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Combinatorial Chemistry & High Throughput Screening

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

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Research Article

Development and Validation of a Five-immune Gene Pair Signature in Endometrial Carcinoma

Author(s): Nan Li, Kai Yu, Zhong Lin* and Dingyuan Zeng*

Volume 24, Issue 2, 2021

Published on: 29 July, 2020

Page: [233 - 245] Pages: 13

DOI: 10.2174/1386207323999200729113641

Price: $65

Abstract

Background: Endometrial cancer (EC) is a common gynecological malignancy worldwide. Immunity is closely related to the occurrence and prognosis of EC. At the same time, immune-related genes have great potential as prognostic markers in many types of cancer.

Objective: Therefore, we attempt to develop immune-related gene markers to enhance prognosis prediction of EC.

Methods: 542 samples of EC gene expression data and clinical follow-up information were downloaded from The Cancer Genome Atlas (TCGA). The samples were randomly divided into two groups, one group as a training set (N=271), and one set as a validation set. (N=271). In the training set, the gene pairs were established based on the relative expression levels of 271 immune genes, and the prognosis-related gene pairs were screened. The lasso was used to select the features, and finally, the robust biomarkers were screened. Finally, the prognostic model of the immune gene pair was established and verified by the validation data set.

Results: 10030 immune gene pair (IRGPs) were obtained, and univariate survival analysis was used to identify 1809 prognostic-related IRGPs (p<0.05). 5-IRGPs were obtained by lasso regression feature selection, and multivariate regression was used to establish 5-IRGPs signature, 5-IRGPs signature is an independent prognostic factor for EC patients, and could be risk stratified in patients with TCGA datasets, age, ethnicity, stage, and histological classification (p<0.05). The mean AUC of survival in both the training set and the validation set was greater than 0.7, indicating that 5-IRGPs signature has superior classification performance in patients with EC. In addition, 5-IRGPs have the highest average C index (0.795) compared to the prognostic characteristics of the three endometrial cancers reported in the past and Stage and Age.

Conclusion: This study constructed a 5-IRGPs signature as a novel prognostic marker for predicting survival in patients with EC.

Keywords: Bioinformatics, immune-related gene pairs, prognostic markers, TCGA, endometrial cancer, malignancy.

