Identification of Crosstalk Genes between Lung Adenocarcinoma and Periodontitis


Cite item

Full Text

Abstract

Background:Lung adenocarcinoma (LUAD) represents a significant global health issue. Smoking contributes to the development of periodontitis and LUAD. The connections between the two are still ambiguous.

Methods:Based on RNA expression data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, differentially expressed genes (DEGs) in Periodontitis and LUAD were collected. Protein-protein interaction (PPI) networks were produced by mining genes intersecting with crossover DEGs. Genes in the subnetwork and the top 15 genes of the topology score were defined as the crosstalk gene. Feature selection and diagnostic model construction were conducted based on Recursive Feature Elimination (RFE) and support vector machines (SVM). additionally, we analyzed the immune cells and signaling pathways influenced by the crosstalk gene.

Results:A total of 29 crossover DEGs between Periodontitis and LUAD were filtered, with 20 genes interacting with them in the PPI network. Five subnetworks with similar interaction patterns in the PPI network were detected. Based on the network topology analysis, genes ranking in the top 15 were used to take the intersection with those genes in the 5 subnetworks. Twelve intersecting genes were identified. Based on RFE and SVM algorithms, FKBP11 and MMP13 were considered as the Crosstalk genes for both Periodontitis and LUAD. The diagnostic model composed of FKBP11 and MMP13 showed excellent diagnostic potential. In addition, we found that FKBP11 and MMP13 influenced Macrophages, M1, T cells, CD8 activity, immune-related pathways, and cell cycle pathways.

Conclusion:We identified the crosstalk genes (FKBP11 and MMP13) between periodontitis and LUAD. The two genes affected the comorbidity status between the two diseases through immune cell activity.

About the authors

Pengcheng Wang

Department of Stomatology,, Beijing Chaoyang Hospital, Capital Medical University,

