Screening of Immune-related lncRNAs in Lung Adenocarcinoma and Establishing a Survival Prognostic Risk Prediction Model


Cite item

Full Text

Abstract

Objective:This study aimed to improve lung adenocarcinoma (LUAD) prognosis prediction based on a signature of immune-related long non-coding RNAs (lncRNAs).

Methods:LUAD samples from the TCGA database were divided into the immunity_H group and the immunity_L group. Differentially expressed RNAs (DERs) between the two groups were identified. Optimized immune-related lncRNAs combination was obtained using LASSO Cox regression. A prognostic risk prediction (RS) model was built and further validated in the training and validation datasets. A network among lncRNAs in the RS model, their co-expressed DERs, and the related KEGG pathways were established. Critical lncRNAs were validated in LUAD tissue samples.

Results:In total, 255 DERs were obtained, and 11 immune-related lncRNAs were significantly related to prognosis. Six lncRNAs were demonstrated as an optimal combination for building the RS model, including LINC00944, LINC00930, LINC00607, LINC00582, LINC00543, and LINC00319. The KM curve and ROC curve revealed the RS model to be a reliable indicator for LUAD prognosis. LINC00944 and LINC00582 showed a co-expression relationship with the MS4A1. LINC00944, LINC00582, and MS4A1 were successfully validated in LUAD samples.

Conclusion:We have established a promising LUAD patient survival prediction model based on six immune-related lncRNAs. For LUAD patients, this prognostic model could guide personalized treatment.

About the authors

Wenxia Jiang

School of Clinical Medicine, Shanghai University of Medicine and Health Sciences

Author for correspondence.
Email: info@benthamscience.net

Xuyou Zhu

Department of Pathology, Tongji Hospital of Tongji University

Email: info@benthamscience.net

Jiaqi Bo

Department of Pathology, Tongji Hospital of Tongji University

Email: info@benthamscience.net

Jun Ma

Department of Nephrology, ing’an District Center Hospital of Shanghai, Fudan University

