Correlation between CXCR4 and MMP-2 Expression with T Stage in Clear Cell Renal Cell Carcinoma

Abstract

Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer with high mortality. Escalation of T stage associates with worse survival. Proper and significant biomarker examination necessary to determine the predictive factor and the opportunity of targeted therapy as well. Upregulated CXCR4 expression on cancer cell promotes its aggressive growth, dissemination, metastasis, and conventional therapy resistance. Overexpression of CXCR4 may induce MMP-2 activity on tumor cell, an enzyme that degrade extracellular matrix and basal membrane particularly, which associated with tumor invasion and metastasis. Those biomarkers activity might be advantaged under hypoxic microenvironment in ccRCC. This study aimed to analyze the role and correlation of CXCR4 and MMP-2 expression with various T stages in ccRCC. Analytic observational study with cross-sectional approach was conducted on 43 formalin-fixed paraffin-embedded tissue of patients diagnosed as ccRCC in Anatomical Pathology Laboratory of Dr. Soetomo Hospital throughout January 2015 until December 2020. CXCR4 and MMP-2 expression were evaluated by immunohistochemistry. Statistical analysis with Kruskal-Wallis and Spearman test were utilized to analyze the expression difference and correlation. Difference of both CXCR4 (p=0.016) and MMP-2 (p=0.029) expression were obtained on various T stages. There was a significant positive correlation between CXCR4 expression (p=0.001) and MMP-2 expression (p=0.002) with T stage, also between CXCR4 with MMP-2 expression in various T stage of ccRCC (p=0.000). In conclusion, this study exhibited that CXCR4 and MMP-2 expression showed synergistic and positive correlation with T stage and might be considered as the basis of targeted therapy in ccRCC.