Top

Discover Oncology

Published in:

Open Access 01-12-2024 | Research

Identification of a disulfidptosis-related lncRNA signature for the prognostic and immune landscape prediction in head and neck squamous cell carcinoma

Authors: Zhengyu Wei, Chongchang Zhou, Yi Fang, Hongxia Deng, Zhisen Shen

Published in: Discover Oncology | Issue 1/2024

Abstract

Purpose

Disulfidptosis, a newly identified form of cell death, is triggered by disulfide stress. Herein, a unique signature was developed based on disulfidptosis-related lncRNAs (DRlncRNAs) for the prognostic and immune landscape prediction of head and neck squamous cell carcinoma (HNSCC).

Methods

Transcriptome, somatic mutation, and clinical data were acquired at The Cancer Genome Atlas database. Individuals were partitioned into training and test cohorts at a 1:1 ratio to facilitate the development of a DRlncRNA signature using the least absolute shrinkage and selection operation method. Based on the median risk score, all HNSCC individuals were stratified into the high-risk group (HRG) and low-risk group (LRG). Kaplan–Meier survival and time-dependent receiver operating characteristic (ROC) analyses were used to estimate the prognostic value, and a nomogram was generated for survival prediction. To provide a more comprehensive assessment, the tumor microenvironment, functional enrichment, immune cell infiltration, and immunotherapeutic sensitivity were explored between LRG and HRG.

Results

A DRlncRNA signature was established with 10 DRlncRNAs. The corresponding values of areas under the ROC curves for 1–, 3–, and 5–year overall survival were 0.710, 0.692, and 0.640. A more favorable prognosis was noted in the patients with lower risk, along with higher immune scores, increased immune-related functions, and immune cell infiltration, as well as improved response to the immunotherapeutic intervention in comparison with individuals at higher risk.

Conclusion

These findings demonstrate that the developed DRlncRNA signature holds promise as a reliable prognostic marker and predictor of immunotherapy response in HNSCC patients.

Available only for authorised users

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70:7–30. https://doi.org/10.3322/caac.21590.CrossRefPubMed

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424. https://doi.org/10.3322/caac.21492.CrossRefPubMed

Ferlay J, Colombet M, Soerjomataram I, Mathers C, Parkin DM, Piñeros M, et al. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int J Cancer. 2019;144:1941–53. https://doi.org/10.1002/ijc.31937.CrossRefPubMed

Cervenka BP, Rao S, Bewley AF. Head and neck cancer and the elderly patient. Otolaryngol Clin North Am. 2018;51:741–51. https://doi.org/10.1016/j.otc.2018.03.004.CrossRefPubMed

Johnson DE, Burtness B, Leemans CR, Lui V, Bauman JE, Grandis JR. Head and neck squamous cell carcinoma. Nat Rev Dis Primers. 2020;6:92. https://doi.org/10.1038/s41572-020-00224-3.CrossRefPubMedPubMedCentral

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68:7–30. https://doi.org/10.3322/caac.21442.CrossRefPubMed

Burtness B, Harrington KJ, Greil R, Soulières D, Tahara M, de Castro G, et al. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet. 2019;394:1915–28. https://doi.org/10.1016/S0140-6736(19)32591-7.CrossRefPubMed

Ferris RL, Blumenschein G Jr, Fayette J, Guigay J, Colevas AD, Licitra L, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med. 2016;375:1856–67. https://doi.org/10.1056/NEJMoa1602252.CrossRefPubMedPubMedCentral

Hanna GJ, Lizotte P, Cavanaugh M, Kuo FC, Shivdasani P, Frieden A, et al. Frameshift events predict anti-PD-1/L1 response in head and neck cancer. JCI Insight. 2018;3: e98811. https://doi.org/10.1172/jci.insight.98811.CrossRefPubMedPubMedCentral

10.

Liu X, Nie L, Zhang Y, Yan Y, Wang C, Colic M, Olszewski K, Horbath A, Chen X, Lei G, Mao C, Wu S, Zhuang L, Poyurovsky MV, James You M, Hart T, Billadeau DD, Chen J, Gan B. Actin cytoskeleton vulnerability to disulfide stress mediates disulfidptosis. Nat Cell Biol. 2023;25:404–14. https://doi.org/10.1038/s41556-023-01091-2.CrossRefPubMedPubMedCentral

11.

