全球每年約有75萬人被診斷為肝癌且占全球癌症死亡率排列第三位，肝癌的危險因子主要有病毒感染、過量酒精攝取、基因、暴露於致癌物質及環境化學物質等，然而肝癌治療上常常會遇到抗藥性的產生或預後率偏低的情形，因此開發新治療策略是急迫切需的。在過去我們的實驗發現內質網壓力可以誘導肝癌細胞株過量表現Nucleobindin-2 (NUCB-2)，然而NUCB-2在臨床檢體的表現情形仍未清楚，因此本實驗目的將分析肝癌檢體中內質網壓力及NUCB-2表現情形。檢體來源主要分成30組非B和C型肝炎的肝癌組織(NBNC HCC)、45組B型肝炎病毒肝癌組織(HBV HCC)及45組C型肝炎病毒肝癌組織(HCV HCC)，我們利用real-time PCR分析120組人體臨床肝癌檢體的GRP78 (ER stress marker)與NUCB-2的表現情形，結果顯示在120組肝癌發現感染B和C肝炎病毒的肝癌組織中有NUCB-2過量表現情形，進一步分析發現內質網壓力標記基因GRP78基因表現與NUCB-2基因表現呈現正相關性。同時進一步分析NUCB-2表現與性別、腫瘤階段、腫瘤大小、腫瘤侵襲、肝硬化及存活率之間的關係。接著我們分析NUCB-2 shRNA在內質網壓力過程中NUCB-2對MAPK通路的影響，結果發現Huh-7 NUCB-2 shRNA細胞在p38磷酸化中有增加的情形。因此，這研究機制可能為NUCB-2高表現癌症患者在分子機礎提供一個全新的生物標記。 Liver cancer the approximately 750,000 new cases per year currently representing the third leading cause of cancer-related deaths worldwide.The most common risk factors associated with HCC are virus infection, alcohol, gene mutation, carcinogens and environmental chemicals exposure. HCC is one of the most common malignancies worldwide with poor prognosis due to resistance to conventional chemotherapy and limited efficacy of radiotherapy. Therefore, the development of new therapeutic targets for liver cancer is urgently needed. Our previous have indicated that expression of nucleobindin-2 (NUCB-2) was increased by endoplasmic reticulum stress (ER stress). However, the expression status of NUCB-2 in HCC samples is still unclear. Therefore, the aim of this experiment is to analyze the expression of ER stress and NUCB-2 expression in HCC samples. 120 HCC samples were divided into 30 groups of non-B and C hepatocellular carcinoma tissues, 45 groups of hepatitis B virus hepatocellular carcinoma (HBV-HCC) and 45 groups of hepatitis C virus (HCV-HCC). The expression levels of GRP78(ER stress marker) and NUCB-2 was determined by using real-time PCR. The results showed that overexpression of GRP78 and NUCB-2 was observer in HBV-HCC and HCB-HCC samples. Furthermore, expression level of NUCB-2 was positively correlated with GRP78 expression. In addition, the relationship between NUCB-2 expression and gender, tumor stage, tumor size, tumor invasion, liver cirrhosis and survival rate. The effect of NUCB-2 on MAPK pathways during ER stress was performed by NUCB-2 shRNA, and phosphoryaltion of p38 was increased in Huh-7 NUCB-2 shRNA cells. Consequently, this mechanistic research may provide a molecular basis to develop a biomarker and novel cancer chemotherapeutic agent for high level expression of NUCB-2 in cancer patients.