« Previous Next »
[1]
Kwasniewski, W.; Gozdzicka-Jozefiak, A.; Wolun-Cholewa, M.; Polak, G.; Sierocinska-Sawa, J.; Kwasniewska, A.; Kotarski, J. Microsatellite polymorphism in the P1 promoter region of the IGF 1 gene is associated with endometrial cancer. Mol. Med. Rep., 2016, 13(6), 4950-4958.
[http://dx.doi.org/10.3892/mmr.2016.5181] [PMID: 27121258]
[2]
Ferlay, J.; Soerjomataram, I.; Dikshit, R.; Eser, S.; Mathers, C.; Rebelo, M.; Parkin, D.M.; Forman, D.; Bray, F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer, 2015, 136(5)E359-E386.
[http://dx.doi.org/10.1002/ijc.29210] [PMID: 25220842]
[3]
Screening, P.D.Q. Endometrial Cancer Prevention (PDQ®): Health Professional VersionPDQ Cancer Information Summaries, National Cancer Institute (US): Bethesda (MD);
[4]
Shi, C.; Zhang, Z. Screening of potentially crucial genes and regulatory factors involved in epithelial ovarian cancer using microarray analysis. Oncol. Lett., 2017, 14(1), 725-732.
[http://dx.doi.org/10.3892/ol.2017.6183] [PMID: 28693226]
[5]
Peng, C.; Yang, Q.; Wei, B.; Yuan, B.; Liu, Y.; Li, Y.; Gu, D.; Yin, G.; Wang, B.; Xu, D.; Zhang, X.; Kong, D. Investigation of crucial genes and microRNAs in conventional osteosarcoma using gene expression profiling analysis. Mol. Med. Rep., 2017, 16(5), 7617-7624.
[http://dx.doi.org/10.3892/mmr.2017.7506] [PMID: 28944822]
[6]
Xu, Z.; Zhou, Y.; Shi, F.; Cao, Y.; Dinh, T.L.A.; Wan, J.; Zhao, M. Investigation of differentially-expressed microRNAs and genes in cervical cancer using an integrated bioinformatics analysis. Oncol. Lett., 2017, 13(4), 2784-2790.
[http://dx.doi.org/10.3892/ol.2017.5766] [PMID: 28454467]
[7]
Liu, J.; Feng, M.; Li, S.; Nie, S.; Wang, H.; Wu, S.; Qiu, J.; Zhang, J.; Cheng, W. Identification of molecular markers associated with the progression and prognosis of endometrial cancer: a bioinformatic study. Cancer Cell Int., 2020, 20, 59.
[http://dx.doi.org/10.1186/s12935-020-1140-3] [PMID: 32099532]
[8]
Church, D.N.; Briggs, S.E.; Palles, C.; Domingo, E.; Kearsey, S.J.; Grimes, J.M.; Gorman, M.; Martin, L.; Howarth, K.M.; Hodgson, S.V.; Kaur, K.; Taylor, J.; Tomlinson, I.P. NSECG Collaborators. DNA polymerase ε and δ exonuclease domain mutations in endometrial cancer. Hum. Mol. Genet., 2013, 22(14), 2820-2828.
[http://dx.doi.org/10.1093/hmg/ddt131] [PMID: 23528559]
[9]
O’Mara, T.A.; Zhao, M.; Spurdle, A.B. Meta-analysis of gene expression studies in endometrial cancer identifies gene expression profiles associated with aggressive disease and patient outcome. Sci. Rep., 2016, 6, 36677.
[http://dx.doi.org/10.1038/srep36677] [PMID: 27830726]
[10]
Corrado, G.; Laquintana, V.; Loria, R.; Carosi, M.; de Salvo, L.; Sperduti, I.; Zampa, A.; Cicchillitti, L.; Piaggio, G.; Cutillo, G.; Falcioni, R.; Vizza, E. Endometrial cancer prognosis correlates with the expression of L1CAM and miR34a biomarkers. Journal of experimental & clinical cancer research. CR (East Lansing Mich.), 2018, 37(1), 139.
[11]
Liu, J.; Wan, Y.; Li, S.; Qiu, H.; Jiang, Y.; Ma, X.; Zhou, S.; Cheng, W. Identification of aberrantly methylated differentially expressed genes and associated pathways in endometrial cancer using integrated bioinformatic analysis. Cancer Med., 2020, 9(10), 3522-3536.
[http://dx.doi.org/10.1002/cam4.2956] [PMID: 32170852]
[12]
Liu, L.; Lin, J.; He, H. Identification of potential crucial genes associated with the pathogenesis and prognosis of endometrial cancer. Front. Genet., 2019, 10, 373.
