基質?屬蛋白?-11基因多型性對大腸直腸癌病程發展及臨床病理特徵的影響

大腸直腸癌 (Colorectal Cancer, CRC) 是全球癌症死亡排名第三，同樣在臺灣也是十大癌症發生率及死亡率排行前幾名。基質金屬蛋白?-11 (matrix metalloproteinase-11, MMP-11) 是 MMP 家族其中一種蛋白水解?，主要功能是負責參與細胞外基質 (Extracellular matrix, ECM) 降解和組織重塑；越來越多的證據證明，基質金屬蛋白?-11可以對癌症發展表現出促進的作用。在這項研究中，我們評估了479名CRC患者和479名無癌症對照者作為研究MMP-11基因多型性與大腸直腸癌的相關性。我們發現了MMP-11 SNP rs738792 (TC+CC) 基因型者會有較高的傾向發展為大腸直腸癌，而在男性大腸直腸癌患者中，帶有MMP-11 SNP rs131451 (TC+CC) 基因型者，會與發展成較大腫瘤及神經周圍侵襲呈正相關。此外，對照癌症基因組圖譜 (TCGA) 的分析顯示出與正常組織相比，大腸直腸癌患者癌症組織的 MMP-11 水平明顯上升，並且與癌症晚期、較大的腫瘤和淋巴結轉移相關。基因型組織數據庫 (GTEx) 也顯示，MMP-11 SNP rs738792(CC)與(CT)基因型變異體的 MMP-11 表現高於(TT)基因型。總之，我們的結果顯示MMP-11的基因多型性與大腸直腸癌的發病率和進展有相關性。

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. Mounting evidence has demonstrated that MMP-11 can have promotive effects on cancer development. In this study, the link of MMP-11 gene polymorphisms to Colorectal cancer was assessed between 479 CRC patients and 479 cancer-free subjects. We found that the MMP-11 SNP rs738792 (TC+CC) genotype was more inclined to develop CRC, The MMP-11 rs131451 (TC+CC) genotypic variants were correlated with greater tumor T status and perineural invasion 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 indicate an association between MMP-11 gene polymorphisms and the incidence and progression of colorectal cancer.