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

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.

Soluble stroma‐related biomarkers of pancreatic cancer

“…our study for the first time demonstrates its utility as a circulating PDAC biomarker in patients (Bennewith et al, 2009;Neesse et al, 2011). Both MMP7 and CCN2 have been associated with poor prognosis in different types of cancer (Klupp et al, 2016;Sun et al, 2017) and with fibrotic or inflammatory diseases (Dendooven et al, 2011;Irvine et al, 2016). However, our results suggest that an improvement in the specificity of MMP7 and CCN2 results from the inclusion of additional biomarkers.…”

“…Both MMP7 and CCN2 have been associated with poor prognosis in different types of cancer (Klupp et al , ; Sun et al , ) and with fibrotic or inflammatory diseases (Dendooven et al , ; Irvine et al , ). However, our results suggest that an improvement in the specificity of MMP7 and CCN2 results from the inclusion of additional biomarkers.…”

Failed immune responses across multiple pathologies share pan-tumor and circulating lymphocytic targets

“…In cancer, MMP-9 is associated with genetic instability, tissue remodeling, tumor cell proliferation, invasion and motility, progression, extravasation, metastasis, epithelial-mesenchymal transition, angiogenesis, apoptosis, inflammation, and immunosurveillance (36). MMP-9 in PBLs, serum, and tumors predicts prognosis, invasiveness, grade and differentiation, recurrence, metastasis, and treatment resistance, for bladder, lung, blood, colorectal, prostate, and liver cancers (42)(43)(44)(45)(46)(47)(48)(49). In patients with RCC, MMP-9 is increased in tumors and plasma (50) and correlates with histological grade (51), poor prognosis, and lowered survival (52), metastasis, decreased time to progression, and poor response to sunitinib (53).…”

Potential Therapeutic Value of Mangiferin for Lung Adenocarcinoma (Luad): A Comprehensive Study Based on in Vitro Experiments and Bioinformatics

“…The genovariation of DAB2IP/AIP1 is related to increasing the risk of lung cancer in Chinese males [62]. Similarly, another study revealed that an elevated circulating tumor cell count and overexpression of MMP7 correlate with metastasis and clinical progression in LUAD patients [63]. However, most of the signi cant genes predicted in our study, which are related to neither LUAD nor mangiferin, still lack literature validation, and the regulatory mechanism governing the lncRNA-mRNA pairs warrants further exploration.…”