大腸直腸癌遠端轉移之血漿生物標誌及其應用PLASMA MARKER FOR DISTAL METASTASIS IN COLORECTAL CANCER

專利類型

發明

專利國別 (專利申請國家)

中華民國

專利申請案號

101112629

專利證號

I 444386

專利獲證名稱

大腸直腸癌遠端轉移之血漿生物標誌及其應用PLASMA MARKER FOR DISTAL METASTASIS IN COLORECTAL CANCER

專利所屬機關 (申請機關)

長庚大學

獲證日期

2014/07/11

技術說明

本發明係關於利用分泌型gelsolin (又稱為血漿型gelsolin，以下簡稱 pGSN) 做為一種判斷大腸直腸癌是否發生遠端轉移之方法。本發明利用 pGSN 所獨有之胺基酸序列製備出能專一性偵測 pGSN 之多株抗體，並以此自製抗體發展出高專一性酵素聯結免疫分析法 (ELISA)。使用此抗體及 ELISA 針對 pGSN 於大腸直腸癌病患組織及血漿樣品進行定量實驗，我們發現(i)相較於正常鄰近上皮細胞，pSGN 會於腫瘤細胞中過度表現；(ii)以同一位大腸直腸癌病患為研究對象，當大腸直腸癌病程進展至遠端轉移時，病人之血漿中之 pGSN 會明顯增加；若同時結合量測大腸直腸癌病人血漿中的腫瘤癌胚抗原(carcinoembryonic antigen, CEA) 與 pSGN 含量數據，可較單獨使用 CEA 做為判斷大腸直腸癌病人是否發生遠端轉移病灶的偵測效力為高；(iii) pSGN 含量在第四期病人血漿中較第一~三期病人血漿中顯著上升；及(iv) pSGN 可調節大腸直腸癌細胞株的移動功能。據此，我們提出製備此專一性偵測 pGSN 多株抗體及使用 pGSN 做為一種血漿生物標誌用以判斷大腸直腸癌是否發生遠端轉移之新穎有效方法。 關鍵字：secretory gelsolin、大腸直腸癌、腫瘤遠端轉移、血漿生物標誌 This invention is a method for the detection of distal metastasis in colorectal cancer (CRC) patients using secretory gelsolin (pGSN). Polyclonal antibodies specifically against pGSN, but not cytoplasmic form of gelsolin, were produced and applied to develop an ELISA for measuring the pSGN levels in CRC patients. Using the antibodies and ELISA, we found that (i) pGSN was highly overexpressed in CRC tissue specimens compared to adjacent normal tissues; (ii) pSGN levels increased in plasma samples from CRC patients that developed distal metastasis after surgery than those from the same patients without distal metastasis and before surgery; the combination of pSGN and carcinoembryonic antigen (CEA) had a higher diagnostic efficacy than the use of CEA alone for detecting metastatic disease in CRC patients; (iii) a significant increase of pSGN in plasma samples of stage IV versus stage I-III CRC patients before treatment; and (iv) pSGN is involed in regulating CRC cell migration.

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