A Study On The Expression Of Chemokine CXCL12/CXCR4in Non-small Cell Lung Cancer

Objective:Lung cancer is the most commonly diagnosed malignancy and the leading cause of cancer-related deaths worldwide. Because metastatic spread constitutes the primary source of morbidity and mortality,a thorough understanding of the metastatic process is likely to be crucial to developing effective new therapies for lung cancer. Recently, a growing appreciation of the role chemokines in cancer has unlocked the secrets of some of the molecular pathways underpinning this process,creating an understanding that reflects Paget’s "seed and soil hypothesis"and which may lead to new approaches to lung cancer management. Recent studies indicate that tumor cells express chemokine receptors and may use chemokine-mediated mechanisms during the metastasis process.The expression of CXCL12/CXCR4in NSCLC patients was detected by immunohistochemistry and RT-PCR in our study. Our aim is to investigate the correlation between the expression of the two factors and clinical parameters in NSCLC and study their roles in invasion and metastasis of NSCLC.Methods:95cases paraffin-embeded NSCLC samples were analyzed and27benign tumors were also studied as controls.All subjects were taken from the patients who admitted for operative treatment in the Tianjin Chest Hospital from2006.10to2008.10.The expression of CXCL12and CXCR4protein was detected by immunohistochemical staining.We observed their expression to explore the influence on tumor metastasis, their mutual relationship, the relationship with the clinicopathologic parameters.CXCL12mRNA and CXCR4mRNA on frozen lung tumor samples were detected by RT-PCR to analyze their expression with tumor metastasis and the relationship with clinicopathologic parameters. Those tissues were taken from the patients who admitted for operative treatment in the Tianjin Chest Hospital from2010.9to2011.9. Data were performed with13.0software. Chi-square test, Student t test and Pearson rank correlation were used. Data were considered statistically significant if p values were0.05or less.Results:1. Immunohistochemistry results:(1)The expression of CXCL12and CXCR4protein has no relationship to patients’age, gender, tumor size, tissue typing, and clinical classification(P>0.05).The expression of CXCL12and CXCR4in metastatic group is higher than non-metastatic group(P<0.05). The expression rate of CXCL12and CXCR4is increasing with TNM stage, and stage Ⅲ is higher than stage Ⅰ (P<0.05). The expression rate of CXCL12and CXCR4in control group is significantly lower than in NSCLC group(P<0.05).(2)Pearson rank correlation analysis showed that the expression of CXCL12had no correlation with the expression of CXCR4(r=0.173, P>0.05).2. RT-PCR results:(1)The expression of CXCL12and CXCR4mRNA in NSCLC group is much higher than in control group, in metastatic group is higher than in non-metastatic group. The expression of the two genes is increasing with TNM stage, and stage Ⅲ is higher than stage Ⅰ.(2)Liner correlation analysis showed that the expression of CXCL12had correlation with the expression of CXCR4in NSCLC group (P<0.05).Conclusions:1. The expression of CXCL12and CXCR4is not related to patients’age, gender, tissue typing, tumor size, and clinical classification. The expression of CXCL12and CXCR4is much higher than in control group, in metastatic group is much higher than in non-metastatic group, and is related to TNM stage. It is found that CXCL12mRNA is related to CXCR4mRNA in NSCLC group in RT-PCR test, and CXCL12protein is not related to CXCR4protein in immunohistochemical staining. We need to investigate whether there is relationship between primary lesions and metastatic lesions. The finding that there is no significant difference for CXCL12and CXCR4expression among different histological types indicate that the different histological type NSCLCs possibly have mutual origins.2. The detection of CXCL12together with CXCR4is worth judging lung cancer invasion and metastasis. And this may serve as prognostic indicators and guide the clinical treatment.