Diagnosis and Prediction of Endometrial Carcinoma Using Machine Learning and Artificial Neural Networks Based on Public Databases.

Dongli Zhao, Zhe Zhang, Zhonghuang Wang, Zhenglin Du, Meng Wu, Tingting Zhang, Jialu Zhou, Wenming Zhao, Yuanguang Meng
Author Information
  1. Dongli Zhao: Department of Obstetrics & Gynecology, Chinese People's Liberation Army (PLA) Medical School, No. 28, Fuxing Road, Haidian District, Beijing 100853, China.
  2. Zhe Zhang: Department of Obstetrics and Gynecology, Seventh Medical Center of Chinese PLA General Hospital, No. 5, Nanmencang, Dongsishitiao, Dongcheng District, Beijing 100700, China.
  3. Zhonghuang Wang: National Genomics Data Center & CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Building 104, Courtyard 1, Beichen West Road, Chaoyang District, Beijing 100101, China.
  4. Zhenglin Du: National Genomics Data Center & CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Building 104, Courtyard 1, Beichen West Road, Chaoyang District, Beijing 100101, China. ORCID
  5. Meng Wu: Medical College, Graduate School of Nankai University, No. 94, Weijin Road, Nankai District, Tianjin 300110, China.
  6. Tingting Zhang: Department of Obstetrics & Gynecology, Chinese People's Liberation Army (PLA) Medical School, No. 28, Fuxing Road, Haidian District, Beijing 100853, China.
  7. Jialu Zhou: Department of Obstetrics & Gynecology, Chinese People's Liberation Army (PLA) Medical School, No. 28, Fuxing Road, Haidian District, Beijing 100853, China.
  8. Wenming Zhao: National Genomics Data Center & CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Building 104, Courtyard 1, Beichen West Road, Chaoyang District, Beijing 100101, China.
  9. Yuanguang Meng: Department of Obstetrics & Gynecology, Chinese People's Liberation Army (PLA) Medical School, No. 28, Fuxing Road, Haidian District, Beijing 100853, China. ORCID

Abstract

Endometrial carcinoma (EC), a common female reproductive system malignant tumor, affects thousands of people with high morbidity and mortality worldwide. This study was aimed at developing a prediction model for the diagnosis of EC in the general population. First, we obtained datasets GSE63678, GSE106191, and GSE115810 from the Gene Expression Omnibus (GEO) database, dataset GSE17025 from the GEO database, and the RNA sequence of EC from The Cancer Genome Atlas (TCGA) database to constitute the training, test, and validation groups, respectively. Subsequently, the 96 most significantly differentially expressed genes (DEGs) were identified and analyzed for function and pathway enrichment in the training group. Next, we acquired the disease-specific genes by random forest and established an artificial neural network for the diagnosis. Receiver operating characteristic (ROC) curves were utilized to identify the signature across the three groups. Finally, immune infiltration was analyzed to reveal tumor-immune microenvironment (TIME) alterations in EC. The top 96 DEGs (77 down-regulated and 19 up-regulated genes) were primarily enriched in the interleukin-17 signaling pathway, protein digestion and absorption, and transcriptional misregulation in cancer. Subsequently, 14 characterizing genes of EC were identified by random forest. In the training, test, and validation groups, the artificial neural network was constructed with high diagnostic accuracies of 0.882, 0.864, and 0.839, respectively, and areas under the ROC curve (AUCs) of 0.928, 0.921, and 0.782, respectively. Finally, resting and activated mast cells were found to have increased in TIME. We constructed an artificial diagnostic model with excellent reliability for EC and uncovered variations in the immunological ecosystem of EC through integrated bioinformatics approaches, which might be potential diagnostic targets for EC.

