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Abstract：
Endometrial cancer (UCEC) is one of three major malignant tumors in women. The HOX gene regulates tumor development. However, the potential roles of HOX in the expression mechanism of multiple cell types and in the development and progression of tumor microenvironment (TME) cell infiltration in UCEC remain unknown. In this study, we utilized both the The Cancer Genome Atlas (TCGA) database and International Cancer Genome Consortium (ICGC) database to analyze transcriptome data of 529 patients with UCEC based on 39 HOX genes, combing clinical information, we discovered HOX gene were a pivotal factor in the development and progression of UCEC and in the formation of TME diversity and complexity. Here, a new scoring system was developed to quantify individual HOX patterns in UCEC. Our study found that patients in the low HOX score group had abundant anti-tumor immune cell infiltration, good tumor differentiation, and better prognoses. In contrast, a high HOX score was associated with blockade of immune checkpoints, which enhances the response to immunotherapy. The Real-Time quantitative PCR (RT-qPCR) and Immunohistochemistry (IHC) exhibited a higher expression of the HOX gene in the tumor patients. We revealed that the significant upregulation of the HOX gene in the epithelial cells can activate signaling pathway associated with tumour invasion and metastasis through single-cell RNA sequencing (scRNA-seq), such as nucleotide metabolic proce and so on. Finally, a risk prognostic model established by the positive relationship between HOX scores and cancer-associated fibroblasts (CAFs) can predict the prognosis of individual patients by scRNA-seq and transcriptome data sets. In sum, HOX gene may serve as a potential biomarker for the diagnosis and prediction of UCEC and to develop more effective therapeutic strategies.
摘要：
子宫内膜癌(UCEC)是女性三大恶性肿瘤之一。HOX基因调节肿瘤的发展。然而,HOX在多种细胞类型的表达机制中以及在UCEC中肿瘤微环境（TME）细胞浸润的发展和进展中的潜在作用仍然未知。在这项研究中,我们利用癌症基因组图谱（TCGA）数据库和国际癌症基因组联盟（ICGC）数据库分析了基于39个HOX基因的529例UCEC患者的转录组数据，梳理临床信息，我们发现HOX基因是UCEC发生发展和TME多样性和复杂性形成的关键因素。这里,开发了一种新的评分系统来量化UCEC中的个体HOX模式.我们的研究发现,低HOX评分组患者有丰富的抗肿瘤免疫细胞浸润,良好的肿瘤分化，更好的预测。相比之下,高HOX评分与免疫检查点的封锁有关，增强了对免疫疗法的反应。实时定量PCR(RT-qPCR)和免疫组织化学(IHC)显示HOX基因在肿瘤患者中的较高表达。我们发现，上皮细胞中HOX基因的显著上调可以通过单细胞RNA测序（scRNA-seq）激活与肿瘤侵袭和转移相关的信号通路，如核苷酸代谢过程等。最后,通过HOX评分与癌症相关成纤维细胞(CAFs)之间的正相关关系建立的风险预后模型可以通过scRNA-seq和转录组数据集预测个体患者的预后.总之,HOX基因可作为诊断和预测UCEC的潜在生物标志物，并开发更有效的治疗策略。