Email: info@benthamscience.net

Hui Yu

Department of Stomatology, Affiliated Zhongshan Hospital of Dalian University

Email: info@benthamscience.net

Xiaoli Gao

Department of Stomatology, Beijing Chaoyang Hospital, Capital Medical University

Email: info@benthamscience.net

Ziyi Guo

Department of Stomatology, Beijing Chaoyang Hospital, Capital Medical University

Email: info@benthamscience.net

Zheng Zhang

Department of Periodontology, Tianjin Stomatological Hospital, Nankai University

Author for correspondence.
Email: info@benthamscience.net

Zuomin Wang

Department of Stomatology, Beijing Chaoyang Hospital, Capital Medical University

Author for correspondence.
Email: info@benthamscience.net

References

  1. Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2021, 71(3), 209-249. doi: 10.3322/caac.21660 PMID: 33538338
  2. Chen, Y.; Wu, H.; Jiao, A.; Tong, J.; Zhu, J.; Zhang, M.; Li, Z.; Li, P. Chinese herbal prescription QYSL prevents progression of lung cancer by targeting tumor microenvironment. Oncologie, 2022, 24(2), 295-307. doi: 10.32604/oncologie.2022.022116
  3. Wang, H.; Fang, J.; Wang, Y.; Li, S.; Wang, Z.; He, W.; Wang, N.; Luo, S.; Zou, H.; Zhang, F. Gene editing in non-small cell lung cancer: Current application and future perspective. Oncologie, 2022, 24(1), 65-83. doi: 10.32604/oncologie.2022.021863
  4. Liu, J.; Gu, M.; Xue, Y.; Wang, Q.; Ren, Y.; Huang, W. Clinical significance of PD-L1 expression and CD8-positive tumor-infiltrating lymphocytes in patients with cavitary lung adenocarcinoma. Oncologie, 2021, 23(3), 439-452. doi: 10.32604/oncologie.2021.017220
  5. Hirsch, F.R.; Scagliotti, G.V.; Mulshine, J.L.; Kwon, R.; Curran, W.J., Jr; Wu, Y.L.; Paz-Ares, L. Lung cancer: Current therapies and new targeted treatments. Lancet, 2017, 389(10066), 299-311. doi: 10.1016/S0140-6736(16)30958-8 PMID: 27574741
  6. Kwon, T.; Lamster, I.B.; Levin, L. Current concepts in the management of periodontitis. Int. Dent. J., 2021, 71(6), 462-476. doi: 10.1111/idj.12630 PMID: 34839889
  7. Ray, R.R. Periodontitis: An oral disease with severe consequences. Appl. Biochem. Biotechnol., 2023, 195(1), 17-32. doi: 10.1007/s12010-022-04127-9 PMID: 36098930
  8. Pai, S.I.; Matheus, H.R.; Guastaldi, F.P.S. Effects of periodontitis on cancer outcomes in the era of immunotherapy. Lancet Healthy Longev., 2023, 4(4), e166-e175. doi: 10.1016/S2666-7568(23)00021-1 PMID: 37003275
  9. Figueira, E.A.; de Rezende, M.L.R.; Torres, S.A.; Garlet, G.P.; Lara, V.S.; Santos, C.F.; Avila-Campos, M.J.; da Silva, J.S.; Campanelli, A.P. Inhibitory signals mediated by programmed death-1 are involved with T-cell function in chronic periodontitis. J. Periodontol., 2009, 80(11), 1833-1844. doi: 10.1902/jop.2009.090057 PMID: 19905953
  10. Dai, Z.; Zhang, J.; Wu, Q.; Fang, H.; Shi, C.; Li, Z.; Lin, C.; Tang, D.; Wang, D. Intestinal microbiota: A new force in cancer immunotherapy. Cell Commun. Signal., 2020, 18(1), 90. doi: 10.1186/s12964-020-00599-6 PMID: 32522267
  11. Schuller, H.M. The impact of smoking and the influence of other factors on lung cancer. Expert Rev. Respir. Med., 2019, 13(8), 761-769. doi: 10.1080/17476348.2019.1645010 PMID: 31311354
  12. Siasos, G.; Tsigkou, V.; Kokkou, E.; Oikonomou, E.; Vavuranakis, M.; Vlachopoulos, C.; Verveniotis, A.; Limperi, M.; Genimata, V.; Papavassiliou, A.; Stefanadis, C.; Tousoulis, D. Smoking and atherosclerosis: Mechanisms of disease and new therapeutic approaches. Curr. Med. Chem., 2014, 21(34), 3936-3948. doi: 10.2174/092986732134141015161539 PMID: 25174928
  13. Shen, W.; Song, Z.; Zhong, X.; Huang, M.; Shen, D.; Gao, P.; Qian, X.; Wang, M.; He, X.; Wang, T.; Li, S.; Song, X. Sangerbox: A comprehensive, interaction-friendly clinical bioinformatics analysis platform. iMeta, 2022, 1(3), e36. doi: 10.1002/imt2.36
  14. 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
  15. 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
  16. Yu, G.; Wang, L.G.; Yan, G.R.; He, Q.Y. DOSE: An R/Bioconductor package for disease ontology semantic and enrichment analysis. Bioinformatics, 2015, 31(4), 608-609. doi: 10.1093/bioinformatics/btu684 PMID: 25677125
  17. Franz, M.; Rodriguez, H.; Lopes, C.; Zuberi, K.; Montojo, J.; Bader, G.D.; Morris, Q. GeneMANIA update 2018. Nucleic Acids Res., 2018, 46(W1), W60-W64. doi: 10.1093/nar/gky311 PMID: 29912392
  18. 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
  19. Kuhn, M. The caret package; R Foundation for Statistical Computing: Vienna, Austria, 2012.
  20. Chen, B.; Khodadoust, M.S.; Liu, C.L.; Newman, A.M.; Alizadeh, A.A. Profiling tumor infiltrating immune cells with CIBERSORT. Methods Mol. Biol., 2018, 1711, 243-259. doi: 10.1007/978-1-4939-7493-1_12 PMID: 29344893