[http://dx.doi.org/10.3389/fgene.2019.00373] [PMID: 31105744]
[13]
Wang, Y.; Ren, F.; Chen, P.; Liu, S.; Song, Z.; Ma, X. Identification of a six-gene signature with prognostic value for patients with endometrial carcinoma. Cancer Med., 2018, 7(11), 5632-5642.
[http://dx.doi.org/10.1002/cam4.1806] [PMID: 30306731]
[14]
Kostareli, E.; Hielscher, T.; Zucknick, M.; Baboci, L.; Wichmann, G.; Holzinger, D.; Mücke, O.; Pawlita, M.; Del Mistro, A.; Boscolo-Rizzo, P.; Da Mosto, M.C.; Tirelli, G.; Plinkert, P.; Dietz, A.; Plass, C.; Weichenhan, D.; Hess, J. Gene promoter methylation signature predicts survival of head and neck squamous cell carcinoma patients. Epigenetics, 2016, 11(1), 61-73.
[http://dx.doi.org/10.1080/15592294.2015.1137414] [PMID: 26786582]
[15]
Zhang, J.X.; Song, W.; Chen, Z.H.; Wei, J.H.; Liao, Y.J.; Lei, J.; Hu, M.; Chen, G.Z.; Liao, B.; Lu, J.; Zhao, H.W.; Chen, W.; He, Y.L.; Wang, H.Y.; Xie, D.; Luo, J.H. Prognostic and predictive value of a microRNA signature in stage II colon cancer: a microRNA expression analysis. Lancet Oncol., 2013, 14(13), 1295-1306.
[http://dx.doi.org/10.1016/S1470-2045(13)70491-1] [PMID: 24239208]
[16]
Papaemmanuil, E.; Gerstung, M.; Malcovati, L.; Tauro, S.; Gundem, G.; Van Loo, P.; Yoon, C.J.; Ellis, P.; Wedge, D.C.; Pellagatti, A.; Shlien, A.; Groves, M.J.; Forbes, S.A.; Raine, K.; Hinton, J.; Mudie, L.J.; McLaren, S.; Hardy, C.; Latimer, C.; Della Porta, M.G.; O’Meara, S.; Ambaglio, I.; Galli, A.; Butler, A.P.; Walldin, G.; Teague, J.W.; Quek, L.; Sternberg, A.; Gambacorti-Passerini, C.; Cross, N.C.; Green, A.R.; Boultwood, J.; Vyas, P.; Hellstrom-Lindberg, E.; Bowen, D.; Cazzola, M.; Stratton, M.R.; Campbell, P.J. Chronic myeloid disorders working group of the international cancer genome consortium. Clinical and biological implications of driver mutations in myelodysplastic syndromes. Blood, 2013, 122(22), 3616-3627.
[http://dx.doi.org/10.1182/blood-2013-08-518886] [PMID: 24030381]
[17]
Yuan, Y.; Van Allen, E.M.; Omberg, L.; Wagle, N.; Amin-Mansour, A.; Sokolov, A.; Byers, L.A.; Xu, Y.; Hess, K.R.; Diao, L.; Han, L.; Huang, X.; Lawrence, M.S.; Weinstein, J.N.; Stuart, J.M.; Mills, G.B.; Garraway, L.A.; Margolin, A.A.; Getz, G.; Liang, H. Assessing the clinical utility of cancer genomic and proteomic data across tumor types. Nat. Biotechnol., 2014, 32(7), 644-652.
[http://dx.doi.org/10.1038/nbt.2940] [PMID: 24952901]
[18]
Friedman, J.; Hastie, T.; Tibshirani, R. Regularization paths for generalized linear models via coordinate descent. J. Stat. Softw., 2010, 33(1), 1-22.
[http://dx.doi.org/10.18637/jss.v033.i01] [PMID: 20808728]
[19]
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.
[http://dx.doi.org/10.1089/omi.2011.0118] [PMID: 22455463]
[20]
Hänzelmann, S.; Castelo, R.; Guinney, J. GSVA: gene set variation analysis for microarray and RNA-seq data. BMC Bioinformatics, 2013, 14, 7.
[http://dx.doi.org/10.1186/1471-2105-14-7] [PMID: 23323831]
[21]
Liberzon, A.; Subramanian, A.; Pinchback, R.; Thorvaldsdóttir, H.; Tamayo, P.; Mesirov, J.P. Molecular signatures database (MSigDB) 3.0. Bioinformatics, 2011, 27(12), 1739-1740.
[http://dx.doi.org/10.1093/bioinformatics/btr260] [PMID: 21546393]
[22]
Ying, J.; Wang, Q.; Xu, T.; Lyu, J. Establishment of a nine-gene prognostic model for predicting overall survival of patients with endometrial carcinoma. Cancer Med., 2018, 7(6), 2601-2611.
[http://dx.doi.org/10.1002/cam4.1498] [PMID: 29665298]
[23]
