Copy number variations of MMP-9 are prognostic biomarkers for hepatocellular carcinoma

Xi Yu, Jing Huang, Shengdong Wu, Yi Huang, Yuying Shan, Caide Lu


Background: This study aimed to investigate the effect of matrix metalloproteinase-9 (MMP-9) copy number variations (CNVs) on hepatocellular carcinoma (HCC) poor prognosis and recurrence.
Methods: A total of 35 patients were collected between January 2016 and December 2018. The copy number and expression level of MMP-9 were measured in 35 HCC tumor tissues and 35 paired adjacent non-tumor tissues using digital polymerase chain reaction (dPCR) and quantitative reverse transcription polymerase chain reaction (RT-qPCR), respectively.
Results: Our results showed that MMP-9 expression was significantly upregulated in HCC tumor tissues compared to adjacent non-tumor tissues (5.521±9.545 versus 1.000±0.000, P=0.0047). Interestingly, MMP-9 CNVs only existed in tumor tissues (15/35 versus 0/35, P=0.002). A breakdown analysis by the occurrence of CNVs in tumor tissues had shown that there were significant differences between CNVs group and non-CNVs group in the expression levels of tissue alpha-fetoprotein (AFP) (P=0.015), tumor size (P<0.001), differentiation (P<0.001), microvascular invasion (MVI) (P=0.009), and clinical stage (P<0.001). Receiver operating characteristic (ROC) curves showed that MMP-9 CNVs and expression were significant predictors of HCC [P<0.0001, area under the curve (AUC) =0.76].
Conclusions: Our results demonstrated that MMP-9 CNVs were a promising diagnostic biomarker for HCC.