Author for correspondence.
Email: info@benthamscience.net

References

  1. Thandra, K.C.; Barsouk, A.; Saginala, K.; Sukumar Aluru, J.; Barsouk, A. Epidemiology of lung cancer. Contemp. Oncol., 2021, 25(1), 45-52. doi: 10.5114/wo.2021.103829 PMID: 33911981
  2. Rasheed, Z. Why is cancer becoming a global endemic today? Int. J. Health Sci., 2020, 14(5), 1-2. PMID: 32952499
  3. Liu, J.; Cho, S.N.; Akkanti, B.; Jin, N.; Mao, J.; Long, W.; Chen, T.; Zhang, Y.; Tang, X.; Wistub, I.I.; Creighton, C.J.; Kheradmand, F.; DeMayo, F.J. ErbB2 pathway activation upon Smad4 loss promotes lung tumor growth and metastasis. Cell Rep., 2015, 10(9), 1599-1613. doi: 10.1016/j.celrep.2015.02.014 PMID: 25753424
  4. Tong, L.; Liu, J.; Yan, W.; Cao, W.; Shen, S.; Li, K.; Li, L.; Niu, G. RDM1 plays an oncogenic role in human lung adenocarcinoma cells. Sci. Rep., 2018, 8(1), 11525. doi: 10.1038/s41598-018-30071-y PMID: 30069034
  5. Succony, L.; Rassl, D.M.; Barker, A.P.; McCaughan, F.M.; Rintoul, R.C. Adenocarcinoma spectrum lesions of the lung: Detection, pathology and treatment strategies. Cancer Treat. Rev., 2021, 99, 102237. doi: 10.1016/j.ctrv.2021.102237 PMID: 34182217
  6. Zhou, Y.; Tang, L.; Chen, Y.; Zhang, Y.; Zhuang, W. An immune panel signature predicts prognosis of lung adenocarcinoma patients and correlates with immune microenvironment. Front. Cell Dev. Biol., 2021, 9, 797984. doi: 10.3389/fcell.2021.797984 PMID: 34993203
  7. Chen, D.; Wang, Y.; Zhang, X.; Ding, Q.; Wang, X.; Xue, Y.; Wang, W.; Mao, Y.; Chen, C.; Chen, Y. Characterization of tumor microenvironment in lung adenocarcinoma identifies immune signatures to predict clinical outcomes and therapeutic responses. Front. Oncol., 2021, 11, 581030. doi: 10.3389/fonc.2021.581030 PMID: 33747907
  8. Zhang, L.; Xu, X.; Su, X. Noncoding RNAs in cancer immunity: Functions, regulatory mechanisms, and clinical application. Mol. Cancer, 2020, 19(1), 48. doi: 10.1186/s12943-020-01154-0 PMID: 32122338
  9. Notarte, K.I.; Senanayake, S.; Macaranas, I.; Albano, P.M.; Mundo, L.; Fennell, E.; Leoncini, L.; Murray, P. MicroRNA and other non-coding RNAs in epstein–barr virus-associated cancers. Cancers, 2021, 13(15), 3909. doi: 10.3390/cancers13153909 PMID: 34359809
  10. Li, J.; Zhang, C.; Zhang, C.; Wang, H. Construction of immune-related and prognostic lncRNA clusters and identification of their immune and genomic alterations characteristics in lung adenocarcinoma samples. Aging, 2020, 12(10), 9868-9881. doi: 10.18632/aging.103251 PMID: 32445554
  11. Yu, L.; Qiao, R.; Xu, J.; Han, B.; Zhong, R. FAM207BP, a pseudogene-derived lncRNA, facilitates proliferation, migration and invasion of lung adenocarcinoma cells and acts as an immune-related prognostic factor. Life Sci., 2021, 268, 119022. doi: 10.1016/j.lfs.2021.119022 PMID: 33434533
  12. Zhao, S.; Jin, X.; Xu, S. Expression of RASGRP2 in lung adenocarcinoma and its effect on immune microenvironment. Zhongguo Fei Ai Za Zhi, 2021, 24(6), 404-411. PMID: 34157800
  13. Edgar, R.; Domrachev, M.; Lash, A.E. Gene expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res., 2002, 30(1), 207-210. doi: 10.1093/nar/30.1.207 PMID: 11752295
  14. Der, S.D.; Sykes, J.; Pintilie, M.; Zhu, C.Q.; Strumpf, D.; Liu, N.; Jurisica, I.; Shepherd, F.A.; Tsao, M.S. Validation of a histology-independent prognostic gene signature for early-stage, non-small-cell lung cancer including stage IA patients. J. Thorac. Oncol., 2014, 9(1), 59-64. doi: 10.1097/JTO.0000000000000042 PMID: 24305008
