瀏覽人氣：1,687

蔡國旺 主任

最高學歷：國防醫學院生命科學研究所博士

研究領域：癌症基因體、 生物標記開發、腫瘤生物學

分機：5796

電子信箱：tch33225@tzuchi.com.tw

https://orcid.org/0000-0002-9028-9834

  • 微型核糖核酸在癌症轉移過程中的角色
  • 長片段非編碼核糖核酸在癌症轉移過程中的角色
  • 長鏈非編碼核糖核酸與腫瘤微環境的角色
  • 長鏈非編碼核糖核酸於腫瘤能量代謝之角色

近年來人類基因體計畫加速進展，基因體學研究成為目前熱門研究課題，而高通量次世代定序分析成為當前不可或缺的分析技術，另外;真核細胞的轉錄後調控對其基因表達是一項相當重要的步驟，目前已知許多疾病以及癌細胞的產生與轉移（metastasis）與抗藥(drug resistance)，都與DNA-RNA-Protein之間的調控有著密切的關係。利用高通量的次世代定序可以快速解析細胞中的DNA變異、DNA表觀遺傳、RNA表現圖譜甚至RNA的後修飾等等，近年本研究室已運用次世代定序完成NGS-Based Cancer Panels定序、RNA transcriptome Profile、small RNA profiles、lncRNA RNA profiles以及16S rRNA  metagenomics sequence等等進行探討人類疾病的成因以及開發生物標記。目前本研究室利用次世代基因定序儀，積極開發分子診斷標記，短期目標此儀器將會被運用在基因突變、微型核糖核酸轉錄體異常、腸胃道細菌分析，希望了解哪些基因體上發生異常改變?如此將有助於了解疾病的致病機轉，並且提供作為臨床上的治療與診斷依據。

非編碼核醣核酸:

    近幾年發現細胞內大量存在小片段RNA，稱之為微型核糖核酸(microRNA)，microRNA長度只有21-25個核苷酸(nucleotide)，而這些microRNA被產生後送往細胞質干擾基因表現，藉由與mRNA鍵結成雙股再將其分解消滅，目前已知道miRNA在發育過程以及各種疾病都扮演著重要的角色，而miRNA跟一般基因不同，miRNA靠調控其標的基因來執行功能，近幾年來研究發現miRNA與很多疾病息息相關，因此目前也積極運用生物資訊方式預測可能性較高的標的基因，最後再結合傳統實驗進一步確認。

癌症分子標記:

    台灣癌症發生率逐年增加，每年因罹癌而死亡的人數高居不下，在臨床上化療合併放射線治療是主要治療侵襲性癌的策略之一，其作用機制為利用放射線導致癌細胞中的DNA 斷裂，達到促使癌細胞生長停止並走向死亡的路徑，臨床上發現有一些病人對於化療、放射線治療有很好的療效，相反的也有另外一群人對於化療、放射線治療反應非常差且癒後不良，然而治療的效果好壞與其細胞內部某些基因表現以及訊息傳遞異常有關，本研究團隊短期目標希望尋找可預測癌症病患對於放射線治療反應的生物標記，長期目標希望開發一些分子藥物可以促進放射線治療的效果，期許我們的研究成果可提供作為評估病患是否要接受放射線治療或改變治療策略的依據。

非編碼核糖核酸在人類癌症轉移與抗藥性的轉譯醫學運用

研究方向簡述:

