an independent prognostic factor. Nomogram, ROC curve, and principal component analysis indicated that the signature presented significant predictive capability. Moreover, most of the high-risk group showed lower levels of IC₅₀ for certain chemotherapy drugs, such as cisplatin, cytarabine, docetaxel, doxorubicin, etoposide, gemcitabine, methotrexate, paclitaxel, and dasatinib. Finally, the expression of AP001372.2, MIR9-3HG, AL160314.2, POLH-AS1, and AL109936.2 was upregulated, while AC090587.1 and WDFY3-AS2 were downregulated in HNSCC cell lines compared with normal cell lines by qRT‒PCR.

Conclusions

The 7-CRL signature was presented to be a novel biomarker for predicting prognosis for HNSCC.

Available only for authorised users

Kocarnik JM, Compton K, Dean FE, Fu W, Gaw BL, Harvey JD, et al. Cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life years for 29 cancer groups from 2010 to 2019: a systematic analysis for the global burden of disease study 2019. JAMA Oncol. 2022;8(3):420–44.CrossRefPubMed

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer J Clin. 2021;71(3):209–49.

Chow LQM. Head and neck cancer. N Engl J Med. 2020;382(1):60–72.CrossRefPubMed

Kim BE, Nevitt T, Thiele DJ. Mechanisms for copper acquisition, distribution and regulation. Nat Chem Biol. 2008;4(3):176–85.CrossRefPubMed

Ge EJ, Bush AI, Casini A, Cobine PA, Cross JR, DeNicola GM, et al. Connecting copper and cancer: from transition metal signalling to metalloplasia. Nat Rev Cancer. 2022;22(2):102–13.CrossRefPubMed

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.CrossRefPubMed

Ding X, Jiang M, Jing H, Sheng W, Wang X, Han J, 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.CrossRefPubMed

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.CrossRefPubMed

Stepien M, Jenab M, Freisling H, Becker NP, Czuban M, Tjønneland A, et al. Pre-diagnostic copper and zinc biomarkers and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort. Carcinogenesis. 2017;38(7):699–707.CrossRefPubMed

10.

Chen F, Wang J, Chen J, Yan L, Hu Z, Wu J, et al. Serum copper and zinc levels and the risk of oral cancer: a new insight based on large-scale case–control study. Oral Dis. 2019;25(1):80–6.CrossRefPubMed

11.

Aubert L, Nandagopal N, Steinhart Z, Lavoie G, Nourreddine S, Berman J, et al. Copper bioavailability is a KRAS-specific vulnerability in colorectal cancer. Nat Commun. 2020;11(1):3701.CrossRefPubMedPubMedCentral

12.

Tsvetkov P, Coy S, Petrova B, Dreishpoon M, Verma A, Abdusamad M, et al. Copper induces cell death by targeting lipoylated TCA cycle proteins. Science. 2022;375(6586):1254–61.CrossRefPubMedPubMedCentral

13.

Li ZX, Zheng ZQ, Yang PY, Lin L, Zhou GQ, Lv JW, et al. WTAP-mediated m(6)A modification of lncRNA DIAPH1-AS1 enhances its stability to facilitate nasopharyngeal carcinoma growth and metastasis. Cell Death Differ. 2022;29(6):1137–51.CrossRefPubMed

14.

Mi JX, Zhang YN, Lai Z, Li W, Zhou L, Zhong F. Principal component analysis based on nuclear norm minimization. Neural Netw. 2019;118:1–16.CrossRefPubMed

15.

Robinson MD, McCarthy DJ, Smyth GK. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics. 2010;26(1):139–40.CrossRefPubMed

16.

Wu T, Hu E, Xu S, Chen M, Guo P, Dai Z, et al. clusterProfiler 4.0: a universal enrichment tool for interpreting omics data. Innovation (Camb). 2021;2(3):100141.

17.

Samstein RM, Lee CH, Shoushtari AN, Hellmann MD, Shen R, Janjigian YY, et al. Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nat Genet. 2019;51(2):202–6.CrossRefPubMedPubMedCentral

18.

Wang X, Li H, Li W, Xie J, Wang F, Peng X, et al. The role of Caspase-1/GSDMD-mediated pyroptosis in Taxol-induced cell death and a Taxol-resistant phenotype in nasopharyngeal carcinoma regulated by autophagy. Cell Biol Toxicol. 2020;36(5):437–57.CrossRefPubMed

19.

Bock FJ, Tait SWG. Mitochondria as multifaceted regulators of cell death. Nat Rev Mol Cell Biol. 2020;21(2):85–100.CrossRefPubMed

20.

Zhang H, Deng T, Liu R, Ning T, Yang H, Liu D, et al. CAF secreted miR-522 suppresses ferroptosis and promotes acquired chemo-resistance in gastric cancer. Mol Cancer. 2020;19(1):43.CrossRefPubMedPubMedCentral

21.

Cox C, Merajver SD, Yoo S, Dick RD, Brewer GJ, Lee JS, et al. Inhibition of the growth of squamous cell carcinoma by tetrathiomolybdate-induced copper suppression in a murine model. Arch Otolaryngol Head Neck Surg. 2003;129(7):781–5.CrossRefPubMed

22.

