IJCEMR

Article http://dx.doi.org/10.26855/ijcemr.2024.01.030

Disulfidptosis-related lncRNAs Predict Prognosis and Immune Landscape in Endometrial Cancer

TOTAL VIEWS: 686

Yu Zhang1, Yaping Wang1,2, Xiabing Li1, Qimin Jin1, Hongjian Zhang1, Hai Zhu1, Qing Liu1, Hongyu Li1,2,*

1Gynecologic Oncology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

2Zhengzhou Key Laboratory of Gynecological Oncology, Zhengzhou, Henan, China.

*Corresponding author: Hongyu Li

Published: March 12,2024

Abstract

Background: Recently, a novel form of cell death called disulfidptosis was identified. It is characterized by rapid cell death caused by disulfide stress resulting from excessive cystine accumulation within cells. Disulfidptosis holds promise as a potential target for intervention in tumor treatment. However, the roles and prognostic value of disulfidptosis-related lncRNAs (DRLs) in EC remain largely unknown. Therefore, the objective of this study is to develop a prediction model based on DRLs to forecast the prognosis and assess the immunotherapy response in EC patients, as well as identify potential chemotherapy drugs for treatment. Methods: We constructed a model by screening DRLs associated with EC prognosis through bioinformatics methods and validated it. Furthermore, enrichment analysis was conducted to explore functional differences between different risk populations. Additionally, we examined the associations between the risk score and tumor mutational burden (TMB), tumor microenvironment (TME), tumor immune dysfunction and exclusion (TIDE), and drug sensitivity. Finally, we validated this using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Results: We identified 8 DRLs (Z69733.1, AL158071.4, AC022960.1 AC005034.2, AC003086.1, AC024230.1, AL499602.1, RAB11B-AS1) and constructed a robust risk model. Further analysis revealed that the low-risk group had superior overall survival (OS), immunotherapy response, and drug sensitivity compared to the high-risk group. Conclusion: Our risk model provides an accurate prediction of prognosis and immunotherapy response in EC patients, offering significant clinical implications and novel insights for clinicians in the treatment of EC.

References

[1] Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal. GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Ca Cancer J Clin., 2018, 68(6):394-424.

[2] Makker V, MacKay H, Ray-Coquard I, Levine DA, Westin SN, Aoki D, Oaknin A. Endometrial cancer. Nature Reviews Disease Primers, 2021, 7(1):88.

[3] Brooks RA, Fleming GF, Lastra RR, Lee NK, Moroney JW, Son CH, Tatebe K, Veneris JL. Current recommendations and recent progress in endometrial cancer. CA: A Cancer Journal for Clinicians, 2019, 69(4):258-279.

[4] Tang D, Kang R, Berghe TV, Vandenabeele P, Kroemer G. The molecular machinery of regulated cell death. Cell Research, 2019, 29(5):347-364.

[5] Edoui S, Herold MJ, Strasser A. Emerging connectivity of programmed cell death pathways and its physiological implications. Nature Reviews Molecular Cell Biology, 2020, 21(11):678-695.

[6] Tsvetkov P, Coy S, Petrova B, Dreishpoon M, Verma A, Abdusamad M, Rossen J, Joesch-Cohen L, Humeidi R, Spangler RD. Copper induces cell death by targeting lipoylated TCA cycle proteins. Science, 2022, 375(6586):1254-1261.

[7] Liu X, Nie L, Zhang Y, Yan Y, Wang C, Colic M, Olszewski K, Horbath A, Chen X, Lei G. Actin cytoskeleton vulnerability to disulfide stress mediates disulfidptosis. Nature Cell Biology, 2023, 25(3):404-414.

[8] Liu X, Olszewski K, Zhang Y, Lim EW, Shi J, Zhang X, Zhang J, Lee H, Koppula P, Lei G. Cystine transporter regulation of pentose phosphate pathway dependency and disulfide stress exposes a targetable metabolic vulnerability in cancer. Nature Cell Biology, 2020, 22(4):476-486.

[9] Zheng P, Zhou C, Ding Y, Duan S. Disulfidptosis: a new target for metabolic cancer therapy. Journal of Experimental & Clinical Cancer Research, 2023, 42(1):103.

[10] Zhong Z, Zhang C, Ni S, Ma M, Zhang X, Sang W, Lv T, Qian Z, Yi C, Yu B. NFATc1-mediated expression of SLC7A11 drives sensitivity to TXNRD1 inhibitors in osteoclast precursors. Redox Biology, 2023, 63:102711.

[11] Atianand MK, Caffrey DR, Fitzgerald KA. Immunobiology of long noncoding RNAs. Annual Review of Immunology, 2017, 35:177-198.

[12] Cech TR, Steitz JA. The noncoding RNA revolution—Trashing Old Rules to Forge New Ones. Cell, 2014, 157(1):77-94.

[13] Guttman M, Russell P, Ingolia NT, Weissman JS, Lander ES. Ribosome profiling provides evidence that large noncoding RNAs do not encode proteins. Cell, 2013, 154(1):240-251.

[14] Moran VA, Perera RJ, Khalil AM. Emerging functional and mechanistic paradigms of mammalian long non-coding RNAs. Nucleic Acids Research, 2012, 40(14):6391-6400.

[15] Bhan A, Soleimani M, Mandal SS. Long noncoding RNA and cancer: a new paradigm. Cancer Research, 2017, 77(15):3965-3981.

[16] Fang Y, Fullwood MJ. Roles, functions, and mechanisms of long non-coding RNAs in cancer. Genomics, Proteomics & Bioinformatics, 2016, 14(1):42-54.

[17] Chi Y, Wang D, Wang J, Yu W, Yang J. Long non-coding RNA in the pathogenesis of cancers. Cells, 2019, 8(9):1015.