  15. Botling, J.; Edlund, K.; Lohr, M.; Hellwig, B.; Holmberg, L.; Lambe, M.; Berglund, A.; Ekman, S.; Bergqvist, M.; Pontén, F.; König, A.; Fernandes, O.; Karlsson, M.; Helenius, G.; Karlsson, C.; Rahnenführer, J.; Hengstler, J.G.; Micke, P. Biomarker discovery in non-small cell lung cancer: Integrating gene expression profiling, meta-analysis, and tissue microarray validation. Clin. Cancer Res., 2013, 19(1), 194-204. doi: 10.1158/1078-0432.CCR-12-1139 PMID: 23032747
  16. Jabs, V.; Edlund, K.; König, H.; Grinberg, M.; Madjar, K.; Rahnenführer, J.; Ekman, S.; Bergkvist, M.; Holmberg, L.; Ickstadt, K.; Botling, J.; Hengstler, J.G.; Micke, P. Integrative analysis of genome-wide gene copy number changes and gene expression in non-small cell lung cancer. PLoS One, 2017, 12(11), e0187246. doi: 10.1371/journal.pone.0187246 PMID: 29112949
  17. Lohr, M.; Hellwig, B.; Edlund, K.; Mattsson, J.S.M.; Botling, J.; Schmidt, M.; Hengstler, J.G.; Micke, P.; Rahnenführer, J. Identification of sample annotation errors in gene expression datasets. Arch. Toxicol., 2015, 89(12), 2265-2272. doi: 10.1007/s00204-015-1632-4 PMID: 26608184
  18. Li, B.L.; Wan, X.P. Prognostic significance of immune landscape in tumour microenvironment of endometrial cancer. J. Cell. Mol. Med., 2020, 24(14), 7767-7777. doi: 10.1111/jcmm.15408 PMID: 32424934
  19. Hu, D.; Zhou, M.; Zhu, X. Deciphering immune-associated genes to predict survival in clear cell renal cell cancer. BioMed Res. Int., 2019, 2019, 1-10. doi: 10.1155/2019/2506843 PMID: 31886185
  20. Ritchie, M.E.; Phipson, B.; Wu, D.; Hu, Y.; Law, C.W.; Shi, W.; Smyth, G.K. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res., 2015, 43(7), e47. doi: 10.1093/nar/gkv007 PMID: 25605792
  21. Huang, D.W.; Sherman, B.T.; Lempicki, R.A. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protoc., 2009, 4(1), 44-57. doi: 10.1038/nprot.2008.211 PMID: 19131956
  22. Huang, D.W.; Sherman, B.T.; Lempicki, R.A. Bioinformatics enrichment tools: Paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res., 2009, 37(1), 1-13. doi: 10.1093/nar/gkn923 PMID: 19033363
  23. Wang, P.; Wang, Y.; Hang, B.; Zou, X.; Mao, J.H. A novel gene expression-based prognostic scoring system to predict survival in gastric cancer. Oncotarget, 2016, 7(34), 55343-55351. doi: 10.18632/oncotarget.10533 PMID: 27419373
  24. Tibshirani, R. The lasso method for variable selection in the Cox model. Stat. Med., 1997, 16(4), 385-395. doi: 10.1002/(SICI)1097-0258(19970228)16:43.0.CO;2-3 PMID: 9044528
  25. Goeman, J.J. L1 penalized estimation in the Cox proportional hazards model. Biom. J., 2010, 52(1), 70-84. PMID: 19937997
  26. Liu, X.F.; Gao, Z.M.; Wang, R.Y.; Wang, P.L.; Li, K.; Gao, S. Comparison of Billroth I, Billroth II, and Roux-en-Y reconstructions after distal gastrectomy according to functional recovery: A meta-analysis. Eur. Rev. Med. Pharmacol. Sci., 2019, 23(17), 7532-7542. PMID: 31539143
  27. Yu, G.; Wang, L.G.; Han, Y.; He, Q.Y. clusterProfiler: An R package for comparing biological themes among gene clusters. OMICS, 2012, 16(5), 284-287. doi: 10.1089/omi.2011.0118 PMID: 22455463
  28. Xu, Q.; Xu, H.; Deng, R.; Wang, Z.; Li, N.; Qi, Z.; Zhao, J.; Huang, W. Multi-omics analysis reveals prognostic value of tumor mutation burden in hepatocellular carcinoma. Cancer Cell Int., 2021, 21(1), 342. doi: 10.1186/s12935-021-02049-w PMID: 34217320
  29. Shannon, P.; Markiel, A.; Ozier, O.; Baliga, N.S.; Wang, J.T.; Ramage, D.; Amin, N.; Schwikowski, B.; Ideker, T. Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Res., 2003, 13(11), 2498-2504. doi: 10.1101/gr.1239303 PMID: 14597658
