The Diagnostic Significance of PDGF, EphA7, CCR5, and CCL5 Levels in Colorectal Cancer

Abstract

In this study, we compared the levels of C-C chemokine receptor type 5 (CCR5), C-C motif chemokine ligand 5 (CCL5), platelet-derived growth factor (PDGF), and EphrinA7 (EphA7) in patients with colorectal carcinoma and healthy controls in order to investigate the significance and usability of these potential biomarkers in early diagnosis of colorectal cancer. The study included 70 colorectal carcinoma patients and 40 healthy individuals. The CCR5, CCL5, PDGF, and EphA7 levels were measured using ELISA in blood samples. PDGF-BB, EphA7, CCR5, and CCL5 levels of the patients with colorectal carcinoma were significantly higher compared to the control group (p < 0.001 for each comparison). Our logistic regression analysis (the area under the curve was 0.958) supports the notion that PDGF-BB, EphA7, and CCL5 are potential biomarkers for the diagnosis of colon cancer. The sensitivity, specificity, and positive and negative predictive values were found to be 87.9%, 87.5%, 92.1%, and 81.4%, respectively. To our knowledge, this is the first study that investigates the relationship between colorectal carcinoma and the four biomarkers CCL5, CCR5, PDGF, and EphA7. The significantly elevated levels of all these parameters in the patient group compared to the healthy controls indicate that they can be used for the early diagnosis of colorectal carcinoma.

Biphasic Temporal Relationship between Cancers and Systemic Sclerosis: A Clinical Series from Montpellier University Hospital and Review of the Literature

“…The occurrence of cancer 10 years after SSc diagnosis is compatible with a reasonable mean length of time for the effect of chronic inflammation or immunosuppressive drugs on carcinogenesis. Cytokine dysregulation may also play a role in both diseases: apart from angiogenesis factors, for example platelet-derived growth factor (PDGF) would appear to be involved in both carcinogenesis and lung fibrosis [43][44][45]. Lastly, abnormalities in mesenchymal cell homeostasis (fibroblast cells, endothelial cells), leading to both fibrosis and carcinogenesis, may also be involved in both carcinogenic and dysimmune processes [1].…”

The “Janus Face” of Platelets in Cancer

“…Such evidence, together with the finding that tumor-derived IL-6 leads to enhanced megakaryocyte VEGF expression and a higher platelet VEGF load (concomitantly associated with fast tumor growth kinetics and poor diagnosis), strongly suggest a cooperation between platelets and cancer in promoting angiogenesis [121]. Conversely, low EGF levels have been found in cancer subjects with recurrence, and an inverse correlation between its concentrations and survival [118] has been documented in these subjects. Low serum Ang-1 levels, related to poor diagnosis, were also found in subjects with certain types of cancer [118].…”

“…In the latter case, a protective role of PDGF-BB has been suggested, since its overexpression, by increasing tumor pericyte content, decreases colorectal and pancreatic cancer growth [116]. However, data on PDGF-BB content in cancer patients are controversial: Concentrations of secreted PDGF-BB, for example, have been found to be significantly high in the serum of colorectal carcinoma patients [117], but low in liver cancer patients with recurrence [118].…”

“…Conversely, low EGF levels have been found in cancer subjects with recurrence, and an inverse correlation between its concentrations and survival [118] has been documented in these subjects. Low serum Ang-1 levels, related to poor diagnosis, were also found in subjects with certain types of cancer [118]. On the contrary, patients with lung and ovarian cancer show high Ang-1 concentrations not related to patient survival [122].…”

“…Such different behavior is much likely due to the ability of serotonin to act in a concentration-dependent manner, as well as in its capability to activate distinct signaling pathways, depending on the receptor subtype present at various tumor stages. Coherently, high serotonin levels, correlating with the tumor stage, distant metastases and a poor prognosis, have been found in the serum of patients with different solid tumors [131,[135][136][137], whereas low concentrations have been found in hepatocellular carcinoma patients, who showed recurrence after partial hepatectomy [118]; in untreated breast adenocarcinoma or malignant melanoma patients, where the phenotype (also associated with a high ATP/ADP ratio and index of delta storage pool deficiency) was more marked in regionally spread malignant tumors [138].…”