High coexpression of CCL2 and CX3CL1 is gender‐specifically associated with good prognosis in soft tissue sarcoma patients

• Published in: International journal of cancer 2014-11, Vol.135 (9), p.2096-2106
• Main Authors: Kehlen, Astrid, Greither, Thomas, Wach, Sven, Nolte, Elke, Kappler, Matthias, Bache, Matthias, Holzhausen, Hans‐Jürgen, Lautenschläger, Christine, Göbel, Steffen, Würl, Peter, Immel, Uta‐Dorothee, Agaimy, Abbas, Wullich, Bernd, Taubert, Helge
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Apoptosis; Biological and medical sciences; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Blotting, Western; Cancer; CCL2; CCL7; Cell Proliferation; chemokine; Chemokine CCL2 - genetics; Chemokine CCL2 - metabolism; Chemokine CX3CL1 - genetics; Chemokine CX3CL1 - metabolism; Chemokines; CX3CL1; Dermatology; Female; Follow-Up Studies; Gender; Humans; Immunoenzyme Techniques; Male; Medical prognosis; Medical research; Medical sciences; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Multivariate analysis; Neoplasm Grading; Neoplasm Staging; Prognosis; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Sarcoma - genetics; Sarcoma - metabolism; Sarcoma - mortality; Sex Factors; soft tissue sarcoma; Survival Rate; Tumor Cells, Cultured; Tumors; Tumors of the skin and soft tissue. Premalignant lesions; Young Adult
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.28867

Chemokines are involved in both the negative and positive regulation of inflammatory processes, angiogenesis and cancer/cancer stem cell proliferation as well as the chemoattraction of tumor cells to metastatic sites. The aim of this study was to measure the mRNA expression levels of three chemokines, CCL2, CCL7 and CX3CL1, in soft tissue sarcomas (STSs) and to assess the correlations between these levels as well as their correlations with clinicopathological data and the disease‐specific survival of STS patients. The mRNA levels of CCL2, CCL7 and CX3CL1 were analyzed in tumor tissues from 126 STS patients using qPCR. Low mRNA expression of CCL2 and CX3CL1 was significantly correlated with a worse prognosis (RR = 1.98; p = 0.019 and RR = 2.10; p = 0.014; multivariate Cox's regression analysis). A combined low expression of CCL2 and CX3CL1 was associated with a significantly increased risk of tumor‐related death as compared to patients with high expression levels of both chemokines (RR = 3.08; p = 0.003). A gender‐specific multivariate analysis revealed that female STS patients with low CX3CL1 mRNA expression had a 3.46‐fold increased risk of death (p = 0.004). Low expression of both CCL2 and CX3CL1 mRNAs resulted in an additive 5.37‐fold increased risk of tumor‐related death (p = 0.003) as compared to those with high expression of both parameters in female patients. In conclusion, this is the first study to show a significant correlation between combined low expression of CCL2 and CX3CL1 and a poor prognosis for STS patients, particularly in female patients. What's New? While chemokines are known to play key roles in both driving and preventing cancer progression, their expression and biological significance in soft tissue sarcoma (STS) remain unclear. This study shows that monocyte chemotactic protein‐1 (MCP1/CCL2) and fractalkine (CX3CL1) affect the prognosis of STS patients. The high mRNA expression of both chemokines is correlated with a good outcome in STS patients, particularly in female STS patients. The study provides evidence supporting the hypothesis that CCL2 and CX3CL1 have a promoting effect on apoptosis induction in STS. A possible explanation for the gender difference is the gender‐specific regulation of chemokines by hormones/receptors.