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NanoVelcro-captured CTC number concomitant with enhanced serum levels of MMP7 and MMP9 enables accurate prediction of metastasis and poor prognosis in patients with lung adenocarcinoma

Authors Sun Y, Chen Y, Li S, Lei Y, Xu D, Jiang N, Zhang Y, Cao J, Ke Z

Received 15 June 2017

Accepted for publication 28 July 2017

Published 31 August 2017 Volume 2017:12 Pages 6399—6412

DOI https://doi.org/10.2147/IJN.S144033

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Thiruganesh Ramasamy

Peer reviewer comments 2

Editor who approved publication: Professor Dongwoo Khang


Yu Sun,1,* Yangshan Chen,1,* Shuhua Li,1,* Yiyan Lei,2 Di Xu,3 Neng Jiang,1 Yang Zhang,4 Jessica Cao,5 Zunfu Ke1,*

1Department of Pathology, 2Department of Thoracic Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 3Department of Thoracic Surgery, The Central Hospital of Wuhan, Wuhan, Hubei, People’s Republic of China; 4Biomedical Engineering, The University of Texas at El Paso, El Paso, TX, USA; 5Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada

*These authors contributed equally to this work

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
 

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