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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/99941完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 周涵怡 | zh_TW |
| dc.contributor.advisor | Han-Yi Elizabeth Chou | en |
| dc.contributor.author | 鍾曜宇 | zh_TW |
| dc.contributor.author | Yao-Yu Chung | en |
| dc.date.accessioned | 2025-09-22T16:04:52Z | - |
| dc.date.available | 2025-09-23 | - |
| dc.date.copyright | 2025-09-22 | - |
| dc.date.issued | 2025 | - |
| dc.date.submitted | 2025-07-17 | - |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/99941 | - |
| dc.description.abstract | 口腔癌是全球常見癌症之一，具有高度侵襲性及轉移性，使早期診斷及有效治療成為迫切的研究議題。儘管標靶治療因其高準確性與低副作用逐漸成為癌症治療的重要方向，目前口腔癌治療僅核准少數標靶藥物，且對於靶點蛋白表現不明顯的患者療效有限，因此必須發掘新穎的治療標靶。本研究結合公開單細胞RNA定序資料集分析以及本實驗室先前研究之長期酸化環境對口腔癌細胞影響之成果，透過蛋白質層級的表現量化驗證，探索口腔癌新穎治療標靶及其可能的分子調控機制。研究結果指出，INHBB於口腔癌組織中具有顯著較高的表現比例，且其表現強度與臨床分期高度相關，顯示INHBB具有作為早期診斷及預後評估的潛力，亦透過單細胞RNA定序分析，了解腫瘤微環境中細胞間通訊與高INHBB表達癌細胞之差異表達基因與上游調控因子，並提出假設性腫瘤酸化微環境與INHBB調控模型，為癌症靶點探索提供了新的研究方向。 | zh_TW |
| dc.description.abstract | Oral squamous cell carcinoma (OSCC) ranks among the most prevalent malignancies worldwide and is characterized by pronounced invasiveness and metastatic potential, rendering early diagnosis and effective therapy essential. Although targeted treatments provide high specificity with relatively low toxicity, only a few have been approved for OSCC, and their efficacy is restricted in tumors lacking strong expression of the relevant molecular targets, highlighting the need for novel therapeutic candidates. By integrating single-cell RNA sequencing with prior evidence on the effects of chronic extracellular acidification in OSCC cells and validating findings at the protein level, potential targets and their regulatory mechanisms were interrogated. INHBB was identified as markedly overexpressed in OSCC tissues, with expression intensity strongly correlated with clinical stage, suggesting value as both an early diagnostic biomarker and a prognostic indicator. Single-cell analyses further elucidated cell–cell communication networks, differentially expressed genes, and upstream regulators associated with INHBB-high malignant cells. On this basis, a working hypothesis model is proposed in which an acidified tumor microenvironment modulates INHBB expression, providing a conceptual framework for future target discovery in OSCC. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2025-09-22T16:04:52Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2025-09-22T16:04:52Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 謝辭 i
摘要 ii Abstract iii Contents v List of Figures viii List of Tables xiii Chapter 1 Introduction 1 1.1 Clinical Burden and Unmet Needs in OSCC 1 1.2 Current Limitations of Targeted Therapies in OSCC 2 1.3 Single-cell Transcriptomics in Cancer Research 3 1.4 Insights from scRNA-seq in OSCC 4 1.4.1 Intratumoral Heterogeneity and EMT-Associated States 4 1.4.2 Immune Landscape and Prognostic Cell Subsets 5 1.4.3 Metastatic Adaptation and Chemotherapy Resistance 5 1.5 Integrative Strategies for Target Discovery 6 1.6 Inhibin Beta B 7 1.7 Aim of the Study 8 1.8 Study Significance 8 Chapter 2 Materials