肺腺癌的耐药和转移是临床治疗失败的主要原因。我们前期发现转录因子HOXB13与肺腺癌耐药、临床分级和预后生存相关。HOXB13在胚胎发育和肿瘤发生中起重要作用，但其与肺癌之间的关系尚无报道。本申请将结合临床病例检测及TCGA大数据库，明确HOXB13与肺腺癌化疗耐药、进展和预后之间的关系；通过体内、外功能实验明确HOXB13促进肺腺癌细胞耐药、转移及诱导肺癌干细胞亚群的功能；在全基因组范围内揭示HOXB13调控耐药和转移的下游靶基因，揭示HOXB13的相互作用蛋白，系统阐述HOXB13促进肺腺癌耐药与转移的分子机制。将结合肺腺癌病人穿刺活检，通过IHC和基因表达的定量检测，采用HOXB13及其靶基因组联合分析预测肺腺癌的耐药和预后。本研究首次提出了HOXB13与化疗耐药有关，并将探讨HOXB13及其靶基因联合应用的优越性及必要性，为肺腺癌的化疗耐药、转移倾向和预后评价提供新的判断方案。

Resistance to chemotherapy and metastasis of lung adenocarcinomas are the main causes of therapeutic failure in clinical patients. In our previous works we found that transcriptional factor HOXB13 is associated with drug resistance, clinical grading and prognosis of lung adenocarcinoma. HOXB13 plays an important role in embryonic development and tumorigenesis, but its role in lung cancer progression has not been reported. This grant proposal will identify the relationship between HOXB13 and lung adenocarcinoma progression, outcomes and resistance to chemotherapy by analyzing enlarged amount of clinical samples and also TCGA big datasets. We will clarify whether HOXB13 promotes drug resistance and metastasis of lung adenocarcinoma cells and induces the subpopulation of lung cancer stem cells through in vivo and in vitro functional experiments. Then we will systematically uncover the molecular mechanisms underlying HOXB13 regulation on drug resistance and metastasis in lung adenocarcinoma cells at the whole genome level by identifying the downstream target genes of HOXB13. Then we will identify the interacting proteins of HOXB13 in lung cancer cells. HOXB13 and the combination of its target genes will be examined for their usefulness in predicting the progression, drug resistance and prognosis of lung adenocarcinomas from biopsies of the patients. This study proposed for the first time that HOXB13 is associated with the resistance to chemotherapy. We seek to investigate the advantage and necessity of combined application of HOXB13 and its target genes to evaluate the therapeutic effects and prognosis for lung adenocarcinoma patients. This investigation anticipates to provide a new group of candidate genes for evaluation of drug resistance, metastasis and prognosis for lung adenocarcinoma patients.