食管癌是严重危害我国人民健康和生命的重大疾病。食管癌发生的一个最显著的特点是男性的发病率高于女性，因此性激素可能与食管癌的发生相关。研究表明雌激素能抑制食管癌的恶性增生，而雄激素的作用则相反，并且二者作用依赖于细胞核内雌激素受体（ER）和雄激素受体（AR）的表达。然而，性激素与食管癌发生的确切关系尚不清楚。本研究以ER、AR与食管癌发生发展关系为切入点，运用高通量技术（ChIP-exo、RNA-Seq）和生物信息学方法鉴定 ER 和 AR 调控的食管癌关键基因和通路；通过体内外实验明确ER 和 AR 对食管癌细胞增殖、凋亡、侵袭、迁移等生物学行为的影响；同时与临床紧密结合，在大样本食管癌组织中验证关键基因的表达与食管癌各临床指标的相关性，为食管癌的防治、个体化治疗乃至发掘新的治疗思路奠定基础。

Esophageal cancer is one of the major diseases that cause serious damage to the health of our people. The most significant characteristic of esophageal cancer is the higher incidence in men than women, so sex hormones are speculated to be among the causes of esophageal tumorigenesis. Previous studies have shown that estrogen inhibits esophageal malignant hyperplasia, while androgen stimulates such growth. These effects are the result of the expression and activity of estrogen receptor (ER) and androgen receptor (AR) in the epithelium of the esophagus. However, understanding of the functional roles of sex hormones in esophageal cancer is still in its infancy. The overall goal of this proposal is to investigate the functions of ER/AR in esophageal cancer. To accomplish this, we will use high-throughput sequencing approaches(ChIP-exo, RNA-Seq) and bioinformatics methods to define key ER/AR target genes and signaling pathways. We will also study the effect of ER/AR on the cell proliferation, apoptosis, invasion, migration and other relevant phenotypes of esophageal cancer in vivo and in vitro. We will finally assess the correlation between the expression of key ER/AR regulated genes and clinical pathologic parameters in a large collection of clinical esophageal cancer samples. Successful completion of this project will significantly advance our understanding of the molecular mechanisms of esophageal cancer tumorigenesis. This research will also lay a foundation for prevention, individualized treatment and new therapeutic strategies for esophageal cancer.