癌轉移以及抗藥性往往導致癌症治療失敗，而細胞內非編碼核糖核酸(microRNA以及lncRNA)表現失調或突變被證實與腫瘤發展息息相關，本研究團隊發現非編碼核糖核酸可以透過外分泌調控周邊腫瘤微環境重編程，利用偵測非編碼核糖核酸表現量亦可做為腫瘤診斷與預後評估的生物標記，並且分別從表觀遺傳、轉錄體調控以及SNP等不同層面，證實非編碼核糖核酸在癌症的轉移與抗藥性扮演關鍵角色，目前也積極利用天然藥物與小分子藥物調控非編碼核糖核酸表現，作為毒殺癌細胞以及提高免疫治療效果之策略。綜合以上下圖所示:本研究團隊主要專注非編碼核糖核酸涉在癌症進展的三大領域中的角色，主題一:研究ncRNA調控腫瘤微環境的重編程，包括:影響巨噬細胞、毒殺T細胞的浸潤以及巨噬細胞M1/M2的polarization；目標二:研究ncRNA在腫瘤細胞能量代謝路徑的角色，特別是周邊脂肪細胞如何透過exosome影響腫瘤細胞代謝重編程；目標三:研究ncRNA在腫瘤轉移、生長以及死亡過程扮演的角色，特別是目前新穎的ferroptosis死亡路徑。短期目標利用細胞模式在in vitro下釐清ncRNA在這三大領域中的可能角色，中期目標利用台北慈濟生物資料庫組織檢體進行in vivo驗證，並且分析ncRNA作為診斷以及預後生物標記的可能性；最終希望利用中草藥或小分子藥物針對ncRNA開發治療腫瘤的新穎藥物。

(A) SCI Papers

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  10. Lin JT, Tsai KW: Circulating miRNAs Act as Diagnostic Biomarkers for Bladder Cancer in Urine. Int J Mol Sci 2021, 22(8).
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  30. Huang LH, Lin PH, Tsai KW, Wang LJ, Huang YH, Kuo HC, Li SC: The effects of storage temperature and duration of blood samples on DNA and RNA qualities. PloS one 2017, 12(9):e0184692.
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  35. Tseng HW, Shiue YL, Tsai KW, Huang WC, Tang PL, Lam HC: Risk of skin cancer in patients with diabetes mellitus: A nationwide retrospective cohort study in Taiwan. Medicine 2016, 95(26):e4070.
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  50. Pan CT, Tsai KW, Hung TM, Lin WC, Pan CY, Yu HR, Li SC: miRSeq: a user-friendly standalone toolkit for sequencing quality evaluation and miRNA profiling. BioMed research international 2014, 2014:462135.
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  66. Li SC, Liao YL, Chan WC, Ho MR, Tsai KW, Hu LY, Lai CH, Hsu CN, Lin WC: Interrogation of rabbit miRNAs and their isomiRs. Genomics 2011, 98(6):453-459.
  67. Li SC, Chan WC, Lai CH, Tsai KW, Hsu CN, Jou YS, Chen HC, Chen CH, Lin WC: UMARS: Un-MAppable Reads Solution. BMC bioinformatics 2011, 12 Suppl 1:S9.
  68. Ho MR, Tsai KW, Chen CH, Lin WC: dbDNV: a resource of duplicated gene nucleotide variants in human genome. Nucleic acids research 2011, 39(Database issue):D920-925.
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  74. Tsai KW, Tarn WY, Lin WC: Wobble splicing reveals the role of the branch point sequence-to-NAGNAG region in 3′ tandem splice site selection. Molecular and cellular biology 2007, 27(16):5835-5848.
  75. Tsai KW, Lin WC: Quantitative analysis of wobble splicing indicates that it is not tissue specific. Genomics 2006, 88(6):855-864.

(B) 專書

  1. M. Leung#,K. W. Tsai# and H. W. Pan. DNA Methylation in Aggressive Gastric Cancer . InTech. Oct, 2012.
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(C) Patent

  1. 【中文發明名稱】生物標記用以診斷第二型雙極症的用途 (專利局審查中)
  2. 【中文發明名稱】生物標記用以診斷川崎氏症的用途 (專利局審查中)

台北慈濟醫院：

一般外科：張耀仁副院長、張健輝 醫師

大腸直腸科：呂宗儒 醫師

病理檢驗科：曾暉華 醫師、胡萬炯醫師

小兒科：鄭敬楓 副院長

中醫：呂秉勳 醫師

 

院外合作機構：

中央研究院 生醫所：林文昌 教授

台北醫學大學：閻雲 院士

花蓮慈濟大學：張新侯 教授

高雄長庚醫院：李松洲 研究員

高雄榮民總醫院：楊宜芳 博士

中央大學：許藝瓊 教授