[18] Renhua G, Yue S, Shidai J, Jing F, Xiyi L. 165P: Long noncoding RNA LUCAT1 is associated with poor prognosis in human non-small cell lung cancer and affects cell proliferation via regulating p21 and p57 expression. Journal of Thoracic Oncology 2016, 11(4):S129.

[19] Cao H, Liu Z, Huang P, Yue Y, Xi J. lncRNA-RMRP promotes proliferation, migration and invasion of bladder cancer via miR-206. Eur Rev Med Pharmacol Sci., 2019, 23(3):1012-1021.

[20] Dai Y-z, Liu Y-d, Li J, Chen M-t, Huang M, Wang F, Yang Q-s, Yuan J-h, Sun S-h. METTL16 promotes hepatocellular carcinoma progression through downregulating RAB11B-AS1 in an m6A-dependent manner. Cellular & Molecular Biology Letters, 2022, 27(1):41.

[21] Lee YC, Lheureux S, Oza AM. Treatment strategies for endometrial cancer: current practice and perspective. Current Opinion in Obstetrics and Gynecology, 2017, 29(1):47-58.

[22] Braun MM, Overbeek-Wager E, Grumbo RJ. Diagnosis and management of endometrial cancer. American Family Physician, 2016, 93(6):468-474.

[23] Sideris S, Aoun F, Zanaty M, Martinez NC, Latifyan S, Awada A, Gil T. Efficacy of weekly paclitaxel treatment as a single agent chemotherapy following first-line cisplatin treatment in urothelial bladder cancer. Molecular and Clinical Oncology, 2016, 4(6):1063-1067.

[24] Mitin T, Hunt D, Shipley WU, Kaufman DS, Uzzo R, Wu C-L, Buyyounouski MK, Sandler H, Zietman AL. Transurethral surgery and twice-daily radiation plus paclitaxel-cisplatin or fluorouracil-cisplatin with selective bladder preservation and adjuvant chemotherapy for patients with muscle invasive bladder cancer (RTOG 0233): a randomised multicentre phase 2 trial. The Lancet Oncology, 2013, 14(9):863-872.

[25] Abdi E, Latifi-Navid S, Latifi-Navid H. LncRNA polymorphisms and breast cancer risk. Pathology-Research and Practice, 2022, 229:153729.

[26] Dong P, Xiong Y, Konno Y, Ihira K, Kobayashi N, Yue J, Watari H. Long non-coding RNA DLEU2 drives EMT and glycolysis in endometrial cancer through HK2 by competitively binding with miR-455 and by modulating the EZH2/miR-181a pathway. Journal of Experimental & Clinical Cancer Research, 2021, 40(1):1-16.

[27] Jiang Y, Qiao Z, Jiang J, Zhang J. LINC00958 promotes endometrial cancer cell proliferation and metastasis by regulating the miR-145-3p/TCF4 axis. The Journal of Gene Medicine, 2021, 23(7):e3345.

[28] Homma Y, Hiragi S, Fukuda M. Rab family of small GTPases: an updated view on their regulation and functions. The FEBS Journal, 2021, 288(1):36-55.

[29] Pfeffer SR: Rab GTPases: master regulators that establish the secretory and endocytic pathways. Molecular Biology of the Cell 2017, 28(6):712-715.

[30] Niu Y, Bao L, Chen Y, Wang C, Luo M, Zhang B, Zhou M, Wang JE, Fang YV, Kumar A. HIF2-Induced Long Noncoding RNA RAB11B-AS1 Promotes Hypoxia-Mediated Angiogenesis and Breast Cancer MetastasisRAB11B-AS1 Promotes Angiogenesis and Breast Tumor Metastasis. Cancer Research, 2020, 80(5):964-975.

[31] Sha D, Jin Z, Budczies J, Kluck K, Stenzinger A, Sinicrope FA. Tumor mutational burden as a predictive biomarker in solid tumors. Cancer Discovery, 2020, 10(12):1808-1825.

[32] Yarchoan M, Hopkins A, Jaffee EM. Tumor mutational burden and response rate to PD-1 inhibition. New England Journal of Medicine, 2017, 377(25):2500-2501.

[33] Samstein RM, Lee C-H, Shoushtari AN, Hellmann MD, Shen R, Janjigian YY, Barron DA, Zehir A, Jordan EJ, Omuro A. Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nature Genetics, 2019, 51(2):202-206.

[34] Textor S, Fiegler N, Arnold A, Porgador A, Hofmann TG, Cerwenka A. Human NK Cells Are Alerted to Induction of p53 in Cancer Cells by Upregulation of the NKG2D Ligands ULBP1 and ULBP2ULBP1 and ULBP2 Are Direct p53 Target Genes. Cancer Research, 2011, 71(18):5998-6009.

[35] Dong Z-Y, Zhong W-Z, Zhang X-C, Su J, Xie Z, Liu S-Y, Tu H-Y, Chen H-J, Sun Y-L, Zhou Q. Potential predictive value of TP53 and KRAS mutation status for response to PD-1 blockade immunotherapy in lung adenocarcinoma. Clinical Cancer Research, 2017, 23(12):3012-3024.

How to cite this paper

Disulfidptosis-related lncRNAs Predict Prognosis and Immune Landscape in Endometrial Cancer

How to cite this paper: Yu Zhang, Yaping Wang, Xiabing Li, Qimin Jin, Hongjian Zhang, Hai Zhu, Qing Liu, Hongyu Li. (2024) Disulfidptosis-related lncRNAs Predict Prognosis and Immune Landscape in Endometrial CancerInternational Journal of Clinical and Experimental Medicine Research8(1), 165-179.

DOI: http://dx.doi.org/10.26855/ijcemr.2024.01.030