Overexpression of macrophage-colony stimulating factor-1 receptor as a prognostic factor for survival in cancer

Abstract

Background: The relation between the expression of macrophage-colony stimulating factor-1 receptor (CSF-1R) and prognosis of cancer patients has been evaluated in multiple studies, but the results remain controversial. We, therefore, performed a meta-analysis and systematic review to figure out the role of CSF-1R in the prognosis of patients with cancer. Methods: Several databases were searched, including Web of Science, PubMed, and EMBASE. All human studies were published as full text. The Newcastle–Ottawa risk of bias scale was applied to evaluate the research. We extracted hazard ratios (HRs) with 95% confidence interval (95% CI) which assessed progression-free survival (PFS) and overall survival (OS) in order to assess the impacts of CSF-1R on the prognosis of cancer patients. Results: A total of 12 citations were identified, with studies including 2260 patients in different cancer types that met the eligibility criteria. It was suggested in a pooled analysis that the over-expression of CSF-1R was significantly related to worse PFS (HR: 1.68; P < .001, 1.25–2.10, 95% CI) and also poorer OS (HR=1.28; P < .001, 1.03–1.54, 95% CI). Analysis in subgroups indicated over-expressed CSF-1R was significantly associated with worse OS in hematological malignancy (HR = 2.29; P < .001, 1.49–3.09, 95% CI; model of fixed-effects; I 2 = 0.0%, P < .001). Sensitivity analysis suggested that there was no study influencing the stability of the results. Conclusions: The overexpression of CSF-1R was significantly predictive of worse prognosis in those who suffer from different kinds of malignancies, particularly in hematological malignancy, which indicates that it might be a potential biomarker of prognosis in cancer survival and a potential molecular target in the treatment of malignant tumors.

Vav1 Promotes B-Cell Lymphoma Development

“…Under physiological conditions, CSF-1 is produced by fibroblasts, endothelial cells, monocytes, macrophages, osteoblasts, microglia, keratinocytes, bone marrow stromal cells, natural killer cells, B-cells and T-cells and epithelial cells [65,66]. It is an essential regulator of development and homeostasis of the mononuclear phagocyte system and, by extension, a key factor of CSF1-dependent macrophage control of development and homeostasis [64,67,68]. CSF-1 appears to play an autocrine and/or paracrine role in cancers of the ovary, endometrium, breast, lung, the nervous system, and myeloid and lymphoid tissues, within which overexpression of CSF-1 receptor is considered as a prognostic factor for survival in cancer [68].…”

“…It is an essential regulator of development and homeostasis of the mononuclear phagocyte system and, by extension, a key factor of CSF1-dependent macrophage control of development and homeostasis [64,67,68]. CSF-1 appears to play an autocrine and/or paracrine role in cancers of the ovary, endometrium, breast, lung, the nervous system, and myeloid and lymphoid tissues, within which overexpression of CSF-1 receptor is considered as a prognostic factor for survival in cancer [68].…”

Colony-stimulating factor-1 receptor inhibition combined with paclitaxel exerts effective antitumor effects in the treatment of ovarian cancer

“…Meanwhile, the autophosphorylation of the CSF-1R signaling pathway is effectively inhibited by PLX3397, resulting in the inhibition of the downstream signaling molecules PI3K, AKT, ERK, and RAF, which affect tumor cell function. 18 , 19 In vivo studies found that pexidartinib/PTX treatment led to a remarkable reduction in CD31 + vascular density within mammary tumors and induced apoptosis and necrosis of tumor cells in the MMTV-PyMT mouse model of breast cancer. 7 To date, preclinical studies on the antitumor effects of PLX3397 have been conducted in hepatocellular carcinoma, cervical cancer, and melanoma.…”

Potential Stereoselective Binding of Trans-(±)-Kusunokinin and Cis-(±)-Kusunokinin Isomers to CSF1R

“…CSF1R is responsible for cancer cell proliferation, invasion and survival [15][16][17][18][19][20][21]. CSF1R is strongly related to poor outcomes and contributes to tumor cell invasiveness and pro-metastatic behavior [12,15,18,[22][23][24][25][26]. Pexidartinib, a pyrrolopyridine-based compound, is the first FDA-approved CSF1R tyrosine kinase inhibitor [27,28].…”