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研究生: 陳志豪
CHEN, JHIH-HAO
論文名稱: 基於反卷積模型的多種癌症中免疫細胞組成之因果中介分析
Causal mediation analysis of immune cell composition in various cancers based on deconvolution model
指導教授: 馬瀰嘉
Ma, Mi-Chia
戴安順
Tai, An-Shun
學位類別: 碩士
Master
系所名稱: 管理學院 - 統計學系
Department of Statistics
論文出版年: 2025
畢業學年度: 113
語文別: 中文
論文頁數: 105
中文關鍵詞: CIBERSORT 演算法ESTIMATE 演算法Cox 比例風險模型中介分析Wilcoxon 排序和檢定配對T 檢定
外文關鍵詞: CIBERSORT Algorithm, ESTIMATE Algorithm, Cox proportional hazards model, mediation analysis, Wilcoxon rank-sum test,, Paired t test
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  • 癌症是全球主要死因之一,免疫細胞在腫瘤微環境中扮演著重要角色,影響腫瘤生長、轉移及治療反應。理解免疫細胞與臨床特徵及患者存活的關係對優化治療策略至關重要。本研究利用癌症基因組圖譜(TCGA)數據庫中的RNA測序數據,採用CIBERSORT演算法估算不同癌症樣本中的免疫細胞組成比例。CIBERSORT能精確解析腫瘤樣本中各種免疫細胞的比例,提供腫瘤免疫環境的詳細資訊。在估算完免疫細胞比例後,本研究使用ESTIMATE 演算法來估計腫瘤純度,並根據腫瘤純度調整免疫細胞比例,提高估算準確性,更精確地反映腫瘤微環境中的免疫狀況。
    本研究首先運用Wilcoxon排序和檢定(Wilcoxon rank-sum test)和配對T 檢定(Paired t test)比較不同癌症樣本中各類免疫細胞比例的差異,辨別不同癌症類型中的免疫細胞特徵。在存活分析方面,本研究採用Cox比例風險模型,評估免疫細胞比例對患者存活時間的影響,幫助理解特定免疫細胞類型的存在和比例如何與患者存活相關,為臨床決策提供依據。最後,透過中介分析,本研究推斷了免疫細胞比例作為中介變數,影響患者臨床特徵與存活狀態、存活時間的關係。

    Cancer is one of the leading causes of death globally, and immune cells play a crucial role in the tumor microenvironment, influencing tumor growth, metastasis, and treatment response. Understanding the relationship between immune cells, clinical characteristics, and patient prognosis is vital for optimizing treatment strategies. This study utilizes RNA sequencing data from The Cancer Genome Atlas (TCGA) database and employs the CIBERSORT algorithm to estimate the composition ratios of immune cells in different cancer samples. CIBERSORT accurately parses the proportions of various immune cells within tumor samples, providing detailed information about the tumor immune environment. After estimating the proportions of immune cells, this study further uses the ESTIMATE Algorithm to assess tumor purity and adjust immune cell proportions based on tumor purity, enhancing the accuracy of the estimations and more precisely reflecting the immune status within the tumor microenvironment.
    First, this study employs the Wilcoxon rank-sum test and Paired t test to compare the differences in immune cell proportions across various cancer samples, identifying immune cell characteristics in different cancer types. For survival analysis, this study uses the Cox proportional hazards model to evaluate the impact of immune cell proportions on patient survival time, aiding in the understanding of how the presence and proportion of specific immune cell types affect patient prognosis, providing a basis for clinical decision-making. Finally, through mediation analysis, this study infers the role of immune cell proportions as mediating variables influencing the relationship between clinical characteristics and survival status, survival time.

    摘要 III Abstract IV 目錄 XIV 表目錄 XVI 圖目錄 XVII 第一章 緒論 1 1.1 研究背景與動機 1 1.2 數據來源 2 1.3 研究目的與方法 5 1.4 研究架構 5 第二章 文獻回顧 7 2.1 基因表現反卷積演算法 7 2.1.1 反卷積介紹 7 2.1.2 CIBERSORT模型 8 2.1.3 簽名矩陣 10 2.1.4 v支持向量迴歸 11 2.2 ESTIMATE 演算法 12 2.2.1基因集富集分析 14 2.2.2單樣本基因集富集分析 15 2.3 存活分析模型 16 2.3.1 Cox比例風險模型 16 2.4 特徵選擇 17 2.4.1單變量分析 17 2.4.2 LASSO迴歸 17 2.4.3 嶺迴歸 18 2.4.4逐步迴歸 19 2.5 因果推論 19 2.5.1因果中介分析 19 2.5.2直接效應和間接效應 21 2.5.3平均因果中介效應和平均直接效應 21 2.5.4 干擾因子 22 第三章 研究方法 24 3.1 CIBERSORT 模型 27 3.2 ESTIMATE 演算法 29 3.3 相對豐度差異分析 31 3.4 存活分析模型 33 3.4.1 Cox比例風險模型 34 3.4.2風險比 35 3.5中介因子選擇 36 3.5.1單變量分析 36 3.5.2 LASSO迴歸和嶺迴歸 37 3.5.3 逐步迴歸 37 3.6因果中介分析 38 3.6.1單一中介因子之因果中介效應模型 39 第四章 實例分析 44 4.1 人口統計特徵分析結果 44 4.2 相對豐度差異分析 47 4.3 免疫細胞浸潤分析 54 4.4 因果中介之總效應模型分析 58 4.5 中介因子篩選 61 4.6 單一中介因子之因果中介效應模型 65 第五章 結論與未來展望 83 5.1 結論與未來研究方向 83 5.2建議與研究限制 84 參考文獻 85

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