  21. Barbie, D.A.; Tamayo, P.; Boehm, J.S.; Kim, S.Y.; Moody, S.E.; Dunn, I.F.; Schinzel, A.C.; Sandy, P.; Meylan, E.; Scholl, C.; Fröhling, S.; Chan, E.M.; Sos, M.L.; Michel, K.; Mermel, C.; Silver, S.J.; Weir, B.A.; Reiling, J.H.; Sheng, Q.; Gupta, P.B.; Wadlow, R.C.; Le, H.; Hoersch, S.; Wittner, B.S.; Ramaswamy, S.; Livingston, D.M.; Sabatini, D.M.; Meyerson, M.; Thomas, R.K.; Lander, E.S.; Mesirov, J.P.; Root, D.E.; Gilliland, D.G.; Jacks, T.; Hahn, W.C. Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1. Nature, 2009, 462(7269), 108-112. doi: 10.1038/nature08460 PMID: 19847166
  22. Charoentong, P.; Finotello, F.; Angelova, M.; Mayer, C.; Efremova, M.; Rieder, D.; Hackl, H.; Trajanoski, Z. Pan-cancer immunogenomic analyses reveal genotype-immunophenotype relationships and predictors of response to checkpoint blockade. Cell Rep., 2017, 18(1), 248-262. doi: 10.1016/j.celrep.2016.12.019 PMID: 28052254
  23. Hänzelmann, S.; Castelo, R.; Guinney, J. GSVA: Gene set variation analysis for microarray and RNA-Seq data. BMC Bioinformatics, 2013, 14(1), 7. doi: 10.1186/1471-2105-14-7 PMID: 23323831
  24. Wang, X.; Jia, Y.; Wen, L.; Mu, W.; Wu, X.; Liu, T.; Liu, X.; Fang, J.; Luan, Y.; Chen, P.; Gao, J.; Nguyen, K.A.; Cui, J.; Zeng, G.; Lan, P.; Chen, Q.; Cheng, B.; Wang, Z. Porphyromonas gingivalis promotes colorectal carcinoma by activating the hematopoietic NLRP3 inflammasome. Cancer Res., 2021, 81(10), 2745-2759. doi: 10.1158/0008-5472.CAN-20-3827 PMID: 34003774
  25. Sung, C.E.; Lin, F.G.; Huang, R.Y.; Fang, W.H.; Cheng, W.C.; Tsai, Y.W.C.; Chen, W.L. Periodontitis, Helicobacter pylori infection, and gastrointestinal tract cancer mortality. J. Clin. Periodontol., 2022, 49(3), 210-220. doi: 10.1111/jcpe.13590 PMID: 34961943
  26. Kavarthapu, A.; Gurumoorthy, K. Linking chronic periodontitis and oral cancer: A review. Oral Oncol., 2021, 121, 105375. doi: 10.1016/j.oraloncology.2021.105375 PMID: 34140233
  27. Gao, X.; Jiang, C.; Yao, S.; Ma, L.; Wang, X.; Cao, Z. Identification of hub genes related to immune cell infiltration in periodontitis using integrated bioinformatic analysis. J. Periodontal Res., 2022, 57(2), 392-401. doi: 10.1111/jre.12970 PMID: 34993975
  28. Wang, C.C.; Shen, W.J.; Anuraga, G.; Hsieh, Y.H.; Khoa Ta, H.; Xuan, D.; Shen, C.F.; Wang, C.Y.; Wang, W.J. Penetrating exploration of prognostic correlations of the FKBP gene family with lung adenocarcinoma. J. Pers. Med., 2022, 13(1), 49. doi: 10.3390/jpm13010049 PMID: 36675710
  29. Zhang, X.; Deng, Q.; Wan, X.; Zhao, J.; Zheng, X.; Wang, H.; Wang, H.Q.; Yang, W. Pan-cancer analysis reveals the associations between MMP13 high expression and carcinogenesis and its value as a serum diagnostic marker. Aging, 2023, 15(6), 2115-2135. doi: 10.18632/aging.204599 PMID: 37000142
  30. Shih, D.J.H.; Nayyar, N.; Bihun, I.; Dagogo-Jack, I.; Gill, C.M.; Aquilanti, E.; Bertalan, M.; Kaplan, A.; D’Andrea, M.R.; Chukwueke, U.; Ippen, F.M.; Alvarez-Breckenridge, C.; Camarda, N.D.; Lastrapes, M.; McCabe, D.; Kuter, B.; Kaufman, B.; Strickland, M.R.; Martinez-Gutierrez, J.C.; Nagabhushan, D.; De Sauvage, M.; White, M.D.; Castro, B.A.; Hoang, K.; Kaneb, A.; Batchelor, E.D.; Paek, S.H.; Park, S.H.; Martinez-Lage, M.; Berghoff, A.S.; Merrill, P.; Gerstner, E.R.; Batchelor, T.T.; Frosch, M.P.; Frazier, R.P.; Borger, D.R.; Iafrate, A.J.; Johnson, B.E.; Santagata, S.; Preusser, M.; Cahill, D.P.; Carter, S.L.; Brastianos, P.K. Genomic characterization of human brain metastases identifies drivers of metastatic lung adenocarcinoma. Nat. Genet., 2020, 52(4), 371-377. doi: 10.1038/s41588-020-0592-7 PMID: 32203465
  31. Chen, X.; Lei, H.; Cheng, Y.; Fang, S.; Sun, W.; Zhang, X.; Jin, Z. CXCL8, MMP12, and MMP13 are common biomarkers of periodontitis and oral squamous cell carcinoma. Oral Dis., 2022, odi.14419. doi: 10.1111/odi.14419 PMID: 36321868
  32. Lam, R.S.; O’Brien-Simpson, N.M.; Lenzo, J.C.; Holden, J.A.; Brammar, G.C.; Walsh, K.A.; McNaughtan, J.E.; Rowler, D.K.; Van Rooijen, N.; Reynolds, E.C. Macrophage depletion abates Porphyromonas gingivalis-induced alveolar bone resorption in mice. J. Immunol., 2014, 193(5), 2349-2362. doi: 10.4049/jimmunol.1400853 PMID: 25070844
  33. Wang, T.; He, X.; Liu, X.; Liu, Y.; Zhang, W.; Huang, Q.; Liu, W.; Xiong, L.; Tan, R.; Wang, H.; Zeng, H. Weighted gene co-expression network analysis identifies FKBP11 as a key regulator in acute aortic dissection through a NF-kb dependent pathway. Front. Physiol., 2017, 8, 1010. doi: 10.3389/fphys.2017.01010 PMID: 29255427

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2024 Bentham Science Publishers