I型干扰素广泛应用于治疗恶性肿瘤，但在肝癌患者中有较大疗效差异，寻求IFN-α疗效预判的分子靶标、探求IFN-α疗效的影响因素并进行相应干预以提高患者对IFN-α治疗的反应性成为亟待解决的重要问题。IFN-a的生物学效应依赖干扰素诱导基因(ISG)的表达，申请人所在课题组通过系统筛选ISG在肝癌中的差异表达，发现RIG-I和IFIT家族分子在肝癌组织中表达均有显著降低，且已证实RIG-I能够促进IFN对肝癌的疗效并作为肝癌IFN治疗疗效预测的分子靶标(Cancer Cell 2014)。IFIT家族分子的作用则有待确定。本研究拟以肝癌为模型，系统研究IFIT家族分子是否通过影响IFN下游效应信号通路影响其他ISG产生，从而对I型干扰素的抗肝癌作用产生影响，并研究IFIT家族分子表达水平是否影响IFNα治疗敏感性，以期提出新的IFN治疗疗效预判的分子靶标，为提高IFNα疗效提供新思路。

Interferon, especially IFN-α, is widely used in the treatment of malignancies, but for hepatocellular carcinoma patients, it have showed diverse curative outcomes among different patients. Thus, it is clearly urgent to search potential biomarkers for predicting the response to IFN-α adjuvant therapy and to identify the well-responders. Moreover, it is also essential to clarify the underlying molecular mechanisms influencing the response to IFN-α therapy and to open new avenues to improve it. The biological functions of IFN-α rely on the functions of interferon-stimulated genes (ISGs). And our group had applied cDNA microarray and focused on differentially expressed ISGs in HCC tissues, and compared to those in matched nontumor liver tissues, through which we identified RIG-I as a potential candidate. In the following studies, we have demonstrated that RIG-I could enhance response to IFN-α therapy in HCC and the RIG-I expression in HCC tissues may be useful as an independent predictor for IFN-α treatment response. This works has already been published as the cover story of Cancer Cell, with an impact factor of 25.6. Besides RIG-I, we also noticed IFIT family members, including IFIT1\2\3\5 were dramatically downregulated in HCC tissues, and despite the antiviral effects of IFIT family members, its antitumor effect or its effect on IFN pathway are still largely unknown. Thus, we will use hepatocellular carcinoma as a model and focus on the effects and mechnisms of IFITs in the IFN pathway, hoping to identify whether IFITs could also predict the curative outcomes of IFN-therapy as well as providing clues to improve the treatment.