Abstract: Lung adenocarcinoma (LADC) is among the most malignant cancers that frequently develops micrometastases even in early stages of the disease. Circulating tumor cell (CTC) number, matrix metalloproteinase (MMP) 7, and MMP9 show great prospects as predictive biomarkers in many tumors. However, the interactions between these biomarkers and the molecular basis of their roles in the metastasis and prognosis of LADC remain unclear. The present study revealed that an elevated CTC count and overexpression of MMP7 and MMP9 correlate with metastasis and clinical progression in LADC patients (n=143). Furthermore, MMP7 and MMP9 upregulation facilitates LADC cell migration in vitro and enhances serum CTC levels in a xenograft mouse model. More importantly, receiver operating characteristic (ROC) curves and Kaplan–Meier analysis confirmed more accurate prediction of metastasis and overall survival (OS) with a combination panel of CTC, MMP7, and MMP9. Taken together, our data show, for the first time, the involvement of MMP7 and MMP9 in the release of CTCs into the peripheral blood, and our data reveal that CTC count and expression of MMP7 and MMP9 can be used together as an effective clinical prediction panel for LADC metastasis and prognosis.
Keywords: lung adenocarcinoma, circulating tumor cell, MMP7/MMP9, metastasis, prognosis