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Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Research Article

Construction and Validation of an Immune-Related lncRNA Prognosis Model for Thyroid Cancer

Author(s): Zheng Li, Hui Wang, Xia Deng, Jing Zhang, Ling Wang, Wanyan Tang, Wenxin You and Weiqi Nian*

Volume 25, Issue 13, 2022

Published on: 14 April, 2022

Page: [2217 - 2227] Pages: 11

DOI: 10.2174/1386207325666220223123917

Price: $65

Abstract

Background: Immune-related long noncoding RNAs (lncRNAs) play an important role in the development of cancer. This study aimed to identify immune-related lncRNAs in thyroid cancer (THCA) and develop a prognostic model for THCA.

Methods: We downloaded immune-related gene sets from the Gene Set Enrichment Analysis (GSEA) website and obtained THCA gene expression and clinical data from The Cancer Genome Atlas (TCGA) database. Immune-related lncRNAs were then obtained by performing correlation analysis on the expression of lncRNAs and immune-related genes. A prognostic model for THCA immune-related lncRNAs was developed through univariate Cox regression and multiple Cox regression analyses. We confirmed the results in clinical samples using quantitative real-time PCR.

Results: A total of 26 immune-related lncRNAs in THCA were obtained. Then we constructed a prognosis model composed of seven lncRNAs (LINC01614, AC017074.1, LINC01184, LINC00667, ACVR2B-AS1, AC090673.1, and LINC00900). Our model can be used as an independent prognostic factor. Principal component analysis displayed that the lncRNAs in the model can distinguish between high and low-risk groups. Clinical correlation analysis showed that the expression levels of AC090673.1 (P<0.05), LINC01184 (P<0.001), and LINC01614 (P<0.001) were related to disease stage, and LINC00900 (P<0.001) and LINC01614 (P<0.001) were related to T stage. We validated this model in cancer and paracancerous tissues from 24 THCA patients.

Conclusion: We identified and experimentally validated seven immune-related lncRNAs that can serve as potential biomarkers for THCA prognosis.

Keywords: Thyroid cancer, immune, lncRNA, prognosis, biomarker, TCGA.

