期刊文献+

利用蛋白质组学与人工神经网络构建大肠癌肝转移诊断模型 被引量:1

A Diagnostic Model for Colorectal Cancer Liver Metastasis by Proteomics and Artificial Neural Network
下载PDF
导出
摘要 目的应用双向电泳联合质谱技术筛选大肠癌肝转移血清特异性标志物,并利用这些标志物以数据挖掘技术构建人工神经网络大肠癌肝转移诊断模型。方法收集大肠癌无肝转移、伴肝转移患者各12例血清样本,同组血清等量混合进行双向电泳,用ImageMaster V5.0软件分析两组蛋白质的差异,差异蛋白质进行MALDI-TOF-MS鉴定。ELISA法测定差异蛋白及CEA含量。用受试者工作曲线评价其对大肠癌肝转移的诊断价值,以人工神经网络方法,筛选出准确度最高者作为大肠癌肝转移诊断模型。结果双向电泳显示,大肠癌伴肝转移组与无肝转移组相比较有4个蛋白有统计学意义,其中2个上调的蛋白质分别是Transferrin和Complement component C9;2个下调的蛋白质分别是Haptoglobin和Isoform 1 of Serum albumin。受试者工作曲线分析与大肠癌肝转移相关性依次为Transferrin>Haptoglobin>CEA。人工神经网络的诊断方法以Transferrin和Haptoglobin这两个蛋白联合建立的模型预测准确度最高,为88.57%,其敏感度为63.64%,特异度为100%。结论利用蛋白质组学与人工神经网络构建了Transferrin与Haptoglobin联合的大肠癌肝转移诊断模型,横断面验证有较高的准确度,开辟了诊断大肠癌肝转移的新方法。 Objective To screen the specific proteins in serum between colorectal cancer pa- tients with liver metastases and without liver metastases by using two dimension electrophore- sis combined with the technology of mass spectrometry, and set up a diagnostic model for colorectal cancer liver metastases through the artificial neural network (ANN) method.Methods The serum was sampled from 12 colorectal cancer patients with liver metastases (CRCLM) and 12 colorectal cancer patients without liver metastases (CRC). The concentrated and desal- ted samples were separated with two dimensional gel electrophoresis (2-DE) in triplicate ex- periments. The gels were scanned by Image Scanner after stained with Coomassie brilliant blue G-250. The biological variations of the protein expression level were analyzed with ImageMaster VS.0 software. The differentially expressed protein spots were identified by matrix- assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS). Transferrin and Haptoglobin were detected by ELISA and CEA was measured by automatic bio- chemistry analyzer in serum between the two group of patients. Receiver operating characteris- tic curve (ROC) was applied to evaluate these three proteins in classifying the two group of patients. The protein was gradually added to set up an ANN model to diagnose CRCLM based on the area under the curve(AUC).The one with the most accuracy was selected as the diag- nostic model for colorectal cancer liver metastases. Results A total of 2 proteins identified as Transferrin and Complement component C9 were found to be significantly increased, and 2 i- dentified to be Haptoglobin and Isoform 1 of Serum albumin significantly decreased in the ser- um samples of colorectal cancer patients with liver metastases.The identified proteins included Haptoglobin, Complement component C9, Isoform 1 of Serum albumin and Transferrin. The or- der was Transferrin, Haptoglobin,CEA by ROC analysis. The ANN model consists of Transferrin and Haptoglobin kept the supreme accuracy to diagnose colorectal cancer liver metastases with 88.57% accuracy, 63.64% sensitivity and 100% specificity, and was selected to be the diagnosis model. Conclusion We can set up an artificial neural network model combining Transferrin and Haptoglobin with higher accuracy to diagnose colorectal cancer liver metastases.
出处 《湖北民族学院学报(医学版)》 2013年第1期5-10,共6页 Journal of Hubei Minzu University(Medical Edition)
基金 广东省高等学校高层次人才项目(粤教师函[2010]79号) 广东省医学科研基金项目(A2011315) 国家自然科学基金(61201437)
关键词 大肠癌 肝转移 双向电泳 人工神经网络 colorectal cancer liver metastases two dimensional gel electrophoresis artificialneural network
  • 相关文献

参考文献20

  • 1Rozen P. Report of the World Organization for Digestive Endoscopy Colorectal Cancer Screening Committee meet- ing, Chicago, 2005 [ J]. Eur J Cancer Prey, 2006, 15 (2) :95-102.
  • 2Hasegawa S, Matsumoto S, Kawashima K, et al. Combined chemotherapy with oral leucovorin (LV) + tegafur/uracil (UFT) and hepatic arterial infusion (HAI) therapy for liver metastasis of colorectal cancer [ J ]. Gan To Kagaku Ryoho, 2005,32 ( 7 ) : 1 045-1 049.
  • 3Petricoin EE, Paweletz CP, Liotta LA. Clinical applications of proteomics : proteomic pattern diagnostics [ J ]. J Mam- mary Gland Biol Neoplasia,2002,7(4) :433-440.
  • 4Petricoin E, Liotta LA. Counterpoint:The vision for a new diagnostic paradigm [ J ]. Clin Chem, 2003,49 ( 8 ) : 1 276- 1 278.
  • 5Kennedy S.Proteomie profiling from human samples: the body fluid alternative [ J ].Toxicol Lett, 2001,120 ( 1 - 3 ) : 379-384.
  • 6Srinivas PR, Kramer BS, Srivastava S. Trends in biomar- ker research for cancer detection [ J ]. Lancet Oncol, 2002,2( 11 ) :698-704.
  • 7Tanaka S, Sakai A, Kimura K, et al.Proteomic analysis of the basic proteins in 5-fluorouracil resistance of human colon cancer cell line using the radical-free and highly reducing method of two-dimensional polyacrylamide gel electrophoresis[ J].Int J Oncol, 2608,33(2) :361-370.
  • 8Schwamborn K, Krieg RC, Grosse J, et al.Serum proteomic profiling in patients with bladder cancer [ J ]. Eur Urol, 2009,56(6) :989-997.
  • 9A1-Ruwaili JA, Larkin SE,Zeidan BA, et al.Discovery of serum protein biomarkers for prostate cancer progression by proteomic analysis [ J ]. Cancer Genomics Proteomics, 2010,7(2) :93-103.
  • 10Rodriguez-Pifieiro AM, Blanco-Prieto S, Sdnchez-Ote- ro N,et al. On the identification of biomarkers for non- small cell lung cancer in serum and pleural effusion[ J]. J Proteomies, 2010,73 (8) : 1511-1522.

