The MMP9:TIMP3 transcript ratio was significantly increased in NSCLC and using receiver operating characteristic curve analysis accurately discriminated malignant and benign bronchoscopy specimens (area under the curve = 0.98; 95% CI, 0.93-1; P < 0.0001).
Two microRNAs, miR-221 and miR-222, upregulated by the MET proto-oncogene, have been already described to enhance cell survival and to induce TNF-related apoptosis-inducing ligand (TRAIL) resistance in NSCLC cell lines, through the downregulation of p27(kip1), PTEN and TIMP3.
In summary, loss of TIMP-3 may increase IL-6 production via the tumor necrosis factor α/nuclear factor κB axis, thereby promoting tumor malignancy and subsequent relapse and poor survival in patients with HPV-infected non-small cell lung cancer.
To determine the relationship between the methylation status of the tumor suppressor and the tumor-related genes, and the clinicopathologic characteristics, including the survival rate, in patients with NSCLC after a surgical resection, we studied methylation in 10 genes (DAPK, FHIT, H-cadherin, MGMT, p14, p16, RAR-beta, RASSF1A, RUNX3, and TIMP-3) in 101 NSCLC cases by methylation-specific PCR (MSP).