  30. Grondin, C.J.; Davis, A.P.; Wiegers, J.A.; Wiegers, T.C.; Sciaky, D.; Johnson, R.J.; Mattingly, C.J. Predicting molecular mechanisms, pathways, and health outcomes induced by Juul e-cigarette aerosol chemicals using the Comparative Toxicogenomics Database. Curr. Res. Toxicol., 2021, 2, 272-281. doi: 10.1016/j.crtox.2021.08.001 PMID: 34458863
  31. Mouliere, F.; Chandrananda, D.; Piskorz, A.M.; Moore, E.K.; Morris, J.; Ahlborn, L.B.; Mair, R.; Goranova, T.; Marass, F.; Heider, K.; Wan, J.C.M.; Supernat, A.; Hudecova, I.; Gounaris, I.; Ros, S.; Jimenez-Linan, M.; Garcia-Corbacho, J.; Patel, K.; Østrup, O.; Murphy, S.; Eldridge, M.D.; Gale, D.; Stewart, G.D.; Burge, J.; Cooper, W.N.; van der Heijden, M.S.; Massie, C.E.; Watts, C.; Corrie, P.; Pacey, S.; Brindle, K.M.; Baird, R.D.; Mau-Sørensen, M.; Parkinson, C.A.; Smith, C.G.; Brenton, J.D.; Rosenfeld, N. Enhanced detection of circulating tumor DNA by fragment size analysis. Sci. Transl. Med., 2018, 10(466), eaat4921. doi: 10.1126/scitranslmed.aat4921 PMID: 30404863
  32. Dang, D.K.; Park, B.H. Circulating tumor DNA: Current challenges for clinical utility. J. Clin. Invest., 2022, 132(12), e154941. doi: 10.1172/JCI154941 PMID: 35703177
  33. Campos-Carrillo, A.; Weitzel, J.N.; Sahoo, P.; Rockne, R.; Mokhnatkin, J.V.; Murtaza, M.; Gray, S.W.; Goetz, L.; Goel, A.; Schork, N.; Slavin, T.P. Circulating tumor DNA as an early cancer detection tool. Pharmacol. Ther., 2020, 207, 107458. doi: 10.1016/j.pharmthera.2019.107458 PMID: 31863816
  34. Beylerli, O.; Gareev, I.; Sufianov, A.; Ilyasova, T.; Guang, Y. Long noncoding RNAs as promising biomarkers in cancer. Noncoding RNA Res., 2022, 7(2), 66-70. doi: 10.1016/j.ncrna.2022.02.004 PMID: 35310927
  35. Li, Y.; Shen, R.; Wang, A.; Zhao, J.; Zhou, J.; Zhang, W.; Zhang, R.; Zhu, J.; Liu, Z.; Huang, J. Construction of a prognostic immune-related LncRNA risk model for lung adenocarcinoma. Front. Cell Dev. Biol., 2021, 9, 648806. doi: 10.3389/fcell.2021.648806 PMID: 33869203
  36. Wang, J.; Yin, X.; Zhang, Y.Q.; Ji, X. Identification and validation of a novel immune-related four-lncRNA signature for lung adenocarcinoma. Front. Genet., 2021, 12, 639254. doi: 10.3389/fgene.2021.639254 PMID: 33708243
  37. Mohebi, M.; Ghafouri-Fard, S.; Modarressi, M.H.; Dashti, S.; Zekri, A.; Kholghi-Oskooei, V.; Taheri, M. Expression analysis of vimentin and the related lncRNA network in breast cancer. Exp. Mol. Pathol., 2020, 115, 104439. doi: 10.1016/j.yexmp.2020.104439 PMID: 32283061
  38. Shen, Y.; Peng, X.; Shen, C. Identification and validation of immune-related lncRNA prognostic signature for breast cancer. Genomics, 2020, 112(3), 2640-2646. doi: 10.1016/j.ygeno.2020.02.015 PMID: 32087243
  39. Xue, Q.; Wang, Y.; Zheng, Q.; Chen, L.; Jin, Y.; Shen, X.; Li, Y. Construction of a prognostic immune-related lncRNA model and identification of the immune microenvironment in middle- or advanced-stage lung squamous carcinoma patients. Heliyon, 2022, 8(5), e09521. doi: 10.1016/j.heliyon.2022.e09521 PMID: 35663751
  40. He, B.; Pan, H.; Zheng, F.; Chen, S.; Bie, Q.; Cao, J.; Zhao, R.; Liang, J.; Wei, L.; Zeng, J.; Li, H.; Cui, X.; Ding, Y.; Chao, W.; Xiang, T.; Cheng, Y.; Qiu, G.; Huang, S.; Tang, L.; Chang, J.; Luo, D.; Yang, J.; Zhang, B. Long noncoding RNA LINC00930 promotes PFKFB3-mediated tumor glycolysis and cell proliferation in nasopharyngeal carcinoma. J. Exp. Clin. Cancer Res., 2022, 41(1), 77. doi: 10.1186/s13046-022-02282-9 PMID: 35209949
