乳癌組織中免疫細胞的反應對於東西方人之預後影響

Different survival impact of immune cell composition of breast cancer between east Asian countries and western countries

陳敬軒(Ching-Hsuan Chen)

指導教授 ： 盧子彬

國立臺灣大學/公共衛生學院/流行病學與預防醫學研究所/碩士(2018年)

https://doi.org/10.6342/NTU201800110

摘要

亞洲人與西方人的乳癌有著不同的臨床病理特徵與存活機率。最近研究發現腫瘤組織中浸潤的免疫細胞(Tumor infiltrating immune cells)與病人存活時間有關。為了研究此免疫細胞對於東西方人預後的影響，我們從美國基因表現資料庫(GEO)下的九個資料庫與美國癌症基因體圖譜計畫(TCGA)取得病人基因表現量的資料，並使用兩種演算法計算腫瘤浸潤免疫細胞的組成與其在腫瘤中所占比率的表現分數。與西方人比起來，亞洲人有較高的免疫分數、較長的整體存活期間(Overall survival)與較長的無病存活期間(Disease free survival)。高免疫分數的乳癌病人有較佳的預後。在治療反應與免疫細胞組成方面亞洲人與西方人無顯著差異。各腫瘤浸潤免疫細胞對於整理存活期間與無病存活期間的影響在亞洲人與西方人身上略有出入。只有活化的輔助型T細胞(Activated CD4 T cell)對於東西方病人的整體存活期間與無病存活期間有顯著的正向影響。整體而言，亞洲的乳癌病人有較佳的預後；此種現象也許與較多的腫瘤浸潤免疫細胞有關。

關鍵字

免疫 ； 乳癌 ； 亞洲人

並列摘要

The differences of clinicopathological features and survival between Asian and Western breast cancer remained to be elucidated. Recent studies showed that composition of tumor infiltrating immune cells was associated with patients' survival. To evaluate survival impact of tumor infiltrating immune, two algorithms were used to infer the amount and subtypes of infiltrating immune cells from gene expression profiles, which presented as immune score and percentage of each immune cell. 9 Gene Expression Omnibus datasets and breast cancer dataset of The Cancer Genome Atlas project were included in this study. Compared with Western patients, Asian had significantly higher immune score, more favorable overall survival and disease free survival. Higher immune score was associated with a more favorable prognosis. In terms of treatment response and immune cell composition, there was no significant difference between Asian and Western. The survival impact of immune cells varies across races and survival endpoints. Only high signature of activated CD4 T cell was significantly associated with favorable prognosis in overall survival and disease free survival. In summary, Asian breast cancer patients had more favorable prognosis than Western, partly contributed by higher tumor infiltrating immune cells.

並列關鍵字

Immune ； Breast cancer ； Asian

參考文獻

1. Ferlay, J., et al., Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer, 2015. 136(5): p. E359-86.

2. Society., A.C., Breast Cancer Facts & Figures 2017-2018., I. Atlanta: American Cancer Society, Editor. 2017.

4. Lin, C.H., et al., Distinct clinicopathological features and prognosis of emerging young-female breast cancer in an East Asian country: a nationwide cancer registry-based study. Oncologist, 2014. 19(6): p. 583-91.

5. Iqbal, J., et al., Differences in breast cancer stage at diagnosis and cancer-specific survival by race and ethnicity in the United States. JAMA, 2015. 313(2): p. 165-73.

7. Mantovani, A., et al., Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol, 2002. 23(11): p. 549-55.