title: High coexpression of CCL2 and CX3CL1 is gender-specifically associated with good prognosis in soft tissue sarcoma patients.
abstract: 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.
authors.affiliation: Institute of Physiological Chemistry, Martin Luther University of Halle-Wittenberg, Halle, Germany.
authors.forename: Astrid
authors.initials: A
authors.lastname: Kehlen
authors.forename: Thomas
authors.initials: T
authors.lastname: Greither
authors.forename: Sven
authors.initials: S
authors.lastname: Wach
authors.forename: Elke
authors.initials: E
authors.lastname: Nolte
authors.forename: Matthias
authors.initials: M
authors.lastname: Kappler
authors.forename: Matthias
authors.initials: M
authors.lastname: Bache
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Holzhausen
authors.forename: Christine
authors.initials: C
authors.lastname: Lautenschläger
authors.forename: Steffen
authors.initials: S
authors.lastname: Göbel
authors.forename: Peter
authors.initials: P
authors.lastname: Würl
authors.forename: Uta-Dorothee
authors.initials: UD
authors.lastname: Immel
authors.forename: Abbas
authors.initials: A
authors.lastname: Agaimy
authors.forename: Bernd
authors.initials: B
authors.lastname: Wullich
authors.forename: Helge
authors.initials: H
authors.lastname: Taubert
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D049109:Cell Proliferation; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D054428:Chemokine CX3CL1 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012509:Sarcoma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D012737:Sex Factors; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C111835:CCL2 protein, human; C515538:CX3CL1 protein, human; D018932:Chemokine CCL2; D054428:Chemokine CX3CL1; D012333:RNA, Messenger
keywords: CCL2; CCL7; CX3CL1; chemokine; soft tissue sarcoma