研究生: |
李妍蒨 Lee, Yen-chien |
---|---|
論文名稱: |
IL-6和惡性胸水肺腺癌臨床及免疫調控相關性 The clinical relationship between IL-6, immune microenvironment and malignant pleura effusion lung adenocarcinoma |
指導教授: |
蘇五洲
Su, Wu-chou |
學位類別: |
碩士 Master |
系所名稱: |
醫學院 - 臨床醫學研究所 Institute of Clinical Medicine |
論文出版年: | 2009 |
畢業學年度: | 97 |
語文別: | 英文 |
論文頁數: | 80 |
中文關鍵詞: | IL-6 、肺腺癌 、非小細胞肺癌 、酵素結合免疫吸附法 |
外文關鍵詞: | progression free survival., forkhead/winged-helix box protein P3 (FoxP3), carcinoembryonic antigen (CEA), NFAT, nuclear factor of activated T cells, PFS, white blood cell (WBC), regulatory T cells (Tregs), Enzyme Linked-Immuno-Sorbent Assay (ELISA), Non-small cell lung cancer (NSCLC), tumor-infiltrating lymphocytes (TILs) |
相關次數: | 點閱:167 下載:1 |
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目的
肺癌是癌症死亡主要原因,而非小細胞型態佔肺癌85%,初診斷即以惡性胸水來表現的病人占非小細胞肺癌的14.4%。根據之前研究,IL-6和惡性胸水的產生有關,其中細胞型態又以肺腺癌為主,而血液內IL-6濃度升高是一種不好的預後因子。台灣女性族群發生肺癌,也以肺腺癌為主要型態,這類族群預後不好。癌症細胞會表現FoxP3,或者去調控T細胞產生FoxP3,進而抑制周遭免疫細胞,幫助癌細胞生長。故了解癌症細胞周遭環境,血液內IL-6濃度高低,和臨床上病人相關性是很重要。
實驗設計
從2001到2008年, 共收集了67位惡性胸水的病人, 在治療前先抽血測血液中的白血球, 血小板,CEA,血中IL-6值,並用胸腔鏡切片,同時收集惡性胸水來分析,測胸水中IL-6值,用IHC方式,在胸膜組織用抗體染CD4+, CD8+, FoxP3+,探討和病人預後臨床相關性。
結果
血中IL-6, CEA, 白血球, 血小板值愈高預後愈不好,FoxP3數目愈多預後愈不好,CD8+T cell數目愈低預後愈不好。
結論
以單變數分析,高的血液IL-6濃度 (p=0.018), 高的血液白血球數(p<0.001), 高的血小板數(p=0.02), 和短時間第一線藥物治療失敗(p<0.01)是不好的預後因子。 多因子分析中,高的血液白血球數(p<0.005), 和短時間第一線藥物治療失敗(p<0.01)是不好的預後因子。
Purpose
Lung cancer is the leading cancer-related death in Taiwan and worldwide and NSCLC accounted about 85% of lung cancer. Among NSCLC patients, those with pleural effusion at the time of initial diagnosis accounted for 14.4%. IL-6 had been implicated to be the possible cause of malignant pleural effusion. Women in Taiwan with malignant pleural effusion are usually nonsmoker and the tissue type is usually of adenocarcinoma subtype. Elevated serum IL-6 has been implicated as poor prognosis. Cancer cells could express FoxP3. The relationships between IL-6 and FoxP3 are controversies. We wonder if there is relationship between malignant pleural effusion IL-6 level and the circulating IL-6 serum level. To clarify the possible role of serum IL-6 level and the generation of malignant pleural effusion, the study is designed. We hope the profile of immune cells in lung cancer tissue might predict overall survival. Also, the relationship between serum, pleural IL-6 levels and the clinical prognosis of the patients needed to be clarified.
Method
67 eligible patients with malignant pleural effusion came to National Chung Kung University from 2001 August 2 to 2008 Jan 3 were selected. The patients had received pleural biopsy by thoracoscopy before treatment. Pleural effusion was collected during the diagnostic thoracoscopy. Biopsy tissues were stained by immunohistochemistry of FoxP3, CD8+ and CD4+. Clinical data were collected. Serum and pleural interleukin-6 was measured by ELISA. Kaplan-Meier methods had been used for univariate analysis. Multivariate analyses were done by the Cox proportional hazards regression model.
Results
In univariate analyses, high serum IL-6 levels (p=0.018), high WBC, high platelets counts (p=0.02), and short PFS (p<0.01) correlated significantly with a worse overall survival. No such relation were noted for pleural effusion IL-6 levels , pleural CD8+, pleural CD4+, and FoxP3. In multivariate analyses, a high number of white blood cells (p=0.005) and short progression free survival (p=0.001) were independent worse prognostic factors for overall survival.
Conclusion
High WBC, short PFS had been related to worse overall survival.
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