Upregulated Expression of C-X-C Chemokine Receptor 4 Is an Independent Prognostic Predictor for Patients with Gastric Cancer

Abstract

Aberrant chemokine (C-X-C motif) receptor CXCR4 expressions in malignant tissues have been reported, but its role in gastric cancer prognosis remains unknown. Our studies were designed to investigate the expression and prognostic significance of CXCR4 in patients with gastric cancer. CXCR4 expression was retrospectively analyzed by immunohistochemistry in 97 patients with gastric adenocarcinoma from China. Results were assessed for association with clinical features and overall survival by using Kaplan-Meier analysis. Prognostic values of CXCR4 expression and clinical outcomes were evaluated by Cox regression analysis. A molecular prognostic stratification scheme incorporating CXCR4 expression was determined by using receiver operating characteristic (ROC) analysis. The results show that CXCR4 predominantly localized in the cell membranes and cytoplasm. The protein level of CXCR4 was upregulation in gastric cancer tissues and upregulated expression of CXCR4 was only significantly associated with Lauren classification (P<0.001). Increased CXCR4 expression in gastric cancer tissues was positively correlated with poor overall survival of gastric cancer patients (P<0.001). Further multivariate Cox regression analysis suggested that intratumoral CXCR4 expression was an independent prognostic indicator for the disease. Applying the prognostic value of intratumoral CXCR4 density to TNM stage system showed a better prognostic value in patients with gastric cancer. In conclusion, intratumoral CXCR4 expression was recognized as an independent prognostic marker for the overall survival of patients with gastric cancer. On the basis of TNM stage, detection of CXCR4 expression will be helpful for predicting prognosis for patients with gastric cancer.

Inhibition of CXCL12/CXCR4 axis as a potential targeted therapy of advanced gastric carcinoma

“…CXCL12 expression is an independent prognostic factor for aggressive phenotypes of GC, including tumor size, invasion depth, lymphatic invasion and metastasis, TNM staging, surgical outcome, and the OS . The intensity of CXCR4 in primary GC lesion is positively associated with TNM staging, LN involvement, and recurrence/metastasis rate after radical surgery, but negatively with OS and disease‐free survival (DFS) . As for the combination of CXCR4 and CXCL12 levels, CXCR4 high /CXCL12 high in GC is significantly associated with tumor invasion depth, LN involvement, and higher TNM stage, which causes the worst prognosis, whereas patients with CXCR4 low /CXCL12 low show the best prognosis .…”

Infiltration of diametrically polarized macrophages predicts overall survival of patients with gastric cancer after surgical resection

“…The tissue microarray and immunohistochemistry protocols were constructed as described previously [25,26]. Primary antibodies were against CD68 (Dako, Glostrup, Denmark), CD11c (Abcam, Cambridge, MA, USA), and CD206 (Abcam, Cambridge, MA, USA).…”

Prognostic value of long noncoding RNA HOTAIR in digestive system malignancies

“…Despite recent advances in treatment, the prognosis of patients with cancers in digestive system remains poor. Numerous studies have reported molecular predictors of prognosis of patients with digestive system cancers . However, no specific molecular biomarker of this kind has been accepted commonly and used routinely until now.…”

“…Numerous studies have reported molecular predictors of prognosis of patients with digestive system cancers. [2][3][4][5] However, no specific molecular biomarker of this kind has been accepted commonly and used routinely until now. Clinically applicable biomarkers for prognosis analysis are urgently required.…”