and methods 10 2.1 Histological Staining 10 2.1.1 Tissue Microarrays 10 2.1.2 Immunohistochemistry (IHC) 10 2.2 Processing of IHC Image 11 2.2.1 Image Acquisition 11 2.2.2 Image Quantification 12 2.3 Acquisition and Processing of Transcriptome Data 12 2.4 Analysis of Transcriptome Data 13 2.4.1 GO and KEGG Pathway Enrichment 13 2.4.2 Cell–Cell Communication Analysis 14 2.4.3 Transcription Factor Enrichment Analysis 14 2.5 Statistical Analysis 14 Chapter 3 Results 15 3.1 Expression of INHBB Protein in OSCC 15 3.1.1 Diagnosis Distribution of TMA 15 3.1.2 IHC Characterization 16 3.1.3 Comparison of INHBB Expression Between Normal and OSCC Tissues 16 3.1.4 Comparison of INHBB Expression with Sex 18 3.1.5 Comparison of INHBB Expression with Age (<65 vs. ≥65) 20 3.1.6 Comparison of INHBB Expression with Clinical Stages 22 3.1.7 Comparison of INHBB Expression with T Status 24 3.1.8 Comparison of INHBB Expression with N Status 26 3.2 Association of INHBB Expression with Clinical Characteristics 28 3.3 Expression of Menin Protein in OSCC 31 3.4 scRNA-seq Dataset Characteristics 32 3.4.1 UMAP Projection and Cell Type Annotation 32 3.4.2 Cell Type Composition Across Samples 37 3.5 Differential Expression Genes in OSCC 39 3.5.1 Differential Expression Between Malignant and Non‑malignant Cells 39 3.5.2 Differential Expression Between Metastatic and Primary OSCC Cells 42 3.6 INHBB Gene Expression in scRNA-seq Database 47 3.6.1 Differential Gene Expression in INHBB-high Malignant Cells 48 3.6.2 Transcriptional Factors of Differentially Expressed Genes in INHBB-high Malignant Cells 50 3.6.3 Differential Gene Expression in INHBB-high Endothelial Cells 52 3.6.4 Differential Gene Expression in INHBB-high Fibroblasts 55 3.7 Cell Interaction in scRNA-seq Datasets 55 3.7.1 MIF Signaling 56 3.7.2 GALECTIN Signaling 62 3.7.3 SPP1 Signaling 62 3.7.4 VISFATIN (NAMPT) Signaling 64 Chapter 4 Discussion 66 Chapter 5 Conclusion 69 References 70 | - |
| dc.language.iso | zh_TW | - |
| dc.subject | 單細胞分析 | zh_TW |
| dc.subject | 口腔癌 | zh_TW |
| dc.subject | menin | zh_TW |
| dc.subject | INHBB | zh_TW |
| dc.subject | 轉錄體 | zh_TW |
| dc.subject | transcriptome | en |
| dc.subject | INHBB | en |
| dc.subject | menin | en |
| dc.subject | single cell analysis | en |
| dc.subject | oral cancer | en |
| dc.title | 口腔癌新穎靶點探索的轉錄體整合分析：聚焦於 INHBB | zh_TW |
| dc.title | Integrative Transcriptomic Analysis for Target Identification in OSCC: Spotlight on INHBB | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 113-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 李財坤;郭彥彬 | zh_TW |
| dc.contributor.oralexamcommittee | Tsai-Kun Li;Mark Yen-Ping Kuo | en |
| dc.subject.keyword | 口腔癌,單細胞分析,轉錄體,INHBB,menin, | zh_TW |
| dc.subject.keyword | oral cancer,single cell analysis,transcriptome,INHBB,menin, | en |
| dc.relation.page | 83 | - |
| dc.identifier.doi | 10.6342/NTU202501806 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2025-07-18 | - |
| dc.contributor.author-college | 醫學院 | - |
| dc.contributor.author-dept | 口腔生物科學研究所 | - |
| dc.date.embargo-lift | N/A | - |
| 顯示於系所單位： | 口腔生物科學研究所 | |
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