TP53突變對具有EGFR突變的非小細胞肺癌患者帶來的影響

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李怡璇(Yi-Xuan Li) 查詢紙本館藏

畢業系所

系統生物與生物資訊研究所

論文名稱

TP53突變對具有EGFR突變的非小細胞肺癌患者帶來的影響
(Role of TP53 Mutations in EGFR-Mutated Patients Treated with Tyrosine Kinase Inhibitors)

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摘要(中)

肺癌是全世界常見的致死性癌症。肺癌主要分為小細胞肺癌和非小細胞肺癌。已知諸如吉非替尼，阿法替尼和奧西替尼等靶向表皮生長因子受體（EGFR）的酪氨酸激酶抑製劑（TKI）在具有EGFR突變的NSCLC患者中具有顯著療效。不幸的是，大多數患者會在八到十二個月內出現獲得性耐藥。對EGFR-TKIs的耐藥性一直是肺癌治療中的緊迫問題。此外，p53抑癌基因也是肺癌中經常突變的基因。這項研究旨在調查p53對TKI治療的作用。
這項研究分析了可從癌症基因組圖譜（TCGA）數據庫獲得的NSCLC數據，以及來自台中榮民總醫院的66種NSCLC臨床數據。該研究使用t檢驗，卡方檢驗和Kaplan-Meier生存曲線來分析和討論數據之間的生存差異。 Kaplan-Meier生存曲線分析表明，外顯子2、4和6中TP53突變亞組的預後顯著不同。

摘要(英)

Lung cancer is a common and lethal cancer worldwide. Lung cancer is mainly divided into small cell lung cancer and non-small cell lung cancer. The epidermal growth factor receptor (EGFR)-targeting tyrosine kinase inhibitors (TKIs) like gefitinib, afatinib, and osimertinib are known to have significant efficacy at NSCLC patients with EGFR mutation. Unfortunately, most patients develop acquired resistance within eight to twelve months. Resistance to EGFR-TKIs has been an urgent issue in the treatment of lung cancer.In addition, the p53 tumor suppressor gene is also a frequently mutated genes in lung cancer. This study is aimed to investigate the effect of p53 on treatment of TKI.
This study analyzes the NSCLC data available from The Cancer Genome Atlas (TCGA) database and 66 NSCLC clinical data from the Taichung Veterans General Hospital. The study used t-test, chi-square test and Kaplan-Meier survival curve to analyze and discuss the difference in survival between data. Furthermore, Kaplan-Meier survival curve analysis showed that the prognosis of the subgroup of TP53 mutations in exon 2、4 and 6 was significantly different.

關鍵字(中)

★ 非小細胞肺癌
★ 肺癌
★ 酪氨酸激酶抑製劑

關鍵字(英)

★ TP53
★ EGFR
★ Tyrosine Kinase Inhibitors
★ EGFR-TKI
★ afatinib
★ T790M

論文目次

中文摘要 i
Abstract ii
致謝 iii
目錄 iv
圖目錄 v
表目錄 vi
一、緒論 - 1 -
1-1 非小細胞肺癌 - 1 -
1-2 非小細胞肺癌肺癌病因 - 2 -
1-3 酪氨酸激酶抑製劑 - 3 -
1-3 T790M突變 - 5 -
1-4 TP53突變 - 6 -
1-5研究動機與目的 - 8 -
二、研究材料與方法 - 9 -
2-1研究材料 - 9 -
2-1-1肺癌患者資料- 9 -
2-1-2癌症基因體圖譜（The Cancer Genome Atlas, TCGA）- 9 -
2-2研究方法 - 10 -
2-2-1分析環境與套件 - 10 -
2-2-2 TP53突變篩選和分類 - 10 -
2-2-3統計分析 - 11 -
三、結果 - 12 -
3-1患者特徵 - 12 -
3-2 TP53突變與患者特徵之間的關係 - 16 -
3-3 TCGA上肺腺癌患者與TP53突變之間的關係 - 18 -
3-4 TP53突變位點和對TKI的反應 - 23 -
3-5 TP53突變類型和對TKI的反應 - 30 -
3-6 TP53多點突變和對TKI的反應 - 32 -
四、討論 - 33 -
五、結論 - 35 -
六、參考文獻 - 36 -
七、附錄表 - 40 -

參考文獻

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指導教授

許藝瓊(Yi-Chiung Hsu)

審核日期

2020-8-24

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