Plasma levels of M-CSF and VEGF in laboratory diagnostics and differentiation of selected histological types of cervical cancers

Abstract

Background The search of useful serum biomarkers for the early detection of cervical cancers has been of a high priority. The activation of Macrophage-Colony Stimulating Factor (M-CSF) and Vascular Endothelial Growth Factor (VEGF) is likely involved in the pathogenesis and spread of cancer. We compared the plasma levels of M-CSF and VEGF to the ones of commonly accepted tumor markers CA 125and SCC-Ag in three groups of patients: 1. the cervical cancer group (patients with either squamous cell carcinoma or adenocarcinoma); 2. the cervical dysplasia group; 3. the control group. Methods This cohort study included 100 patients with cervical cancer and 55 patients with cervical dysplasia. The control group consisted of 50 healthy volunteers. The plasma levels of VEGF and M-CSF were determined using ELISA, while CA 125 and SCC-Ag concentrations were obtained by the chemiluminescent microparticle immunoassay (CMIA). Results The median levels of M-CSF and VEGF as well as CA 125 and SCC-Ag in the entire group of cervical cancer patients, were significantly different compared to the healthy women group. In case of both the squamous cell carcinoma and the adenocarcinoma groups, plasma levels of M-CSF and VEGF were higher compared to the control group. No significant differences in the studied parameters between the squamous cell carcinoma and the adenocarcinoma group were observed. The highest sensitivity and specificity were obtained for VEGF (81.18 and 76.00%, respectively) and SCC-Ag (81.18%; 74.00%) in the squamous cell carcinoma group and for VEGF (86.67%; 76.00%) in the adenocarcinoma group. The area under the ROC curve for VEGF was the largest in the adenocarcinoma group followed by the squamous cell carcinoma group (0.9082 and 0.8566 respectively). Conclusions Obtained results indicate a possible clinical applicability and a high diagnostic power for the combination of MSC-F, VEGF, CA 125 and SCC-Ag in the diagnosis of both studied types of cervical cancer.

Novel biomarkers with promising benefits for diagnosis of cervical neoplasia: a systematic review

“…Macrophage colony-stimulating factor (M-CSF) is a hematopoietic growth factor that stimulates the proliferation and differentiation of Monocytes to macrophages. Experimental studies have shown that increased expression of M-CSF and its receptor leads to recruitment of tumor-associated macrophages (TAMs) in different types of cancers that also stimulate cancer cell proliferation and migration [5,47,48]. Consequently, M-CSF overexpression in plasma levels serves as useful predictor of carcinogenesis, and poor prognosis [46].…”

“…Finally, four of the studies evaluating Vascular Endothelial Growth Factor (VEGF) assays included in our review recorded sensitivity, specificity, and AUC ranges of 56-83.5%, 74.6-96%, and 0.83-0.86, respectively, [5,[50][51][52], with 86% PPV and 82% NPV reported by Ławicki, et al [50]. Our review findings supports earlier suggestion by Sidorkiewicz et aland Cheng et al, of the diagnostic usefulness, and clinical applicability of VEGF assay in cervical, breast or endometrial cancer, particularly with regards to consistency in specificity and AUC across all studies; and the diagnostic correlation with other complementary assays such as M-CSF and SCC-Ag [5,51]. Members of Vascular Endothelial Growth Factor (VEGF) family comprising VEGF-A, −B, −C, −D, and placenta growth factor (PlGF) are dimeric glycoprotein measuring 34-42 kDa, and constitutes one of the most important signaling pathways associated with angiogenesis [75].…”

“…3) For the p16INK4a / ki-67 assays, twenty studies included reported sensitivity, specificity, PPV, NPV, and AUC ranges of 50-100%, 39-90.4%, 11.1-92.3%, 86.7-100%, and 0.76-0.90, respectively, based on immunocytochemistry (ICC) platform using liquid based cytology (LBC) samples [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] . On the other hand, four studies evaluating Vascular Endothelial Growth Factor (VEGF) assay reported sensitivity, specificity, and AUC ranges of 56-83.5%, 74.6-96%, and 0.83-0.88, respectively, based on Elisa platform using serum [5,[50][51][52], with Lawicki et al being the only author who reported PPV and NPV at 86 and 82%, respectively. Overall, Table 1 is a summary of the performance characteristics for each of the 58 studies included.…”

“…Recent discoveries have demonstrated significant milestones in management of cervical cancer based on United States of America Food and Drug Administration (USFDA) approved biomarkers such as Squamous Cell Carcinoma Antigen (SCC-Ag) currently implemented to support physicians with rapid screening of women at high risk of cervical neoplasia, and complemented with Cancer Antigen 125 (CA-125), Serum Fragment of Cytokeratins (CYFRA), Soluble CD44 (sCD44), and Carcinoma Embryonic Antigen (CEA) as prognostic markers for pre-treatment prediction and disease monitoring [4]. Subsequently, new biomarkers such as Macrophage Colony Stimulating Factor (M-CSF), Vascular Endothelial Growth Factor (VEGF), MicroRNA, p16INKa / ki-67, HPV E6/E7/ mRNA and DNA methylation have equally been identified in the recent past as potentially useful for early detection of cervical neoplasia [5][6][7][8]. The aim of this systematic review was to describe the diagnostic performance of some selected biomarkers to detect highgrade cervical lesions (CIN2+) with histology as gold standard; and evaluated their implementation feasibility based on investigators findings, remarks and applicability as triage test for VIA or HPV positive women in low income settings.…”

Prediction of the treatment response in ovarian cancer: a ctDNA approach

“…Serum M-CSF appears to improve the diagnostic reliability of serum CA 125 alone [ 73 ]. • This biomarker expressed also in other cancers [ 74 ]. Bikunin Mediates suppression of tumor cell invasion and metastasis.…”