二级参考文献8

  • 1MORTZ E, KROGH T N, VORUM H, et al. Improved silver staining protocols for high sensitivity protein identification using matris-assisted laser desorption/ionization-time of flight analysis[J] Proteomics, 2001, 1(11): 1359-1363.
  • 2MERCHANT M, WEINBERGER SR. Recent advancements in surface-enhanced laser desorption/ionozation-time of flight-mass spectrimetry[J]. Electrophoresis, 2000, 1(4): 1164-1177.
  • 3HARPER R G, WORKMAN S R, SCHUETZNER S, et al. Low-molecular-weight human serum proteome using ultrafiltration, isoelectric focusing, and mass spectrometry[J]. Electrophoresis, 2004, 25(9): 1299-1306.
  • 4ADKINS JN, VARNUM SM, AUBERRY KJ, et al. Toward a human blood serum proteome: analysis bymulti2 dimensional separation coupled with mass spectrometry[J]. Mol Cell Proteomics, 2002, 1(12): 947-955.
  • 5PIEPER R, SU Q, GATLIN C L, et al. Component immunoaffinity subtraction chromatography: an inn vative step towards a comprehensive survey of the human plasma proteome [J]. Proteomics, 2003, 3(4): 422-432.
  • 6XIAO Z, CONRADS T P, LUCAS D A, et al. Direct ampholyte-free liquid-phase isoelectric peptide focusing: application to the human serum proteome[J]. Electrophoresis, 2004, 25(1): 128-133.
  • 7JIN WH, DAI J, LI S J, et al. Human plasma proteome analysis by multidimensional chromatography prefractionation and linear ion trap mass spectrometry identification[J]. J-Proteome-Ras, 2005, 4(2): 613-619.
  • 8李雪华,李欣,丁彦青.血清蛋白质组双向凝胶电泳技术的建立[J].中国现代医学杂志,2004,14(11):95-96. 被引量:9

共引文献2

同被引文献14

  • 1李占武,马素芳,史光军,胡义利.血清补体在肝癌诊断中的价值[J].华北煤炭医学院学报,2001,3(2):141-142. 被引量:2
  • 2李祖国,赵亮,刘莉,丁彦青.结直肠癌转移动物模型血清中几种蛋白变化的观察[J].中华病理学杂志,2007,36(1):48-52. 被引量:4
  • 3He X X, Chen K, Yang J, et al.Macrophage migration inhibitory factor promotes colorectal cancer[J].Mol Med, 2009, 15 ( 1-2 ): 1-10.
  • 4Tanaka S, Sakai A, Kimura K, et al.Proteomic analysis of the basic proteins in 5-fluorouracil resistance of human colon cancer cell line using the radical-free and highly reducing method of two-dimensional polyacrylamide gel electrophoresis[J].Int J Oncol, 2008, 33 ( 2 ) : 361-370.
  • 5Rodr i guez-Pifieiro A M, Blanco-Prieto S, S 6 nchez-Otero N, et at.On the identification of biomarkers for non-small cell lung cancer in serum and pleural effusion[J].J Proteomice, 2010, 73 ( 8 ) : 1511- 1522.
  • 6Zinkin N T, Grail F, Bhaskar K, et at.Serum pro/comics and biomarkers in hepatocellular carcinoma and chronic liver disease[J].Clin Cancer Res, 2008, 14 ( 2 ) : 470-477.
  • 7Kojima T, Yoshikawa K, Saga S, et al.Detection of elevated proteins in peritoneal dissemination of gastric cancer by analyzing mass spectra data of senml proteins[J].J Surg Res, 2009, 155 ( l ) : 13-71.
  • 8Bhatti R A, Gadarowski J J.Metastatie behavior of prostatic tumor as influenced by the hematopoietic and hematogenous faetors[J].Tumour Biol, 1997, 18 (1): 1-5.
  • 9Gonsalves A, Esterni B, Bertucci F, et al.Postoperative serum proteomic profiles may predict metastatic relapse in high-risk primary breast cancer patients receiving adjuvant chemotherapy[J].Oncogene, 2006, 25 ( 7 ) : 981-989.
  • 10Langlois M R.Biological and clinical significance of haptoglobin polymorphism in humans[J].Clin Che, 1996, 42 (10) : 1589- 1600.

引证文献1

二级引证文献2

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部