Integrated analysis of tumor-associated macrophage infiltration and prognosis in ovarian cancer

• Published in: Aging (Albany, NY.) NY.), 2021-10, Vol.13 (19), p.23210-23232
• Main Authors: Tan, Qianxia, Liu, Huining, Xu, Jie, Mo, Yanqun, Dai, Furong
• Format: Article
• Language: English
• Subjects: Biomarkers, Tumor - genetics; Biomarkers, Tumor - immunology; Biomarkers, Tumor - metabolism; Female; Humans; Ovarian Neoplasms - diagnosis; Ovarian Neoplasms - genetics; Ovarian Neoplasms - mortality; Ovarian Neoplasms - pathology; Prognosis; Research Paper; Tumor-Associated Macrophages - immunology
• ISSN: 1945-4589; 1945-4589
• DOI: 10.18632/aging.203613

Ovarian cancer (OC) is a frequently lethal gynecologic malignancy, characterized by a poor prognosis and high recurrence rate. The immune microenvironment has been implicated in the progression of OC. We characterized the immune landscape in primary and malignant OC ascites using single-cell and bulk transcriptome raw OC data acquired from the Gene Expression Omnibus and The Cancer Genome Atlas databases. We then used the CIBERSORT deconvolution algorithm, weighted gene co-expression network analysis, univariate and multivariate Cox analyses, and the LASSO algorithm to develop a tumor-associated macrophage-related gene (TAMRG) prognostic signature, which enabled us to stratify and predict overall survival (OS) of OC patients. In addition, inter- and intra-patient heterogeneity of infiltrating immune cells was characterized at single-cell resolution. Tumor-infiltrating macrophages with an M2 phenotype exhibited immunosuppressive activity. M1 macrophages positively correlated with OS, whereas activated mast cells, neutrophils, M2 macrophages, and activated memory CD4 T cells were all negatively correlated with OS. A total of 219 TAMRGs were identified, and a novel 6-gene signature ( , , , , , and ) with independent prognostic value was established. These results show that a TAMRG-based signature may be a promising prognostic and therapeutic target in OC.