Abstract
The purpose of the study was to explore the application of artificial neural network model in the auxiliary diagnosis of lung cancer and compare the effects of back-propagation (BP) neural network with Fisher discrimination model for lung cancer screening by the combined detections of four biomarkers of p16, RASSF1A and FHIT gene promoter methylation levels and the relative telomere length. Real-time quantitative methylation-specific PCR was used to detect the levels of three-gene promoter methylation, and real-time PCR method was applied to determine the relative telomere length. BP neural network and Fisher discrimination analysis were used to establish the discrimination diagnosis model. The levels of three-gene promoter methylation in patients with lung cancer were significantly higher than those of the normal controls. The values of Z(P) in two groups were 2.641 (0.008), 2.075 (0.038) and 3.044 (0.002), respectively. The relative telomere lengths of patients with lung cancer (0.93 ± 0.32) were significantly lower than those of the normal controls (1.16 ± 0.57), t = 4.072, P < 0.001. The areas under the ROC curve (AUC) and 95 % CI of prediction set from Fisher discrimination analysis and BP neural network were 0.670 (0.569–0.761) and 0.760 (0.664–0.840). The AUC of BP neural network was higher than that of Fisher discrimination analysis, and Z(P) was 0.76. Four biomarkers are associated with lung cancer. BP neural network model for the prediction of lung cancer is better than Fisher discrimination analysis, and it can provide an excellent and intelligent diagnosis tool for lung cancer.
Similar content being viewed by others
References
Aguiar FS, Torres RC, Pinto JV, Kritski AL, Seixas JM, Mello FC (2016) Development of two artificial neural network models to support the diagnosis of pulmonary tuberculosis in hospitalized patients in Rio de Janeiro, Brazil. Med Biol Eng Comput. doi:10.1007/s11517-016-1465-1
Bassi P, Sacco E, De Marco V, Aragona M, Volpe A (2007) Prognostic accuracy of an artificial neural network in patients undergoing radical cystectomy for bladder cancer: a comparison with logistic regression analysis. BJU Int 99:1007–1012. doi:10.1111/j.1464-410X.2007.06755.x
Boukamp P, Popp S, Krunic D (2005) Telomere-dependent chromosomal instability. J Investig Dermatol Symp Proc 10:89–94. doi:10.1111/j.1087-0024.2005.200401.x
Cawthon RM (2009) Telomere length measurement by a novel monochrome multiplex quantitative PCR method. Nucleic Acids Res 37:e21. doi:10.1093/nar/gkn1027
Feng F, Wu Y, Nie G, Ni R (2012) The effect of artificial neural network model combined with six tumor markers in auxiliary diagnosis of lung cancer. J Med Syst 36:2973–2980. doi:10.1007/s10916-011-9775-1
Feng F, Yang Y, Li Z, Song J, Zhu H, Wang L, Zhao Y, Xu D, Wu Y, Wu Y et al (2015) Changes in telomere length and telomerase activity in human bronchial epithelial cells induced by coal tar pitch extract. Toxicol Res 4:1535–1544. doi:10.1039/c5tx00121h
Fukushige S, Horii A (2013) DNA methylation in cancer: a gene silencing mechanism and the clinical potential of its biomarkers. Tohoku J Exp Med 229:173–185
Hanai T, Yatabe Y, Nakayama Y, Takahashi T, Honda H, Mitsudomi T, Kobayashi T (2003) Prognostic models in patients with non-small-cell lung cancer using artificial neural networks in comparison with logistic regression. Cancer Sci 94:473–477
Heaphy CM, Meeker AK (2011) The potential utility of telomere-related markers for cancer diagnosis. J Cell Mol Med 15:1227–1238. doi:10.1111/j.1582-4934.2011.01284.x
Hsu HS, Chen TP, Hung CH, Wen CK, Lin RK, Lee HC, Wang YC (2007) Characterization of a multiple epigenetic marker panel for lung cancer detection and risk assessment in plasma. Cancer 110:2019–2026. doi:10.1002/cncr.23001
Hwang YN, Lee JH, Kim GY, Jiang YY, Kim SM (2015) Classification of focal liver lesions on ultrasound images by extracting hybrid textural features and using an artificial neural network. Bio-Med Mater Eng 26(Suppl 1):S1599–S1611. doi:10.3233/bme-151459
Ingles ED, Deakin JE (2015) Global DNA Methylation patterns on marsupial and devil facial tumour chromosomes. Mol Cytogenet 8:74. doi:10.1186/s13039-015-0176-x
Jang JS, Choi YY, Lee WK, Choi JE, Cha SI, Kim YJ, Kim CH, Kam S, Jung TH, Park JY (2008) Telomere length and the risk of lung cancer. Cancer Sci 99:1385–1389. doi:10.1111/j.1349-7006.2008.00831.x
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69–90. doi:10.3322/caac.20107
Jones PA, Baylin SB (2002) The fundamental role of epigenetic events in cancer. Nat Rev Genet 3:415–428. doi:10.1038/nrg816
Li W, Deng J, Jiang P, Tang J (2010) Association of 5′-CpG island hypermethylation of the FHIT gene with lung cancer in southern-central Chinese population. Cancer Biol Ther 10:997–1000. doi:10.4161/cbt.10.10.13231