Zheng P, Zhou C, Ding Y, Duan S. Disulfidptosis: a new target for metabolic cancer therapy. J Exp Clin Cancer Res. 2023;42:103. https://doi.org/10.1186/s13046-023-02675-4.CrossRefPubMedPubMedCentral

12.

Zheng T, Liu Q, Xing F, Zeng C, Wang W. Disulfidptosis: a new form of programmed cell death. J Exp Clin Cancer Res. 2023;42:137. https://doi.org/10.1186/s13046-023-02712-2.CrossRefPubMedPubMedCentral

13.

Chen H, Yang W, Li Y, Ma L, Ji Z. Leveraging a disulfidptosis-based signature to improve the survival and drug sensitivity of bladder cancer patients. Front Immunol. 2023;14:1198878. https://doi.org/10.3389/fimmu.2023.1198878.CrossRefPubMedPubMedCentral

14.

Chen Y, Xue W, Zhang Y, Gao Y, Wang Y. A novel disulfidptosis-related immune checkpoint genes signature: forecasting the prognosis of hepatocellular carcinoma. J Cancer Res Clin Oncol. 2023. https://doi.org/10.1007/s00432-023-05076-4.CrossRefPubMedPubMedCentral

15.

Feng Z, Zhao Q, Ding Y, Xu Y, Sun X, Chen Q, Zhang Y, Miao J, Zhu J. Identification a unique disulfidptosis classification regarding prognosis and immune landscapes in thyroid carcinoma and providing therapeutic strategies. J Cancer Res Clin Oncol. 2023. https://doi.org/10.1007/s00432-023-05006-4.CrossRefPubMedPubMedCentral

16.

Ghaforui-Fard S, Vafaee R, Taheri M. Taurine-upregulated gene 1: a functional long noncoding RNA in tumorigenesis. J Cell Physiol. 2019;234:17100–12. https://doi.org/10.1002/jcp.28464.CrossRefPubMed

17.

Xu C, Han P, Ren W, Dai H, Bai Y, Shen Z, Li B, Shao Y. The genetic polymorphisms in the MIR17HG gene are associated with the risk of head and neck squamous cell carcinoma in the chinese han population. Biomed Res Int. 2020;2020:2329196. https://doi.org/10.1155/2020/2329196.CrossRefPubMedPubMedCentral

18.

Wang S, Chen X, Qiao T. Long non-coding RNA MIR4435-2HG promotes the progression of head and neck squamous cell carcinoma by regulating the miR-383-5p/RBM3 axis. Oncol Rep. 2021;45:99. https://doi.org/10.3892/or.2021.8050.CrossRefPubMedPubMedCentral

19.

Cao W, Liu JN, Liu Z, Wang X, Han ZG, Ji T, Chen WT, Zou X. A three-lncRNA signature derived from the Atlas of ncRNA in cancer (TANRIC) database predicts the survival of patients with head and neck squamous cell carcinoma. Oral Oncol. 2017;65:94–101. https://doi.org/10.1016/j.oraloncology.2016.12.017.CrossRefPubMed

20.

Duan Y, Yue K, Ye B, Chen P, Zhang J, He Q, Wu Y, Lai Q, Li H, Wu Y, Jing C, Wang X. LncRNA MALAT1 promotes growth and metastasis of head and neck squamous cell carcinoma by repressing VHL through a non-canonical function of EZH2. Cell Death Dis. 2023;14:149. https://doi.org/10.1038/s41419-023-05667-6.CrossRefPubMedPubMedCentral

21.

The Cancer Genome Atlas Network. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature. 2015;517:576–82. https://doi.org/10.1038/nature14129.

22.

Zhang D, Zhang X, Liu Z, Han T, Zhao K, Xu X, Zhang X, Ren X, Qin C. An integrative multi-omics analysis based on disulfidptosis-related prognostic signature and distinct subtypes of clear cell renal cell carcinoma. Front Oncol. 2023;13:1207068. https://doi.org/10.3389/fonc.2023.1207068.CrossRefPubMedPubMedCentral

23.

