Abstract
Endometrial cancer (EC) is one of the most common gynecologic malignancies. To identify potential prognostic biomarkers for EC, we analyzed the relationship between the EC tumor microenvironment and gene expression profiles. Using the ESTIMATE R tool, we found that immune and stromal scores correlated with clinical data and the prognosis of EC patients. Based on the immune and stromal scores, 387 intersection differentially expressed genes were identified. Eight immune-related genes were then identified using two machine learning algorithms. Functional enrichment analysis revealed that these genes were mainly associated with T cell activation and response. Kaplan-Meier survival analysis showed that expression of TMEM150B, CACNA2D2, TRPM5, NOL4, CTSW, and SIGLEC1 significantly correlated with overall survival times of EC patients. In addition, using the TIMER algorithm, we found that expression of TMEM150B, SIGLEC1, and CTSW correlated positively with the tumor infiltration levels of B cells, CD8+ T cells, CD4+ T cells, macrophages, and dendritic cells. These findings indicate that the composition of the tumor microenvironment affects the clinical outcomes of EC patients, and suggests that it may provide a basis for development of novel prognostic biomarkers and immunotherapies for EC patients.
Highlights
IntroductionEndometrial cancer (EC) is one of the most common gynecologic malignancies, and the fourth most common cancer (about 4.8% of all cancers) in women [1]
Endometrial cancer (EC) is one of the most common gynecologic malignancies, and the fourth most common cancer in women [1]
Based on the clinical data extracted from The Cancer Genome Atlas (TCGA)-CDR (Supplementary Table 2) and using Wilcoxon signedrank test, we found that both immune and stromal scores of grade 3 (G3; n=319) and high-grade (n=11) EC were significantly lower compared to grade 1 (G1; n=96) and grade 2 (G2; n=119) groups (p=0.03, p=0.04)
Summary
Endometrial cancer (EC) is one of the most common gynecologic malignancies, and the fourth most common cancer (about 4.8% of all cancers) in women [1]. EC affects mainly post-menopausal women [2]. The routine treatment for EC includes surgery, radiotherapy, chemotherapy, and hormonal therapy. When the disease is confined to the uterus, EC patients have a relatively good prognosis, with a 5-year survival rate of 95 %. When distant metastases are present at the time of diagnosis, the 5-year survival rate is only 17 %, and patients respond poorly to conventional therapies. It is critical to identify prognostic biomarkers for EC, and develop therapies that are more effective for patients with advanced forms of EC
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