Graphical Abstract

[1]
Naoum, G.E.; Morkos, M.; Kim, B.; Arafat, W. Novel targeted therapies and immunotherapy for advanced thyroid cancers. Mol. Cancer, 2018, 17(1), 51.
[http://dx.doi.org/10.1186/s12943-018-0786-0] [PMID: 29455653]
[2]
Abdullah, M.I.; Junit, S.M.; Ng, K.L.; Jayapalan, J.J.; Karikalan, B.; Hashim, O.H. Papillary thyroid cancer: Genetic alterations and molecular biomarker investigations. Int. J. Med. Sci., 2019, 16(3), 450-460.
[http://dx.doi.org/10.7150/ijms.29935] [PMID: 30911279]
[3]
Haugen, B.R.; Alexander, E.K.; Bible, K.C.; Doherty, G.M.; Mandel, S.J.; Nikiforov, Y.E.; Pacini, F.; Randolph, G.W.; Sawka, A.M.; Schlumberger, M.; Schuff, K.G.; Sherman, S.I.; Sosa, J.A.; Steward, D.L.; Tuttle, R.M.; Wartofsky, L. 2015 American thyroid association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: The American Thyroid Association Guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid, 2016, 26(1), 1-133.
[http://dx.doi.org/10.1089/thy.2015.0020] [PMID: 26462967]
[4]
Vuong, H.G.; Duong, U.N.; Altibi, A.M.; Ngo, H.T.; Pham, T.Q.; Tran, H.M.; Gandolfi, G.; Hassell, L. A meta-analysis of prognostic roles of molecular markers in papillary thyroid carcinoma. Endocr. Connect., 2017, 6(3), R8-R17.
[http://dx.doi.org/10.1530/EC-17-0010] [PMID: 28219937]
[5]
Brauner, E.; Gunda, V.; Vanden Borre, P.; Zurakowski, D.; Kim, Y.S.; Dennett, K.V.; Amin, S.; Freeman, G.J.; Parangi, S. Combining BRAF inhibitor and anti PD-L1 antibody dramatically improves tumor regression and anti tumor immunity in an immunocompetent murine model of anaplastic thyroid cancer. Oncotarget, 2016, 7(13), 17194-17211.
[http://dx.doi.org/10.18632/oncotarget.7839] [PMID: 26943572]
[6]
Ferrari, S.M.; Fallahi, P.; Galdiero, M.R.; Ruffilli, I.; Elia, G.; Ragusa, F.; Paparo, S.R.; Patrizio, A.; Mazzi, V.; Varricchi, G.; Marone, G.; Antonelli, A. Immune and inflammatory cells in thyroid cancer microenvironment. Int. J. Mol. Sci., 2019, 20(18), 4413.
[http://dx.doi.org/10.3390/ijms20184413] [PMID: 31500315]
[7]
Imam, S.; Dar, P.; Paparodis, R.; Almotah, K.; Al-Khudhair, A.; Hasan, S.A.; Salim, N.; Jaume, J.C. Nature of coexisting thyroid autoimmune disease determines success or failure of tumor immunity in thyroid cancer. J. Immunother. Cancer, 2019, 7(1), 3.
[http://dx.doi.org/10.1186/s40425-018-0483-y] [PMID: 30616690]
[8]
Liyanarachchi, S.; Li, W.; Yan, P.; Bundschuh, R.; Brock, P.; Senter, L.; Ringel, M.D.; de la Chapelle, A.; He, H. Genome-Wide expression screening discloses long noncoding RNAs involved in thyroid carcinogenesis. J. Clin. Endocrinol. Metab., 2016, 101(11), 4005-4013.
[http://dx.doi.org/10.1210/jc.2016-1991] [PMID: 27459529]
[9]
Lei, H.; Gao, Y.; Xu, X. LncRNA TUG1 influences papillary thyroid cancer cell proliferation, migration and EMT formation through targeting miR-145. Acta Biochim. Biophys. Sin. (Shanghai), 2017, 49(7), 588-597.
[http://dx.doi.org/10.1093/abbs/gmx047] [PMID: 28645161]
[10]
Teng, H.; Mao, F.; Liang, J.; Xue, M.; Wei, W.; Li, X.; Zhang, K.; Feng, D.; Liu, B.; Sun, Z. Transcriptomic signature associated with carcinogenesis and aggressiveness of papillary thyroid carcinoma. Theranostics, 2018, 8(16), 4345-4358.
[http://dx.doi.org/10.7150/thno.26862] [PMID: 30214625]
[11]
Jiang, M.C.; Ni, J.J.; Cui, W.Y.; Wang, B.Y.; Zhuo, W. Emerging roles of lncRNA in cancer and therapeutic opportunities. Am. J. Cancer Res., 2019, 9(7), 1354-1366.
[PMID: 31392074]
[12]
Yu, W.D.; Wang, H.; He, Q.F.; Xu, Y.; Wang, X.C. Long noncoding RNAs in cancer-immunity cycle. J. Cell. Physiol., 2018, 233(9), 6518-6523.
[http://dx.doi.org/10.1002/jcp.26568] [PMID: 29574911]
[13]
Huang, Z.; Xiao, C.; Zhang, F.; Zhou, Z.; Yu, L.; Ye, C.; Huang, W.; Li, N. A novel framework to predict breast cancer prognosis using immune-associated LncRNAs. Front. Genet., 2021, 11, 634195.
[http://dx.doi.org/10.3389/fgene.2020.634195] [PMID: 33584821]
[14]
Shen, S.; Chen, X.; Hu, X.; Huo, J.; Luo, L.; Zhou, X. Predicting the immune landscape of invasive breast carcinoma based on the novel signature of immune-related lncRNA. Cancer Med., 2021, 10(18), 6561-6575.
[http://dx.doi.org/10.1002/cam4.4189] [PMID: 34378851]
[15]
Vishnubalaji, R.; Shaath, H.; Elkord, E.; Alajez, N.M. Long non-coding RNA (lncRNA) transcriptional landscape in breast cancer identifies LINC01614 as non-favorable prognostic biomarker regulated by TGFβ and Focal Adhesion Kinase (FAK) signaling. Cell Death Discov., 2019, 5, 109.
[http://dx.doi.org/10.1038/s41420-019-0190-6] [PMID: 31263577]
[16]
Wang, Y.; Song, B.; Zhu, L.; Zhang, X. Long non-coding RNA, LINC01614 as a potential biomarker for prognostic prediction in breast cancer. PeerJ, 2019, 7, e7976.
