Effects of HOX family regulator-mediated modification patterns and tumor immunity characteristics on cancer- associated fibroblasts in endometrial cancer

Endometrial cancer is one of three major malignant tumors in women. The HOX gene regulates tumor development. However, the potential roles of HOX in the development and progression of endometrial cancer, cancer-associated fibroblasts (CAFs), and tumor microenvironment (TME) cell infiltration remain unknown. Here, a new scoring system was developed to quantify individual HOX patterns in uterine corpus endometrial cancer (UCEC). Meanwhile, our research was verified by immunohistochemistry and real-time quantitative PCR (RT-qPCR) and Single-cell RNA sequencing (scRNA-seq). Our study found that patients in the low HOX score group had abundant anti-tumor immune cell infiltration, good tumor differentiation, and better prognoses. Meanwhile, a high HOX score was associated with blockade of immune checkpoints, which enhances the response to immunotherapy. HOX gene was a pivotal factor in the development and progression of endometrial cancer and in the formation of tumor microenvironment diversity and complexity. HOX genes are involved in the regulation of CAF formation, and thus change microenvironments to promote tumor growth, invasion, and metastasis. In sum, HOX scores can be used as a new biomarker for the diagnosis and prediction of UCEC and to develop more effective therapeutic strategies.