Wu, Y.S.; Lin, H.; Chen, D.; Yi, Z.; Zeng, B.; Jiang, Y.; Ren, G. A four-miRNA signature as a novel biomarker for predicting survival in endometrial cancer. Gene, 2019, 697, 86-93.
[http://dx.doi.org/10.1016/j.gene.2019.01.046] [PMID: 30779946]
[24]
Xu, Q.; Yang, Q.; Zhou, Y.; Yang, B.; Jiang, R.; Ai, Z.; Teng, Y. A long noncoding RNAs signature to improve survival prediction in endometrioid endometrial cancer. J. Cell. Biochem., 2018..
[PMID: 30548294]
[25]
Perales, G.; Burguete-Garcia, A.I.; Dimas, J.; Bahena-Roman, M.; Bermudez-Morales, V.H.; Moreno, J.; Madrid-Marina, V. A polymorphism in the AT-hook motif of the transcriptional regulator AKNA is a risk factor for cervical cancer. Biomarkers, 2010, 15(5), 470-474.
[26]
Gao, X.; Wu, Y.; Qiao, L.; Feng, X. SENP2 suppresses NF-κB activation and sensitizes breast cancer cells to doxorubicin. Eur. J. Pharmacol., 2019, 854, 179-186.
[http://dx.doi.org/10.1016/j.ejphar.2019.03.051] [PMID: 30940449]
[27]
Watanabe, M.; Kanao, K.; Suzuki, S.; Muramatsu, H.; Morinaga, S.; Kajikawa, K.; Kobayashi, I.; Nishikawa, G.; Kato, Y.; Zennami, K.; Nakamura, K.; Tsuzuki, T.; Yoshikawa, K.; Ueda, R.; Sumitomo, M. Increased infiltration of CCR4-positive regulatory T cells in prostate cancer tissue is associated with a poor prognosis. Prostate, 2019, 79(14), 1658-1665.
[http://dx.doi.org/10.1002/pros.23890] [PMID: 31390096]
[28]
Kar, R.; Singha, P.K.; Venkatachalam, M.A.; Saikumar, P. A novel role for MAP1 LC3 in nonautophagic cytoplasmic vacuolation death of cancer cells. Oncogene, 2009, 28(28), 2556-2568.
[http://dx.doi.org/10.1038/onc.2009.118] [PMID: 19448671]
[29]
Tang, W.; Zhou, W.; Xiang, L.; Wu, X.; Zhang, P.; Wang, J.; Liu, G.; Zhang, W.; Peng, Y.; Huang, X.; Cai, J.; Bai, Y.; Bai, L.; Zhu, W.; Gu, H.; Xiong, J.; Ye, C.; Li, A.; Liu, S.; Wang, J. The p300/YY1/miR-500a-5p/HDAC2 signalling axis regulates cell proliferation in human colorectal cancer. Nat. Commun., 2019, 10(1), 663.
[http://dx.doi.org/10.1038/s41467-018-08225-3] [PMID: 30737378]
[30]
Fan, H.; Zhang, Y.S. miR-490-3p modulates the progression of prostate cancer through regulating histone deacetylase 2. Eur. Rev. Med. Pharmacol. Sci., 2019, 23(2), 539-546.
[PMID: 30720161]
[31]
Wang, Z.; Kang, W.; You, Y.; Pang, J.; Ren, H.; Suo, Z.; Liu, H.; Zheng, Y. USP7: Novel drug target in cancer therapy. Front. Pharmacol., 2019, 10, 427.
[http://dx.doi.org/10.3389/fphar.2019.00427] [PMID: 31114498]
[32]
Cotte, A.K.; Aires, V.; Fredon, M.; Limagne, E.; Derangère, V.; Thibaudin, M.; Humblin, E.; Scagliarini, A.; de Barros, J.P.; Hillon, P.; Ghiringhelli, F.; Delmas, D. Lysophosphatidylcholine acyltransferase 2-mediated lipid droplet production supports colorectal cancer chemoresistance. Nat. Commun., 2018, 9(1), 322.
[http://dx.doi.org/10.1038/s41467-017-02732-5] [PMID: 29358673]
[33]
Zheng, F.; Wang, M.; Li, Y.; Huang, C.; Tao, D.; Xie, F.; Zhang, H.; Sun, J.; Zhang, C.; Gu, C.; Wang, Z.; Jiang, G. CircNR3C1 inhibits proliferation of bladder cancer cells by sponging miR-27a-3p and downregulating cyclin D1 expression. Cancer Lett., 2019, 460, 139-151.
[http://dx.doi.org/10.1016/j.canlet.2019.06.018] [PMID: 31255724]
[34]
Rangel, R.; Guzman-Rojas, L.; Kodama, T.; Kodama, M.; Newberg, J.Y.; Copeland, N.G.; Jenkins, N.A. Identification of new tumor suppressor genes in triple-negative breast cancer.Cancer Res., 2017.canres.0785.2017,
[http://dx.doi.org/10.1158/0008-5472.CAN-17-0785] [PMID: 28724549]

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