Zhang Jianbo, Liu Chengxin, Mo Xinkai, Shi Huan, Li Sheng
Department of Pathology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong 250117, P.R. China.
Department of Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong 250117, P.R. China.
Oncol Lett. 2018 Feb;15(2):1771-1776. doi: 10.3892/ol.2017.7512. Epub 2017 Dec 5.
C-X-C motif chemokine receptor (CXCR) 4/CXCL12 is associated with tumor invasion and metastasis in pancreatic cancer. The present study aimed to investigate the possible mechanisms behind this process by studying the association between the expression of CXCR4 and numerous molecular markers. A total of 60 patients with pancreatic cancer who had been treated with radical surgery between July 2012 and February 2016 were included in the present study. The expression of CXCR4/CXCL12 in primary pancreatic cancer lesions, tissues adjacent to cancerous tissue, non-cancerous pancreatic tissues and in the surrounding lymph nodes was evaluated by immunohistochemistry. Expression levels of four candidate biomarkers [vascular endothelial growth factor-C (VEGF-C), Ki-67, matrix metalloproteinase 2 (MMP-2) and β-catenin] were also evaluated. The correlation between CXCR4 and these four biomarkers was assessed. CXCR4 (CXCL12) expression levels were higher in pancreatic cancer 56.7% (86.7%), paracancerous tissue 50.0% (85.0%) and surrounding lymph nodes 53.3% (80.0%), compared with in normal tissues 18.3% (45.0%). CXCR4 expression was significantly associated with the lymph node metastasis of tumors (P=0.001), pathological type (P=0.037) and tumor-node-metastasis stage (P=0.031). CXCR4 expression exhibited a positive correlation with VEGF-C (r=0.417; P=0.001), Ki-67 (r=0.316; P=0.014), MMP-2 (r=0.284; P=0.028) and β-catenin (r=0.368; P=0.04). Furthermore, logistic regression analysis revealed VEGF-C (β=1.722; P=0.005) and Ki-67 (β=1.196; P=0.047) to be two biomarkers that cause metastasis via CXCR4. CXCR4/CXCL12 is closely associated with tumor grade and lymphatic metastasis. VEGF-C and Ki-67 are two important biomarkers, through which CXCR4 initiates metastatic behavior in pancreatic cancer. Therefore, angiogenesis inhibitors will continue to be effective agents in treating pancreatic cancer.
C-X-C基序趋化因子受体（CXCR）4/CXCL12与胰腺癌的肿瘤侵袭和转移相关。本研究旨在通过研究CXCR4表达与多种分子标志物之间的关联，探讨这一过程背后的可能机制。本研究纳入了2012年7月至2016年2月间接受根治性手术治疗的60例胰腺癌患者。采用免疫组织化学法评估CXCR4/CXCL12在原发性胰腺癌病灶、癌旁组织、非癌胰腺组织及周围淋巴结中的表达。还评估了四种候选生物标志物[血管内皮生长因子-C（VEGF-C）、Ki-67、基质金属蛋白酶2（MMP-2）和β-连环蛋白]的表达水平。评估了CXCR4与这四种生物标志物之间的相关性。与正常组织18.3%（45.0%）相比，CXCR4（CXCL12）在胰腺癌中的表达水平为56.7%（86.7%），癌旁组织为50.0%（85.0%），周围淋巴结为53.3%（80.0%）。CXCR4表达与肿瘤的淋巴结转移（P=0.001）、病理类型（P=0.037）和肿瘤-淋巴结-转移分期（P=0.031）显著相关。CXCR4表达与VEGF-C（r=0.417；P=0.001）、Ki-67（r=0.316；P=0.014）、MMP-2（r=0.284；P=0.028）和β-连环蛋白（r=0.368；P=0.04）呈正相关。此外，逻辑回归分析显示VEGF-C（β=1.722；P=0.005）和Ki-67（β=1.196；P=0.047）是通过CXCR4导致转移的两种生物标志物。CXCR4/CXCL12与肿瘤分级和淋巴转移密切相关。VEGF-C和Ki-67是两种重要的生物标志物，CXCR4通过它们引发胰腺癌的转移行为。因此，血管生成抑制剂将继续是治疗胰腺癌的有效药物。
