- 學位論文
探討脂質載運蛋白-2在腎臟癌的角色及臨床意義
Research on roles and clinical significance of Lipocalin-2 in human renal cancer
摘要
腎細胞癌（Renal cell carcinoma, RCC）是成年人中最常見的腎臟癌類型，約占80％。腎癌患者不一定會有症狀，通常發現症狀時表示腫瘤已侵犯到鄰近的器官或已有遠端轉移。因此，它是泌尿生殖系統癌症中死亡率最高的癌症類型，其發生率持續上升。脂質載運蛋白-2（lipocalin-2, LCN2）是25 kDa的蛋白質，屬於脂質運載蛋白家族的成員之一，能藉由與螯鐵蛋白結合而參與細胞鐵離子的運送，並參與腫瘤形成及轉移作用，目前被學者們認為是最有潛力成為未來早期診斷急性腎損傷的生物標記。但是目前對於LCN2在腎臟癌的角色和功能仍是未知。因此本實驗建構出表現LCN2之基因載體模式來當作研究工具，以進一步探討LCN2對人類腎癌的影響。我們評估了在四種腎臟癌細胞和正常腎小管細胞HK2之內生性LCN2表現量，發現腎癌細胞LCN2 mRNA表現量低於正常腎小管細胞。更進一步地，透過分析美國癌症基因體圖譜計畫資料庫，評估血液中LCN2濃度與腎臟癌患者總存活率以及腎癌組織和正常組織中LCN2 mRNA的表現量，分析結果發現血液中LCN2濃度較低之腎臟癌患者的預後較差及腎癌組織中LCN2 mRNA表現量低於正常組織。這些結果顯示，LCN2在人類腎臟癌中可能是扮演抑制腫瘤的角色，但是其相關分子作用機制仍需更進一步的實驗來證明。未來希望能進一步確立LCN2在腎癌的角色及生物功能，並且蒐集較大量的臨床數據來研究評估LCN2是否為可信賴的診斷與預後之生物指標。
並列摘要
Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults, responsible for approximately 80 % of the cases. Besides, it has the highest mortality rate of the genitourinary cancers and its incidence has risen steadily. Lipocalin-2 (LCN2) / neutrophil gelatinase-associated lipocalin (NGAL) is an iron-sequestering protein in the antibacterial innate immune response. And the LCN2 expression is induced under various pathophysiological conditions. It is also known as an early marker of kidney injury. Although the main function of LCN2 is still unexplored, many studies confirmed its significant role in the initiation, progression, and metastasis of various types of cancer. This study was aimed to set up an expression system in RCC cell lines for the purpose of conducting further investigation into the biological properties of LCN2. We determined the expression of LCN2 in four RCC cell lines and normal kidney HK2 cells. Furthermore, by using TCGA database, we also evaluated the overall survival of RCC patients with lower and higher LCN2 expression in blood, and LCN2 mRNA levels in RCC tumors and normal samples. We found that LCN2 mRNA level is reduced in four RCC cell lines than normal kidney cells. In addition, we also discovered LCN2 expression level is lower in RCC tumors compared with normal kidney tissues, and patients with lower LCN2 expression in blood predicts worse prognosis in RCC. These findings indicated that LCN2 might be a candidate tumor suppressor in RCC. However, further studies are required to explore the detailed biological functions and molecular mechanisms involved in RCC progression.