皮膚惡性黑色素瘤中第二型人類白血球抗原表現量與疾病預後相關:以生物資訊方法系統性分析微陣列和核醣核酸序列資料庫

Expressions of HLA Class II Genes in Cutaneous Melanoma Were Associated with Clinical Outcome: Systematic Analysis of Public Microarray and RNA-Seq Datasets by Bioinformatics Approaches

陳泱伊(Yang-Yi Chen)

指導教授 ： 藍政哲

高雄醫學大學/醫學院/臨床醫學研究所碩士班/碩士(2020年)

摘要

皮膚惡性黑色素瘤是一種源於黑色素細胞的惡性腫瘤，具有高度的侵襲性與轉移能力，為皮膚癌當中造成患者死亡的最大宗。人類第二型白血球抗原(HLA)蛋白，又稱第二型主要組織相容性複合物(MHC)分子，在抗原呈遞和免疫反應的起始有重要作用。然而，目前第二型HLA基因表達情形與皮膚惡性黑色素瘤患者存活率和疾病進展之間的相關性資料有限且結果不一致。在本研究中，我們運用多種生物信息學工具，分析來自癌症基因組圖譜(TCGA)的皮膚惡性黑色素瘤的微陣列和RNA定序數據資料。生存分析顯示皮膚惡性黑色素瘤中第二型HLA 基因的表現量較高之患者有較好的總體存活率，尤其是HLA-DP和-DR基因；與其他癌症相比，第二型HLA基因的表達情形與皮膚惡性黑色素瘤的存活率最密切相關。此外，與第二型HLA共同表達之基因，包括APOL3、CD74、CTSS、CXCR3、C1QA、C1QB、ITGB2、LAPTM5、NCF1C、SLAMF8和TNFRSF1B，被發現與抗原加工、免疫反應和發炎反應相關，各基因的表現量也與皮膚惡性黑色素瘤的總體存活率成正相關。因此，研究結果提示增加第二型HLA基因的表達可促進腫瘤抗原被呈遞給免疫系統，而有助於增強對抗腫瘤的免疫反應和相關發炎反應。總結以上，我們推測第二型HLA基因的表達情形有機會作為皮膚惡性黑色素瘤預後的生物標誌和免疫療法的標的。

關鍵字

皮膚惡性黑色素瘤 ； 第二型人類白血球抗原 ； 第二型主要組織相容性複合體 ； 生物資訊學

並列摘要

Cutaneous melanoma, a malignant tumor originating from melanocytes, is an aggressive neoplasm with high metastatic potential that accounts for most of skin cancer related deaths. Human leukocyte antigen (HLA) class II molecules, also known as Major histocompatibility complex (MHC) class II molecules, play important roles in antigen presentation and initiation of adaptive immune responses. However, studies investigating the correlation between the expression level of HLA class II genes and overall survival or disease progression in cutaneous melanoma are limited and lead to contradictory results. In the present study, we analyzed microarray and RNA-sequencing data of cutaneous melanoma from The Cancer Genome Atlas (TCGA) and other public database using bioinformatics tools. Survival analysis revealed higher expression level of HLA class II genes in cutaneous melanoma, especially HLA-DP, -DR and -DO, were markedly associated with better overall survival. Furthermore, the expressions of HLA class II genes most closely associated with survival in cutaneous melanoma among 21 common cancer types. Furthermore, genes co-expressed with HLA class II genes were identified, which included APOL3, CD74, CTSS, CXCR3, C1QA, C1QB, ITGB2, LAPTM5, NCF1C, SLAMF8, and TNFRSF1B. These genes were found to be associated with antigen processing, immune response and inflammatory response. The results indicated that increased HLA class II expression may contribute to enhanced anti-tumor immunity via presenting tumor antigens to the immune cells. Therefore, HLA class II genes may serve as prognostic biomarkers and future therapeutic targets in cutaneous melanoma

並列關鍵字

cutaneous melanoma ； HLA class II ； MHC class II ； bioinformatics

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