Significance Of GLUT-1 And CA-9 Expression In Metastatic Renal Cell Carcinoma

Objective Metastatic renal cell carcinoma(m RCC) is generally unresponsive to conventional chemotherapy and hormonal therapy now, and treatment with cytokines results in an only modest response rate. In recent years, targeted therapies have improved the prognosis of m RCC.Understanding and identifying prognostic factors are important for the evelopment and evaluation of new treatments. So far, however, factors predictive for OS with targeting agents have not been fully assessed, especially in China.We wanted to identify the prognostic factors for OS in Chinese patients with m RCC treated with targeted therapy with the help of understanding the significance of GLUT-1 and CA-9 expression in metastatic renal cell carcinoma.Contents and Methods In this hospital-based case-control study, renal cell carcinoma samples were obtained from 48 patients with m RCC and 27 controls with normal kidney tissues.Then we used immunohistochemistry for detection of GLUT-1 and CA-9 expression in the samples. Statistical analysis was conducted using the Package SPSS 17.0 for Windows. Fisher’s exact test was used to compare correlates between GLUT-1 and CA-9 expression in the different samples and the risk of m RCC. We explored the relationship between the results of GLUT-1 and CA-9 expression and renal cell carcinoma staging and grading by fisher’s exact test. The OS was calculated by the Kaplan-Meier method. Each variable was investigated univariately and then multivariately using a stepwise algorithm. A multivariate Cox regression model analyzed baseline variables for prognostic significance. All statistical tests were2-sided and P< 0.05 was considered statistically significant.Results1. Expression of GLUT-1 and CA-9 between renal cell carcinoma tissue and normal kidney tissueIn 48 cases of renal cell carcinoma tissue samples, the positive expression of GLUT-1 is 25 cases, accounting for 52.1%. Normal kidney tissue samples was 27 cases, and positive expression of GLUT-1 is 6 cases, accounting for 22.2%. The positive expression of CA-9 is 22 cases in renal cell carcinoma tissue samples,accounting for 45.8% and positive expression of CA-9 is 3 cases in normal samples,accounting for 11.1%. Fisher’s exact test was used to compare positive rate of the two samples. In kidney cancer samples, the positive expression rates of GLUT-1 and CA-9 were much bigger than it in the normal kidney tissues and the two expression differences were statistically significant(P=0.015< 0.05, P=0.002< 0.05).2. Association between expression of GLUT-1 and CA-9 in kidney cancer tissue and pathological staging or grading Spearman correlation analysis revealed that no statistically significant differences were found between the expression of GLUT-1 and pathological staging or grading of m RCC(P= 0.747 > 0.05, P= 0.228 > 0.05). We also found that there was no correlation between the expression of CA-9 and p TNM staging of m RCC.Statistically significant difference was found between the expression of CA-9 and pathological grading of m RCC,and the correlation of the two indicators was negative(r =- 0.296,P= 0.041< 0.05).3. Association between expressing of GLUT-1 and CA-9 in carcinoma tissue and the prognosis of m RCC We analized the expressing rates of GLUT-1 and CA-9 in carcinoma tissue of two groups by the way of using Fisher’s exact test. In kidney cancer samples, the positive expression rate of GLUT-1 was much bigger than it in the normal group(P=0.015<0.05)and the positive expression rate of CA-9 in experimental group was much bigger than it in normal group,too(P=0.002< 0.05).While the expression level of GLUT-1was negatively correlated with the survival rates of patients with m RCC, and the survival rates of patients with m RCC was positively correlated with expression level of CA-9.4. Prognostic factors for overall survival with targeted therapy in patients with metastatic renal cell carcinoma Univariate analysis identifid signifiant negative prognostic factors(p< 0.05) asECOG performance status ≥2, positive expression of GLUT-1, negative expression of CA-9, higher level of p TNM stage, time from diagnosis to start of systemic therapy of < 1 year, symptoms, microscopic necrosis, ≥2 metastatic sites, presence of bone metastasis, as well as a relative dose intensity of targeting agents in the fist month(1M-RDI) of < 50%. Subsequent multivariate analysis found 4 baseline characteristics that were independently predictive for investigator-assessed OS in m RCC patients treated with targeted therapy. These 4 variables were: absence of symptoms, absence of microscopic necrosis in the tumor, negative expression of GLUT-1, and targeting agent 1M-RDI of ≥50%.Conclusions In renal cell carcinoma tissues and normal kidney tissues, both GLUT-1 and CA-9were expressed in the samples. In kidney cancer tissues, the positive expression rates of GLUT-1 and CA-9 were much bigger than it in the normal group. The results showed that bigger expressing rates of GLUT-1 and CA-9 in renal cell carcinoma tissue will lead to appear m RCC more easily. There was no association between GLUT-1 and pathological stages of m RCC, but CA-9 was opposite. Statistically significant difference was noticed between the expression of CA-9 and pathological grading of m RCC, and the correlation of the two indicators was negative. Subsequent multivariate analysis found 4 baseline characteristics that were independently predictive for investigator-assessed OS in m RCC patients treated with targeted therapy. These 4 variables were: absence of symptoms, absence of microscopic necrosis in the tumor, negative expression of GLUT-1, and targeting agent 1M-RDI of≥50%.