Yang C, Mei H, Peng L, Jiang F, Xie B, Li J. Prognostic correlation of an autophagy-related gene signature in patients with head and neck squamous cell carcinoma. Comput Math Methods Med. 2020;2020:7397132. https://doi.org/10.1155/2020/7397132.CrossRefPubMedPubMedCentral

24.

Feng C, Liu S, Shang Z. Identification and validation of an EMT-related LncRNA signature for HNSCC to predict survival and immune landscapes. Front Cell Dev Biol. 2021;9:798898. https://doi.org/10.3389/fcell.2021.798898.CrossRefPubMed

25.

Zhao H, Wang F, Wang X, Zhao X, Ji J. HPV-related prognostic signature predicts survival in head and neck squamous cell carcinoma. J Oncol. 2022;2022:7357566. https://doi.org/10.1155/2022/7357566.CrossRefPubMedPubMedCentral

26.

Jiang X, Ke J, Jia L, An X, Ma H, Li Z, Yuan W. A novel cuproptosis-related gene signature of prognosis and immune microenvironment in head and neck squamous cell carcinoma cancer. J Cancer Res Clin Oncol. 2023;149:203–18. https://doi.org/10.1007/s00432-022-04471-7.CrossRefPubMed

27.

McDermott JD, Bowles DW. Epidemiology of head and neck squamous cell carcinomas: impact on staging and prevention strategies. Curr Treat Options Oncol. 2019;20:43. https://doi.org/10.1007/s11864-019-0650-5.CrossRefPubMed

28.

Ebrahimi A, Luk PP, Low H, McDowell L, Magarey M, Smith PN, Perriman DM, Veness M, Gupta R, Clark JR. A critical analysis of the 8^th edition TNM staging for head and neck cutaneous squamous cell carcinoma with lymph node metastases and comparison to N1S3 stage and ITEM risk score: a multicenter study. J Surg Oncol. 2021;123:1531–9. https://doi.org/10.1002/jso.26410.CrossRefPubMed

29.

Liao Y, Li P, Wang Y, Chen H, Ning S, Su D. Construction of asthma related competing endogenous RNA network revealed novel long non-coding RNAs and potential new drugs. Respir Res. 2020;21:14. https://doi.org/10.1186/s12931-019-1257-x.CrossRefPubMedPubMedCentral

30.

Zhuang Q, Jin Z, Zheng X, Jin T, Xiang L. Long non-coding RNA LINC00460 serves as a potential biomarker and oncogene via regulation of the miR-320b/PBX3 axis in acute myeloid leukemia. Mol Med Rep. 2021;23:435. https://doi.org/10.3892/mmr.2021.12074.CrossRefPubMedPubMedCentral

31.

Goodman AM, Kato S, Bazhenova L, Patel SP, Frampton GM, Miller V, Stephens PJ, Daniels GA, Kurzrock R. Tumor mutational burden as an independent predictor of response to immunotherapy in diverse cancers. Mol Cancer Ther. 2017;16:2598–608. https://doi.org/10.1158/1535-7163.MCT-17-0386.CrossRefPubMedPubMedCentral

32.

Yang H, Yu M, Zhong S, You Y, Feng F. Neoantigens and the tumor microenvironment play important roles in the prognosis of high-grade serous ovarian cancer. J Ovarian Res. 2022;15:18. https://doi.org/10.1186/s13048-022-00955-9.CrossRefPubMedPubMedCentral

33.

Yang B, Shen J, Xu L, Chen Y, Che X, Qu X, Liu Y, Teng Y, Li Z. Genome-wide identification of a novel eight-lncRNA signature to improve prognostic prediction in head and neck squamous cell carcinoma. Front Oncol. 2019;9:898. https://doi.org/10.3389/fonc.2019.00898.CrossRefPubMedPubMedCentral

34.

Zhang L, Li B, Peng Y, Wu F, Li Q, Lin Z, Xie S, Xiao L, Lin X, Ou Z, Cai T, Rong H, Fan S, Li J. The prognostic value of TMB and the relationship between TMB and immune infiltration in head and neck squamous cell carcinoma: a gene expression-based study. Oral Oncol. 2020;110:104943. https://doi.org/10.1016/j.oraloncology.2020.104943.CrossRefPubMed

35.