[http://dx.doi.org/10.7717/peerj.7976] [PMID: 31741788]
[17]
Sun, Y.; Ling, C. Analysis of the long non-coding RNA LINC01614 in non-small cell lung cancer. Medicine (Baltimore), 2019, 98(30), e16437.
[http://dx.doi.org/10.1097/MD.0000000000016437] [PMID: 31348244]
[18]
Yang, H.; Yang, W.; Dai, W.; Ma, Y.; Zhang, G. LINC00667 promotes the proliferation, migration, and pathological angiogenesis in non-small cell lung cancer through stabilizing VEGFA by EIF4A3. Cell Biol. Int., 2020, 44(8), 1671-1680.
[http://dx.doi.org/10.1002/cbin.11361] [PMID: 32281700]
[19]
Zhou, W.; Liu, T.; Saren, G.; Liao, L.; Fang, W.; Zhao, H. Comprehensive analysis of differentially expressed long non-coding RNAs in non-small cell lung cancer. Oncol. Lett., 2019, 18(2), 1145-1156.
[http://dx.doi.org/10.3892/ol.2019.10414] [PMID: 31423174]
[20]
Zhu, M.; Lv, Q.; Huang, H.; Sun, C.; Pang, D.; Wu, J. Identification of a four-long non-coding RNA signature in predicting breast cancer survival. Oncol. Lett., 2020, 19(1), 221-228.
[PMID: 31897133]
[21]
Chen, Y.; Bi, F.; An, Y.; Yang, Q. Identification of pathological grade and prognosis-associated lncRNA for ovarian cancer. J. Cell. Biochem., 2019, 120(9), 14444-14454.
[http://dx.doi.org/10.1002/jcb.28704] [PMID: 31034644]
[22]
Gu, J.; Zhang, X.; Miao, R.; Ma, X.; Xiang, X.; Fu, Y.; Liu, C.; Niu, W.; Qu, K. A three-long non-coding RNA-expression-based risk score system can better predict both overall and recurrence-free survival in patients with small hepatocellular carcinoma. Aging (Albany NY), 2018, 10(7), 1627-1639.
[http://dx.doi.org/10.18632/aging.101497] [PMID: 30018179]
[23]
Zhou, M.; Zhang, Z.; Bao, S.; Hou, P.; Yan, C.; Su, J.; Sun, J. Computational recognition of lncRNA signature of tumor-infiltrating B lymphocytes with potential implications in prognosis and immunotherapy of bladder cancer. Brief. Bioinform., 2021, 22(3), 047.
[http://dx.doi.org/10.1093/bib/bbaa047]
[24]
Nie, Y.; Jiao, Y.; Li, Y.; Li, W. Investigation of the clinical significance and prognostic value of the lncRNA ACVR2B-As1 in liver cancer. BioMed Res. Int., 2019, 2019, 4602371.
[http://dx.doi.org/10.1155/2019/4602371] [PMID: 31886217]
[25]
Li, Q.; Wang, P.; Sun, C.; Wang, C.; Sun, Y. Integrative analysis of methylation and transcriptome identified epigenetically regulated lncRNAs with prognostic relevance for thyroid cancer. Front. Bioeng. Biotechnol., 2020, 7, 439.
[http://dx.doi.org/10.3389/fbioe.2019.00439] [PMID: 31998704]
[26]
Li, X.; Dai, D.; Wang, H.; Wu, B.; Wang, R. Identification of prognostic signatures associated with long-term overall survival of thyroid cancer patients based on a competing endogenous RNA network. Genomics, 2020, 112(2), 1197-1207.
[http://dx.doi.org/10.1016/j.ygeno.2019.07.005] [PMID: 31295545]
[27]
Dong, X.; Jin, C.; Chen, D.; Chen, Y.; Ye, Z.Q.; Zhang, X.; Huang, X.; Zhang, W.; Gu, D.N. Genomic instability-related LncRNA signature predicts the prognosis and highlights LINC01614 is a tumor microenvironment-related oncogenic lncRNA of papillary thyroid carcinoma. Front. Oncol., 2021, 11, 737867.
[http://dx.doi.org/10.3389/fonc.2021.737867] [PMID: 34604079]
[28]
Wang, H.; Wu, J.; Guo, W. SP1-Mediated upregulation of lncRNA LINC01614 functions a ceRNA for miR-383 to facilitate glioma progression through regulation of ADAM12. OncoTargets Ther., 2020, 13, 4305-4318.
[http://dx.doi.org/10.2147/OTT.S242854] [PMID: 32547064]
[29]
Sui, Y.X.; Zhao, D.L.; Yu, Y.; Wang, L.C. The role, function, and mechanism of long intergenic noncoding RNA1184 (linc01184) in colorectal cancer. Dis. Markers, 2021, 2021, 8897906.
[http://dx.doi.org/10.1155/2021/8897906] [PMID: 33564344]
[30]
Wang, W.; Li, J.; Lin, F.; Guo, J.; Zhao, J. Identification of N6-methyladenosine-related lncRNAs for patients with primary glioblastoma. Neurosurg. Rev., 2021, 44(1), 463-470.
[http://dx.doi.org/10.1007/s10143-020-01238-x] [PMID: 31938968]
[31]
Qiu, X.; Tian, Y.; Xu, J.; Jiang, X.; Liu, Z.; Qi, X.; Chang, X.; Zhao, J.; Huang, J. Development and validation of an immune-related long non-coding RNA prognostic model in glioma. J. Cancer, 2021, 12(14), 4264-4276.
[http://dx.doi.org/10.7150/jca.53831] [PMID: 34093827]
[32]
Li, Z.; Lin, W.; Zheng, J.; Hong, W.; Zou, J.; Zhang, T.; Chen, Y.; Lu, H. Identification of immune-related lncRNAs to improve the prognosis prediction for patients with papillary thyroid cancer. Biosci. Rep., 2021, 41(2), BSR20204086.
[http://dx.doi.org/10.1042/BSR20204086] [PMID: 33554245]

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