Keywords

References

  1. CA Cancer J Clin. 2019 Jul;69(4):258-279 [PMID: 31074865]
  2. Nat Rev Cancer. 2021 May;21(5):298-312 [PMID: 33750922]
  3. Proteomics Clin Appl. 2010 Jan;4(1):17-31 [PMID: 21137014]
  4. Mod Pathol. 2019 Mar;32(3):405-414 [PMID: 30315273]
  5. Comput Struct Biotechnol J. 2021 Sep 04;19:5008-5018 [PMID: 34589181]
  6. J Surg Oncol. 2013 Jun;107(7):746-51 [PMID: 23280473]
  7. Cancer Discov. 2016 Jun;6(6):630-49 [PMID: 27072748]
  8. Transl Cancer Res. 2020 Dec;9(12):7767-7777 [PMID: 35117379]
  9. Oncol Rep. 2012 Apr;27(4):1049-57 [PMID: 22200690]
  10. Eur J Obstet Gynecol Reprod Biol. 2021 Aug;263:100-105 [PMID: 34175583]
  11. Transl Cancer Res. 2020 Dec;9(12):7725-7733 [PMID: 35117375]
  12. N Engl J Med. 2009 Aug 27;361(9):888-98 [PMID: 19710487]
  13. J Obstet Gynaecol Res. 2011 Jun;37(6):483-8 [PMID: 21114579]
  14. Mol Ther Oncolytics. 2021 Jul 10;22:294-306 [PMID: 34553020]
  15. Int J Mol Sci. 2021 Jun 29;22(13): [PMID: 34209703]
  16. Carcinogenesis. 2008 Apr;29(4):880-6 [PMID: 18258601]
  17. Front Genet. 2021 Nov 01;12:763537 [PMID: 34790227]
  18. Clin Proteomics. 2019 Aug 28;16:34 [PMID: 31467500]
  19. Gynecol Oncol. 2013 Feb;128(2):300-8 [PMID: 23200916]
  20. J Reprod Med. 1995 Aug;40(8):553-5 [PMID: 7473450]
  21. Minim Invasive Ther Allied Technol. 2021 Oct;30(5):288-295 [PMID: 34218728]
  22. Asian Pac J Cancer Prev. 2018 Apr 25;19(4):969-975 [PMID: 29693365]
  23. CA Cancer J Clin. 2021 May;71(3):209-249 [PMID: 33538338]
  24. Nucleic Acids Res. 1998 Jun 15;26(12):3059-65 [PMID: 9611255]
  25. Med Image Anal. 2022 May;78:102384 [PMID: 35217454]
  26. Am J Obstet Gynecol. 1988 Mar;158(3 Pt 1):489-92 [PMID: 3348309]
  27. Biomolecules. 2021 Jan 12;11(1): [PMID: 33445802]
  28. Am J Obstet Gynecol. 1986 Nov;155(5):1097-102 [PMID: 3465243]
  29. Thorac Cancer. 2022 Apr;13(7):1027-1039 [PMID: 35178875]
  30. Annu Rev Pathol. 2019 Jan 24;14:339-367 [PMID: 30332563]
  31. Mol Med Rep. 2021 Jan;23(1): [PMID: 33179082]
  32. Cell. 2013 Mar 14;152(6):1237-51 [PMID: 23498934]
  33. Histol Histopathol. 2020 Sep;35(9):997-1005 [PMID: 32378728]
  34. Genes (Basel). 2022 Jan 25;13(2): [PMID: 35205261]
  35. Ultrasound Obstet Gynecol. 2022 Apr 6;: [PMID: 35385178]
  36. Ecancermedicalscience. 2020 May 06;14:1035 [PMID: 32419847]
  37. PLoS One. 2022 Apr 12;17(4):e0266339 [PMID: 35413062]
  38. J Obstet Gynaecol Res. 2021 Aug;47(8):2577-2585 [PMID: 33973305]
  39. Nat Rev Cancer. 2014 May;14(5):329-41 [PMID: 24722429]
  40. Am J Pathol. 2010 Aug;177(2):1031-41 [PMID: 20616342]
  41. FEBS J. 2011 Jan;278(1):16-27 [PMID: 21087457]
  42. J Immunol. 2015 Sep 15;195(6):2591-600 [PMID: 26259585]
  43. Histopathology. 2020 Jan;76(1):11-24 [PMID: 31846522]
  44. Adv Anat Pathol. 2009 Jan;16(1):1-22 [PMID: 19098463]
  45. Prostate. 2009 Jun 15;69(9):976-81 [PMID: 19274666]
  46. Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2640-5 [PMID: 18268320]
  47. Prim Care. 2021 Dec;48(4):555-567 [PMID: 34752269]
  48. Adv Exp Med Biol. 2020;1240:47-58 [PMID: 32060887]
  49. Cell Rep Med. 2021 Jun 15;2(6):100318 [PMID: 34195683]
  50. Biomedicines. 2021 Jun 02;9(6): [PMID: 34199461]
  51. J Clin Pathol. 2017 Nov;70(11):941-946 [PMID: 28389441]
  52. Biomolecules. 2019 Dec 30;10(1): [PMID: 31905969]
  53. Minerva Ginecol. 2014 Jun;66(3):243-9 [PMID: 24971780]
  54. J Exp Clin Cancer Res. 2018 Mar 2;37(1):41 [PMID: 29499765]
  55. J Natl Compr Canc Netw. 2018 Feb;16(2):170-199 [PMID: 29439178]
  56. Nat Rev Cancer. 2016 Jul;16(7):431-46 [PMID: 27282249]

MeSH Term

Ecosystem
Endometrial Neoplasms
Female
Humans
Machine Learning
Neural Networks, Computer
Reproducibility of Results
Tumor Microenvironment

Word Cloud

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