Cox C, Teknos TN, Barrios M, Brewer GJ, Dick RD, Merajver SD. The role of copper suppression as an antiangiogenic strategy in head and neck squamous cell carcinoma. Laryngoscope. 2001;111(4 Pt 1):696–701.CrossRefPubMed

23.

Shanbhag VC, Gudekar N, Jasmer K, Papageorgiou C, Singh K, Petris MJ. Copper metabolism as a unique vulnerability in cancer. Biochim Biophys Acta Mol Cell Res. 2021;1868(2): 118893.CrossRefPubMed

24.

Tang Y, Li C, Zhang YJ, Wu ZH. Ferroptosis-related long non-coding RNA signature predicts the prognosis of Head and neck squamous cell carcinoma. Int J Biol Sci. 2021;17(3):702–11.CrossRefPubMedPubMedCentral

25.

Ni S, Hong J, Li W, Ye M, Li J. Construction of a cuproptosis-related lncRNA signature for predicting prognosis and immune landscape in osteosarcoma patients. Cancer Med. 2022. https://doi.org/10.1002/cam4.5214

26.

Wang F, Lin H, Su Q, Li C. Cuproptosis-related lncRNA predict prognosis and immune response of lung adenocarcinoma. World J Surg Oncol. 2022;20(1):275.CrossRefPubMedPubMedCentral

27.

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.CrossRefPubMedPubMedCentral

28.

Woo SR, Corrales L, Gajewski TF. The STING pathway and the T cell-inflamed tumor microenvironment. Trends Immunol. 2015;36(4):250–6.CrossRefPubMedPubMedCentral

29.

Leader AM, Grout JA, Maier BB, Nabet BY, Park MD, Tabachnikova A, et al. Single-cell analysis of human non-small cell lung cancer lesions refines tumor classification and patient stratification. Cancer Cell. 2021;39(12):1594-609.e12.CrossRefPubMed

30.

Negrao MV, Skoulidis F, Montesion M, Schulze K, Bara I, Shen V, et al. Oncogene-specific differences in tumor mutational burden, PD-L1 expression, and outcomes from immunotherapy in non-small cell lung cancer. J Immunother Cancer. 2021;9(8): e002891.

31.

Jiang W, Song Y, Zhong Z, Gao J, Meng X. Ferroptosis-related long non-coding RNA signature contributes to the prediction of prognosis outcomes in head and neck squamous cell carcinomas. Front Genet. 2021;12: 785839.CrossRefPubMedPubMedCentral

32.

Zhang Z, Zhang W, Wang Y, Wan T, Hu B, Li C, et al. Construction and validation of a ferroptosis-related lncRNA signature as a novel biomarker for prognosis, immunotherapy and targeted therapy in hepatocellular carcinoma. Front Cell Dev Biol. 2022;10: 792676.CrossRefPubMedPubMedCentral

33.

Zheng J, Zhou Z, Qiu Y, Wang M, Yu H, Wu Z, et al. A prognostic ferroptosis-related lncRNAs signature associated with immune landscape and radiotherapy response in glioma. Front Cell Dev Biol. 2021;9: 675555.CrossRefPubMedPubMedCentral

34.

Wang W, Ye Y, Zhang X, Ye X, Liu C, Bao L. Construction of a necroptosis-associated long non-coding RNA signature to predict prognosis and immune response in hepatocellular carcinoma. Front Mol Biosci. 2022;9: 937979.CrossRefPubMedPubMedCentral

35.

Li F, Liang Y, Ying P. Knockdown of MIR9‑3HG inhibits proliferation and promotes apoptosis of cervical cancer cells by miR‑498 via EP300. Mol Med Rep. 2021. https://doi.org/10.3892/mmr.2021.12388

Title: Identification and validation of cuproptosis-related LncRNA signatures as a novel prognostic model for head and neck squamous cell cancer
Authors: Xiajing Liu
Wenwei Cheng
Heqing Li
Yexun Song
Publication date: 01-12-2022
Publisher: BioMed Central
Keyword: Biomarkers
Published in: Cancer Cell International / Issue 1/2022
Electronic ISSN: 1475-2867
DOI: https://doi.org/10.1186/s12935-022-02762-0

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2022

A pan-cancer analysis of thioredoxin-interacting protein as an immunological and prognostic biomarker

Ursolic acid: a natural modulator of signaling networks in different cancers

A synthesized olean-28,13β-lactam targets YTHDF1-GLS1 axis to induce ROS-dependent metabolic crisis and cell death in pancreatic adenocarcinoma

Strategies to overcome the main challenges of the use of exosomes as drug carrier for cancer therapy

Clinical usefulness and acceleratory effect of macrophage inhibitory cytokine-1 on biliary tract cancer: an experimental biomarker analysis

Establishment and validation of a novel invasion-related gene signature for predicting the prognosis of ovarian cancer

Keynote webinar | Spotlight on antibody–drug conjugates in cancer