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研究生:張芳瑜
研究生(外文):Fang-Yu Chang
論文名稱:利用質譜技術與計算蛋白質體學來尋找大腸直腸癌的生物標記與診斷方法
論文名稱(外文):Colorectal Cancer Detection by Mass Spectrometry and Computational Proteomics
指導教授:巫坤品
指導教授(外文):Kun-Pin Wu
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:生物醫學資訊研究所
學門:工程學門
學類:生醫工程學類
論文種類:學術論文
論文出版年:2009
畢業學年度:97
語文別:中文
論文頁數:65
中文關鍵詞:大腸癌資料探勘支持向量機生物標記
外文關鍵詞:Colorectal CancerMachine learningsupport vector machinebiomarker
相關次數:
  • 被引用被引用:1
  • 點閱點閱:308
  • 評分評分:
  • 下載下載:52
  • 收藏至我的研究室書目清單書目收藏:0
大腸直腸癌為世界排名第三高發生率及致死率的癌症 ({Bitarte:2007),而目前尚未有高準確率的生物標記出現。此研究中,我們利用 LC-MS/MS 技術,嘗試找尋可能的大腸癌生物標記,樣本為 29 位病人的癌組織及周圍正常組織,共 58 個樣本。此研究分成兩個部分,第一部分為生物標記的找尋(Gain ratio);第二部分為利用支持向量機 (support vector machine, SVM) 建置診斷樣本為癌組織或是周圍正常組織的模型。在此研究中利用資料探勘的概念去處理樣本資料,先將資料分成訓練組(45個樣本)與測試組(13個樣本),訓練組利用資料探勘中找尋特徵的演算法:Gain ratio 找出可能為生物標記的蛋白質,再利用這些蛋白質建立可以區分癌組織及周圍正常組織的模型(SVM)。而測試組用於測試模型的準確度與穩定性,用前十名表現量上升的蛋白質所建置出來的模型其準確率可以達到 100%。除此之外,利用 Box-and-Whisker Plot,Wilcoxon rank sum test,及 Principle component analysis (PCA) 驗證可能為生物標記的蛋白質。在這些蛋白質中有 3 個蛋白質在文獻中提過與大腸直腸癌有關 (CEACAM5, CEACAM6, OGN),而其他蛋白質也與疾病和發炎有關。
Colorectal cancer is one of the most common cancers and is highly fatal. To date, no biomarkers could provide accurate detection for clinical use. In this study, we identified potential biomarkers using LC-MS/MS and analyzed data by computational approaches. Data consist of 58 samples from tumor and adjacent normal tissues of 29 patients. We separated data into training and blind data sets. Our training set (45 samples) were processed to discover potential biomarkers using Gain Ratio, a kind of feature selection methods, and then the potential biomarkers were used as features to build a support vector machine (SVM) model as validation and then for the prediction of tumor and adjacent normal tissues. Blind data sets (13 samples) were used to evaluate sensitivity and specificity of the constructed model. We used Box-and-Whisker Plot, Wilcoxon rank sum test, and principle component analysis (PCA) to verify the discriminating power of selected biomarkers. In our potential biomarker list, three proteins (CEACAM5, CEACAM6, and OGN) have been reported in the previous studies. For diagnosis, when using seven to 10 markers as features, our SVM model receives 100% sensitivity and specificity on the blind test set (13 samples).
第一章 緒論
1.1大腸直腸癌簡介
1.2大腸直腸癌的檢驗
1.3研究動機與目的
1.4 Colorectal cancer (CRC) 目前所使用的找尋生物標記方法
第二章 樣本與實驗方法
2.1 樣本來源與資訊
2.2 實驗流程
第三章 資訊分析流程
3.1 流程
3.2 資料的隨機分組方法
3.3 生物標記的找尋
3.3.1 Feature Selection: Gain ratio
3.3.2 利用加權的方式整合蛋白質
3.3.3 統計分析結果
3.3.3.1 Box-and-Whisker Plot
3.3.3.2 Wilcoxon Rank Sum Test
3.3.4 利用Principle Component Analysis (PCA) 驗證篩選出的蛋白質
3.4 分類: Support vector machine (SVM)
第四章 結果
4.1生物標記找尋結果
4.1.1 Feature Selection: Gain ratio
4.1.2 Ranking Proteins by Weighted Sum
4.1.3 統計分析結果
4.1.3.1 Box-and-Whisker Plot
4.1.3.2 Wilcoxon Rank Sum Test
4.1.4 Principle Component Analysis
4.2分類
第五章 討論
參考文獻
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AmericanCancerSociety Cancer Facts Figures American Cancer Society, 2009

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Baran, A. A.; Silverman, K. A.; Zeskand, J.; Koratkar, R.; Palmer, A.; McCullen, K.; Curran, W. J., J.; Edmonston, T. B.; Siracusa, L. D. & Buchberg, A. M. The modifier of Min 2 (Mom2) locus: embryonic lethality of a mutation in the Atp5a1 gene suggests a novel mechanism of polyp suppression Genome Res, 2007, 17, 566-76

Bitarte, N.; Bandres, E.; Zarate, R.; Ramirez, N. & Garcia-Foncillas, J. Moving forward in colorectal cancer research, what proteomics has to tell World J Gastroenterol, 2007, 13, 5813-21

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Duxbury, M. S.; Ito, H.; Zinner, M. J.; Ashley, S. W. & Whang, E. E. CEACAM6 gene silencing impairs anoikis resistance and in vivo metastatic ability of pancreatic adenocarcinoma cells Oncogene, 2004, 23, 465-73

Fukuda, M.; Kanno, E. & Yamamoto, A. Rabphilin and Noc2 are recruited to dense-core vesicles through specific interaction with Rab27A in PC12 cells J Biol Chem, 2004, 279, 13065-75

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