Zhang G, Xu Z, Wang N. Network of microRNA, transcription factors, target genes and host genes in human mesothelioma. Exp Ther Med. 2017;13:3039–46. https://doi.org/10.3892/etm.2017.4296.CrossRefPubMedPubMedCentralADS

36.

Lyu H, Li M, Jiang Z, Liu Z, Wang X. Correlate the TP53 mutation and the HRAS mutation with immune signatures in head and neck squamous cell cancer. Comput Struct Biotechnol J. 2019;17:1020–30. https://doi.org/10.1016/j.csbj.2019.07.009.CrossRefPubMedPubMedCentral

37.

Basyuni S, Nugent G, Ferro A, Barker E, Reddin I, Jones O, Lechner M, O’Leary B, Jones T, Masterson L, Fenton T, Schache A. Value of p53 sequencing in the prognostication of head and neck cancer: a systematic review and meta-analysis. Sci Rep. 2022;12:20776. https://doi.org/10.1038/s41598-022-25291-2.CrossRefPubMedPubMedCentralADS

38.

Xie H, Ruan G, Zhang Q, Ge Y, Song M, Zhang X, Liu X, Lin S, Zhang X, Li X, Zhang K, Yang M, Tang M, Cong M, Shi H. Combination of nutritional risk index and handgrip strength on the survival of patients with cancer cachexia: a multi- center cohort study. J Inflamm Res. 2022;15:1005–15. https://doi.org/10.2147/JIR.S352250.CrossRefPubMedPubMedCentral

39.

Zhang Z, Gao W, Tan X, Deng T, Zhou W, Jian H, Zeng P. Construction and verification of a novel circadian clock related long non-coding RNA model and prediction of treatment for survival prognosis in patients with hepatocellular carcinoma. BMC Cancer. 2023;23:57. https://doi.org/10.1186/s12885-023-10508-y.CrossRefPubMedPubMedCentral

40.

Liu C, Zhou X, Zeng H, Wu D, Liu L. HILPDA is a prognostic biomarker and correlates with macrophage infiltration in pan-cancer. Front Oncol. 2021;11:597860. https://doi.org/10.3389/fonc.2021.597860.CrossRefPubMedPubMedCentral

41.

Wang K, Guan C, Yu J, Chen X, Shang X, Mei S, Feng X, Zheng L. Systematic pan-cancer analysis and experimental verification identify FOXA1 as an immunological and prognostic biomarker in epithelial ovarian cancer. Dis Markers. 2022;2022:9328972. https://doi.org/10.1155/2022/9328972.CrossRefPubMedPubMedCentral

42.

Cui W, Wang Y, Guo J, Zhang Z. Construction of a cuproptosis-associated long non-coding RNA risk prediction model for pancreatic adenocarcinoma based on the TCGA database. Medicine. 2023;102: e32808. https://doi.org/10.1097/MD.0000000000032808.CrossRefPubMedPubMedCentral

43.

Han QL, Cui Z, Wang Q, Pang F, Li D, Wang D. Upregulation of OTX2-AS1 is associated with immune infiltration and predicts prognosis of gastric cancer. Technol Cancer Res Treat. 2023;22:15330338231154092. https://doi.org/10.1177/15330338231154091.CrossRefPubMedPubMedCentral

44.

Huang D, Guo W, Gao J, Chen J, Olatunji JO. Clinacanthus nutans (Burm. f.) lindau ethanol extract inhibits hepatoma in mice through upregulation of the immune response. Molecules. 2015;20:17405–28. https://doi.org/10.3390/molecules200917405.CrossRefPubMedPubMedCentral

45.

Li Z, Chen G, Cai Z, Dong X, Qiu L, Xu H, Zeng Y, Liu X, Liu J. Genomic and transcriptional Profiling of tumor infiltrated CD8(+) T cells revealed functional heterogeneity of antitumor immunity in hepatocellular carcinoma. Oncoimmunology. 2019;8: e1538436. https://doi.org/10.1080/2162402X.2018.1538436.CrossRefPubMed

46.