Liu Z, Li W, Lei Z, Zhao J, Chen XF, Liu R, Peng X, Wu ZH, Chen J, Liu H et al (2010) CpG island methylator phenotype involving chromosome 3p confers an increased risk of non-small cell lung cancer. J Thorac Oncol 5:790–797
Lu L, Katsaros D, de la Longrais IA, Sochirca O, Yu H (2007) Hypermethylation of let-7a-3 in epithelial ovarian cancer is associated with low insulin-like growth factor-II expression and favorable prognosis. Cancer Res 67:10117–10122. doi:10.1158/0008-5472.can-07-2544
Marchevsky AM, Tsou JA, Laird-Offringa IA (2004) Classification of individual lung cancer cell lines based on DNA methylation markers: use of linear discriminant analysis and artificial neural networks. J Mol Diagn JMD 6:28–36. doi:10.1016/s1525-1578(10)60488-6
Mat-Isa NA, Mashor MY, Othman NH (2008) An automated cervical pre-cancerous diagnostic system. Artif Intell Med 42:1–11. doi:10.1016/j.artmed.2007.09.002
Moore LE, Pfeiffer RM, Poscablo C, Real FX, Kogevinas M, Silverman D, Garcia-Closas R, Chanock S, Tardon A, Serra C et al (2008) Genomic DNA hypomethylation as a biomarker for bladder cancer susceptibility in the Spanish Bladder Cancer Study: a case-control study. Lancet Oncol 9:359–366. doi:10.1016/s1470-2045(08)70038-x
Musa KH, Abdullah A, Al-Haiqi A (2016) Determination of DPPH free radical scavenging activity: application of artificial neural networks. Food Chem 194:705–711. doi:10.1016/j.foodchem.2015.08.038
Nie GJ, Feng FF, Wu YJ, Wu YM (2009) Diagnosis and prediction of lung cancer through different classification techniques with tumor markers. Chin J Ind Hyg Occup Dis (Zhonghua laodong weisheng zhiyebing zazhi) 27:257–261
Rossmann MP, Luo W, Tsaponina O, Chabes A, Stillman B (2011) A common telomeric gene silencing assay is affected by nucleotide metabolism. Mol Cell 42:127–136. doi:10.1016/j.molcel.2011.03.007
Siegel R, Ward E, Brawley O, Jemal A (2011) Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin 61:212–236. doi:10.3322/caac.20121
Song H, Yi J, Zhang Y, Wang R, Chen L (2011) DNA methylation of tumor suppressor genes located on chromosome 3p in non-small cell lung cancer. Chin J Lung Cancer (Zhongguo fei ai za zhi) 14:233–238. doi:10.3779/j.issn.1009-3419.2011.03.09
Suga Y, Miyajima K, Oikawa T, Maeda J, Usuda J, Kajiwara N, Ohira T, Uchida O, Tsuboi M, Hirano T et al (2008) Quantitative p16 and ESR1 methylation in the peripheral blood of patients with non-small cell lung cancer. Oncol Rep 20:1137–1142
Tan S, Sun C, Wei X, Li Y, Wu Y, Yan Z, Feng F, Wang J (2013) Quantitative assessment of lung cancer associated with genes methylation in the peripheral blood. Exp Lung Res 39:182–190. doi:10.3109/01902148.2013.790096
Vizoso M, Puig M, Carmona FJ, Maqueda M, Velasquez A, Gomez A, Labernadie A, Lugo R, Gabasa M, Rigat-Brugarolas LG et al (2015) Aberrant DNA methylation in non-small cell lung cancer-associated fibroblasts. Carcinogenesis. doi:10.1093/carcin/bgv146
Wang L, Aakre JA, Jiang R, Marks RS, Wu Y, Chen J, Thibodeau SN, Pankratz VS, Yang P (2010) Methylation markers for small cell lung cancer in peripheral blood leukocyte DNA. J Thorac Oncol 5:778–785. doi:10.1097/JTO.0b013e3181d6e0b3
Wu Y, Wu Y, Wang J, Yan Z, Qu L, Xiang B, Zhang Y (2011) An optimal tumor marker group-coupled artificial neural network for diagnosis of lung cancer. Expert Syst Appl 38:11329–11334. doi:10.1016/j.eswa.2011.02.183
Yan W, Herman JG, Guo M (2015) Epigenome-based personalized medicine in human cancer. Epigenomics. doi:10.2217/epi.15.84
Zhang H, Zhang S, Zhang Z, Jia H, Gu S, Zhao D (2010) Prognostic value of methylation status of RASSF1A gene as an independent factor of non-small cell lung cancer. Chin J Lung Cancer (Zhongguo fei ai za zhi) 13:311–316. doi:10.3779/j.issn.1009-3419.2010.04.08
Zhang Y, Wang R, Song H, Huang G, Yi J, Zheng Y, Wang J, Chen L (2011) Methylation of multiple genes as a candidate biomarker in non-small cell lung cancer. Cancer Lett 303:21–28. doi:10.1016/j.canlet.2010.12.011
Zochbauer-Muller S, Fong KM, Maitra A, Lam S, Geradts J, Ashfaq R, Virmani AK, Milchgrub S, Gazdar AF, Minna JD (2001) 5′ CpG island methylation of the FHIT gene is correlated with loss of gene expression in lung and breast cancer. Cancer Res 61:3581–3585
Acknowledgments
The work was supported by the National Natural Science Foundation of China (NSFC 81573203, 30972457, 81001239) and the Outstanding Youth Grant of Zhengzhou University (No. 1421329082).
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflict of interest
None.
Additional information
Xiaoran Duan and Yongli Yang have contributed equally to this work.
Rights and permissions
About this article
Cite this article
Duan, X., Yang, Y., Tan, S. et al. Application of artificial neural network model combined with four biomarkers in auxiliary diagnosis of lung cancer. Med Biol Eng Comput 55, 1239–1248 (2017). https://doi.org/10.1007/s11517-016-1585-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11517-016-1585-7