The Impact of Matrix Metalloproteinase-11 Polymorphisms on Colorectal Cancer Progression and Clinicopathological Characteristics

Abstract

Colorectal cancer (CRC) is the third most common cause of cancer mortality worldwide and the most prevalent cancer in Taiwan. The matrix metalloproteinase (MMP)-11 is a proteolytic enzyme of the MMP family which is involved in extracellular matrix degradation and tissue remodeling. In this study, we focused on the associations of MMP-11 single-nucleotide polymorphisms (SNPs) with CRC susceptibility and clinicopathological characteristics. The MMP-11 SNPs rs131451, rs738791, rs2267029, rs738792, and rs28382575 in 479 controls and 479 patients with CRC were analyzed with real-time polymerase chain reaction. We found that the MMP-11 SNP rs738792 “TC + CC” genotype was significantly associated with perineural invasion in colon cancer patients after controlling for clinical parameters [OR (95% CI) = 1.783 (1.074–2.960); p = 0.025]. The MMP-11 rs131451 “TC + CC” genotypic variants were correlated with greater tumor T status [OR (95% CI):1.254 (1.025–1.534); p = 0.028] and perineural invasion [OR (95% CI):1.773 (1.027–3.062); p = 0.040) in male CRC patients. Furthermore, analyses of The Cancer Genome Atlas (TCGA) revealed that MMP-11 levels were upregulated in colorectal carcinoma tissue compared with normal tissues and were correlated with advanced stage, larger tumor sizes, and lymph node metastasis. Moreover, the data from the Genotype-Tissue Expression (GTEx) database exhibited that the MMP-11 rs738792 “CC” and “CT” genotypic variants have higher MMP-11 expression than the “TT” genotype. In conclusion, our results have demonstrated that the MMP-11 SNPs rs738792 and rs131451 may have potential to provide biomarkers to evaluate CRC disease progression, and the MMP-11 rs131451 polymorphism may shed light on sex discrepancy in CRC development and prognosis.