Mikuła T, Suchacz M, Sapuła M, Wiercińska-Drapało A. Significance of vascular cell adhesion molecule-1 and tumor necrosis factor-alpha in HIV-infected patients. J Clin Med. 2022;11:514. https://doi.org/10.3390/jcm11030514.CrossRefPubMedPubMedCentral

47.

Xu Y, Hong M, Kong D, Deng J, Zhong Z, Liang J. Ferroptosis-associated DNA methylation signature predicts overall survival in patients with head and neck squamous cell carcinoma. BMC Genomics. 2022;23:63. https://doi.org/10.1186/s12864-022-08296-z.CrossRefPubMedPubMedCentral

48.

Rodriguez-Garcia A, Lynn RC, Poussin M, Eiva MA, Shaw LC, O’Connor RS, Minutolo NG, Casado-Medrano V, Lopez G, Matsuyama T, Powell DJ Jr. CAR-T cell-mediated depletion of immunosuppressive tumor-associated macrophages promotes endogenous antitumor immunity and augments adoptive immunotherapy. Nat Commun. 2021;12:877. https://doi.org/10.1038/s41467-021-20893-2.CrossRefPubMedPubMedCentralADS

49.

Saud SM, Li W, Morris NL, Matter MS, Colburn NH, Kim YS, Young MR. Resveratrol prevents tumorigenesis in mouse model of Kras activated sporadic colorectal cancer by suppressing oncogenic Kras expression. Carcinogenesis. 2014;35:2778–86. https://doi.org/10.1093/carcin/bgu209.CrossRefPubMedPubMedCentral

50.

Wu Z, Wang M, Liu Q, Liu Y, Zhu K, Chen L, Guo H, Li Y, Shi B. Identification of gene expression profiles and immune cell infiltration signatures between low and high tumor mutation burden groups in bladder cancer. Int J Med Sci. 2020;17:89–96. https://doi.org/10.7150/ijms.39056.CrossRefPubMedPubMedCentral

51.

Liu Z, Zhang D, Liu C, Li G, Chen H, Ling H, Zhang F, Huang D, Wang X, Liu Y, Zhang X. Comprehensive analysis of myeloid signature genes in head and neck squamous cell carcinoma to predict the prognosis and immune infiltration. Front Immunol. 2021;12:659184. https://doi.org/10.3389/fimmu.2021.659184.CrossRefPubMedPubMedCentral

Title: Identification of a disulfidptosis-related lncRNA signature for the prognostic and immune landscape prediction in head and neck squamous cell carcinoma
Authors: Zhengyu Wei
Chongchang Zhou
Yi Fang
Hongxia Deng
Zhisen Shen
Publication date: 01-12-2024
Publisher: Springer US
Published in: Discover Oncology / Issue 1/2024
Print ISSN: 1868-8497
Electronic ISSN: 2730-6011
DOI: https://doi.org/10.1007/s12672-024-00932-2

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

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.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits

Illustration of figure on mountain summit/© Orapun / Stock.adobe.com, STEP AAG HeroTeaserCollection image/© Tarek / Generated with AI / Stock.adobe.com, ACC 2024 Pediatric and Congenital Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Pulmonary Vascular Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Valvular Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 HF and Cardiomyopathies: Year in Review/© 2024 American College of Cardiology, Woman out walking/© Seventyfour / stock.adobe.com (symbolic image with model), Woman checking smartwatch /© saltdium / stock.adobe.com (symbolic image with model), Cardiac catheterization/© Damian / stock.adobe.com

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2024

DSCAM-AS1 promotes the development of prostate cancer

MAP3K4 kinase action and dual role in cancer

Role of long non-coding RNA ELFN1-AS1 in carcinogenesis

GALNT2 targeted by miR-139-5p promotes proliferation of clear cell renal cell carcinoma via inhibition of LATS2 activation

FAM83D acts as an oncogene by regulating cell cycle progression via multiple pathways in synovial sarcoma: a potential novel downstream target oncogene of anlotinib

The role of tumor parenchyma and brain cortex signal intensity ratio in differentiating solitary fibrous tumors and meningiomas

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

Highlights from the ACC 2024 Congress

ACC 2024 Congress Coverage