原发性肝细胞癌具有易复发转移的特点，病死率居高不下。肺转移为肝癌远处侵袭转移最常见的类型，最新研究发现肝癌细胞可与肺源性细胞相互作用，促进转移前微环境的形成，利于肿瘤细胞的定植。几丁质酶-3样蛋白-1（YKL-40）是肺部慢性炎症微环境中重要的细胞因子，在哮喘等多种肺部疾病中显著上调，且与多种肿瘤及慢性肝炎患者预后呈负相关。本课题组长期从事肝癌复发转移机制研究，前期预实验发现肝细胞癌肺转移患者血清中YKL-40水平特异性升高；细胞模型发现肝癌细胞可诱导肺上皮细胞分泌YKL-40，分泌水平与肝癌细胞的侵袭性相关。因此，我们提出YKL-40可能介导肝癌细胞肺转移的科学假设。本课题拟评估YKL-40作为肝细胞癌肺转移血清学标志物的潜在价值，并探讨肺源性细胞分泌YKL-40诱导肝癌肺转移的机制。本课题研究为阐释肝癌肺转移的机制提供理论基础，为研发新的干预策略提供新思路。

Primary hepatocellular carcinoma (HCC) is a disease with high mortality, which is characterized with the inclination to recurrence and metastasis. Lung metastasis is the most frequent distant invasion progression. The primary tumor has been supposed to be able to educate the secondary sites by promoting the formation of supportive metastatic environment, termed the pre-metastatic niche. Chitinase-3-like-1 is a secreted protein that is upregulated in various types of lung chronic inflammation diseases, such as bronchial asthma, correlated with the severity of these diseases. Moreover, a number of studies have demonstrated strong correlations between YKL-40 expression and the development of primary and metastatic tumors, as well as chronic inflammatory liver diseases. Therefore, we focused on the role of YKL-40 on lung metastasis of primary hepatocellular carcinoma and its mechanism. In our preliminary study, we have detected significantly higher level of serum YKL-40 in liver cancer patients with lung metastasis. Also, HCC cell line could promote the secretion of YKL-40 in lung epithelial cells in a manner dependent on the invasiveness of tumor cells. Based on the above evidence, this project aims to elucidate the mechanism underlying the secretion of YKL-40 by lung epithelial cells and its role in lung metastasis of HCC. Moreover, this project would also explore the possibility of YKL-40 as a serum biomarker to predict lung metastasis of HCC, which might be of potential value in personalized medicine.