| 摘要: | 胰腺癌 (PC) 是一種侵襲性癌症，症狀不明顯且死亡率高，5 年內生存率不到 11%。 到目前為止，作為胰腺癌早期臨床生物標誌物的重要基因尚未完全了解。 因此，本研究主旨在利用生物信息學和體外研究揭示胰腺癌早期階段的重要基因，並作為早期檢測的臨床生物標誌物。 我們使用癌症 RNA-Seq Nexus 數據庫並確定了一個抑癌基因 (NAGK) 和五個致癌基因（FXYD3、ACTR1A、B3GNT3、SIGIRR 和 EXOC1）在胰腺癌的早期階段具有重要意義。 在GEPIA 和 UALCAN資料庫中發現NAGK 的基因表達較低，而 FXYD3、ACTR1A、B3GNT3、SIGIRR 和 EXOC1 的基因表達較高。 Kaplan-Meier 圖顯示 NAGK 低表達和 FXYD3、ACTR1A、B3GNT3、SIGIRR 和 EXOC1 高表達的胰腺癌患者總體生存率和無病生存率較低。胰腺癌腫轉移也可以發生在早期病變中，而不是僅僅局限於已發展的原發性腫瘤。因此，將原發性胰腺癌 I 期和 II 期差異表達的六個基因與人類癌症轉移數據庫 (HCMDB) 中的轉移相關基因（1938 個基因）進行比較，得到兩個重疊基因（B3GNT3 和 FXYD3）。為了建立這兩個具有胰腺癌早期轉移特徵的特異性基因與胰腺癌細胞系遷移能力之間的表達相關性，檢測了 B3GNT3 和 FXYD3 在四種不同遷移能力的胰腺癌細胞系，包括 HPAC、BxPC-3、AsPC-1 和 PANC-1，以及正常胰管上皮細胞系 HPDE6-C7中的表達模式。結果顯示，隨著四種胰腺癌細胞系遷移能力的增強，FXYD3基因的表達量顯著增加。 因此我們將證明FXYD3在胰腺癌發生過程中的功能作用。
Pancreatic cancer (PC) is an aggressive cancer with silent symptoms and high mortality with less than 11% of the 5-year survival rate. Until now, the significant gene as clinical biomarkers in the early stages of PC have not been fully understood. Hence, this study aims to reveal the significant genes in the early stages of PC using bioinformatics and in vitro studies and to serve as clinical biomarkers for early detection. We used Cancer RNA-Seq Nexus database and identified one tumor suppressor gene (NAGK), and five oncogenes (FXYD3, ACTR1A, B3GNT3, SIGIRR, and EXOC1) are significant in the early stages of PC. The GEPIA and UALCAN predicted a low gene expression of NAGK while high gene expression of FXYD3, ACTR1A, B3GNT3, SIGIRR, and EXOC1 in the PC patients. The Kaplan-Meier plot reported that PC patients with low expression of NAGK and high expression of FXYD3, ACTR1A, B3GNT3, SIGIRR, and EXOC1 had low overall survival and disease-free survival. It has been shown that pancreatic cancer tumor dissemination is an event that can occur in early lesions, rather than being solely restricted in the developed primary tumor. Thus, the six hub genes that were differentially expressed between stage I and stage II of primary pancreatic cancer tumors were compared to metastasis-related genes (1938 genes) in the human cancer metastasis database (HCMDB), yielding two overlapped genes (B3GNT3 and FXYD3). To establish the expression correlation between these two specific genes with metastatic characteristics of the early stage of pancreatic cancer and migratory ability in pancreatic cancer cell lines, the expression patterns of B3GNT3 and FXYD3 were examined in four different migratory abilities of pancreatic cancer cell lines, including HPAC, BxPC-3, AsPC-1, and PANC-1, as well as the normal pancreatic duct epithelial cell line HPDE6-C7. The results displayed that the expression of the FXYD3 gene was dramatically increased with the migratory ability enhanced of four pancreatic cancer cell lines. Thus, in the follow-up study, we will demonstrate the functional role of FXYD3 in pancreatic cancer tumorigenesis. |