  41. Zhang, L.; Liu, H.; Long, Y.; Zhang, Y. Overexpression of LINC00607 inhibits cell growth and aggressiveness by regulating the miR-1289/EFNA5 axis in non-small-cell lung cancer. Open Med., 2023, 18(1), 20230649. doi: 10.1515/med-2023-0649 PMID: 37333453
  42. Gong, W.; Hong, L.; Qian, Y. Identification and experimental validation of LINC00582 Associated with B Cell immune and development of pulpitis: Bioinformatics and in vitro analysis. Diagnostics, 2023, 13(10), 1678.
  43. Qi, G.; Kong, W.; Mou, X.; Wang, S. A new method for excavating feature lncRNA in lung adenocarcinoma based on pathway crosstalk analysis. J. Cell. Biochem., 2019, 120(6), 9034-9046. doi: 10.1002/jcb.28177 PMID: 30582215
  44. Ji, X.; Bossé, Y.; Landi, M.T.; Gui, J.; Xiao, X.; Qian, D.; Joubert, P.; Lamontagne, M.; Li, Y.; Gorlov, I.; de Biasi, M.; Han, Y.; Gorlova, O.; Hung, R.J.; Wu, X.; McKay, J.; Zong, X.; Carreras-Torres, R.; Christiani, D.C.; Caporaso, N.; Johansson, M.; Liu, G.; Bojesen, S.E.; Le Marchand, L.; Albanes, D.; Bickeböller, H.; Aldrich, M.C.; Bush, W.S.; Tardon, A.; Rennert, G.; Chen, C.; Teare, M.D.; Field, J.K.; Kiemeney, L.A.; Lazarus, P.; Haugen, A.; Lam, S.; Schabath, M.B.; Andrew, A.S.; Shen, H.; Hong, Y.C.; Yuan, J.M.; Bertazzi, P.A.; Pesatori, A.C.; Ye, Y.; Diao, N.; Su, L.; Zhang, R.; Brhane, Y.; Leighl, N.; Johansen, J.S.; Mellemgaard, A.; Saliba, W.; Haiman, C.; Wilkens, L.; Fernandez-Somoano, A.; Fernandez-Tardon, G.; van der Heijden, E.H.F.M.; Kim, J.H.; Dai, J.; Hu, Z.; Davies, M.P.A.; Marcus, M.W.; Brunnström, H.; Manjer, J.; Melander, O.; Muller, D.C.; Overvad, K.; Trichopoulou, A.; Tumino, R.; Doherty, J.; Goodman, G.E.; Cox, A.; Taylor, F.; Woll, P.; Brüske, I.; Manz, J.; Muley, T.; Risch, A.; Rosenberger, A.; Grankvist, K.; Johansson, M.; Shepherd, F.; Tsao, M.S.; Arnold, S.M.; Haura, E.B.; Bolca, C.; Holcatova, I.; Janout, V.; Kontic, M.; Lissowska, J.; Mukeria, A.; Ognjanovic, S.; Orlowski, T.M.; Scelo, G.; Swiatkowska, B.; Zaridze, D.; Bakke, P.; Skaug, V.; Zienolddiny, S.; Duell, E.J.; Butler, L.M.; Koh, W.P.; Gao, Y.T.; Houlston, R.; McLaughlin, J.; Stevens, V.; Nickle, D.C.; Obeidat, M.; Timens, W.; Zhu, B.; Song, L.; Artigas, M.S.; Tobin, M.D.; Wain, L.V.; Gu, F.; Byun, J.; Kamal, A.; Zhu, D.; Tyndale, R.F.; Wei, W.Q.; Chanock, S.; Brennan, P.; Amos, C.I. Identification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk. Nat. Commun., 2018, 9(1), 3221. doi: 10.1038/s41467-018-05074-y PMID: 30104567
  45. Zhou, W.; Yin, M.; Cui, H.; Wang, N.; Zhao, L.L.; Yuan, L.Z.; Yang, X.P.; Ding, X.M.; Men, F.Z.; Ma, X.; Na, J.R. Identification of potential therapeutic target genes and mechanisms in non-small-cell lung carcinoma in non-smoking women based on bioinformatics analysis. Eur. Rev. Med. Pharmacol. Sci., 2015, 19(18), 3375-3384. PMID: 26439031
  46. Bousoik, E.; Montazeri Aliabadi, H. "Do We Know Jack" About JAK? A Closer Look at JAK/STAT Signaling Pathway. Front. Oncol., 2018, 8, 287. doi: 10.3389/fonc.2018.00287 PMID: 30109213
  47. Templeton, A.K.; Miyamoto, S.; Babu, A.; Munshi, A.; Ramesh, R. Cancer stem cells: Progress and challenges in lung cancer. Stem Cell Investig., 2014, 1, 9. PMID: 27358855
  48. Mudd, T.W., Jr; Lu, C.; Klement, J.D.; Liu, K. MS4A1 expression and function in T cells in the colorectal cancer tumor microenvironment. Cell. Immunol., 2021, 360, 104260. doi: 10.1016/j.cellimm.2020.104260 PMID: 33352466

Supplementary files

Supplementary Files
Action
1. JATS XML

Copyright (c) 2024 Bentham Science Publishers