High expression of CRAM correlates with poor prognosis in patients with cervical carcinoma.
OBJECTIVE
Atypical chemokine receptors (ACRs) have been reported to scavenge or alter the localization of their chemokine ligands. However, CRAM, a newly identified ACR member, is lack of ligand scavenging properties. The present study was to investigate the clinical significance of CRAM in cervical carcinoma.


METHODS
The expression of CRAM in primary cervical cancer and paired normal tissues from adjacent regions was examined using Real time PCR. Moreover, CRAM protein expression was analyzed in 272 cervical specimens including 50 normal cervical tissues, 40 cases of carcinoma in situ of cervix (CIS), and 182 cases of cervical cancer by immunohistochemistry.


RESULTS
Real time PCR showed that the expression level of CRAM was markedly higher in cervical cancer than that in normal cervical tissues. The expression rate of CRAM in normal cervical tissues, CIS, and cervical cancer increased gradually (p < 0.01). In addition, the expression level of CCL19 was positively associated with that of CRAM (p < 0.05). Moreover, high expression level of CRAM was correlated with lymph node metastasis and histological subtype. In multivariate Cox regression analysis, high expression level of CRAM was a negative indicator for both overall (p = 0.028) and recurrence-free survival (p = 0.010).


CONCLUSIONS
The present study suggested that CRAM could be a clinical prognostic marker for patients with cervical cancer and might be a potential therapeutic target for cervical cancer. Our data extended previous research on the predictive value of ACRs.
State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine Guangzhou, GD 510060, China.
Teng
T
Hou
Department of Gynecology, Henan Cancer Hospital, The Affiliated Cancer Hospital of Zhengzhou University Zhengzhou, HN 450008, China.
Dongxia
D
Liang
Department of Urology, Henan Cancer Hospital, The Affiliated Cancer Hospital of Zhengzhou University Zhengzhou, HN 450008, China.
Dong
D
Yang
State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine Guangzhou, GD 510060, China.
Jiehua
J
He
State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine Guangzhou, GD 510060, China.
Yongwen
Y
Huang
State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine Guangzhou, GD 510060, China.
Yanna
Y
Zhang
D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D006867:Hydrolases; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008869:Microtubule-Associated Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D011379:Prognosis; D016016:Proportional Hazards Models; D060888:Real-Time Polymerase Chain Reaction; D019707:Receptors, Chemokine / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D002578:Uterine Cervical Dysplasia / Q000378:metabolism / Q000401:mortality / Q000473:pathology*
D014408:Biomarkers, Tumor; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D019707:Receptors, Chemokine; C415087:DPYSL5 protein, human; D006867:Hydrolases
Atypical chemokine receptor; CRAM; cervical cancer; prognosis