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Page 8 of 13 Udukala et al. J Cancer Metastasis Treat 2020;6:25 I http://dx.doi.org/10.20517/2394-4722.2020.45

Figure 6. Box plots (indicating the observed data range) for matrix metalloproteinase MMP7 and MMP9. The groups are apparently
healthy control group (n = 20), non-small cell lung cancer stage 1 (n = 9), non-small cell lung cancer stage 2 (n = 12), and non-small cell
lung cancer stage 3 (n = 12). *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001. All biospecimens were obtained from the South Eastern
Nebraska Cancer Center. Non-small cell lung cancers had been staged according to the American Joint Committee on Cancer TNM
staging system [2]

Figure 7. Box plots (indicating the observed data range) for matrix metalloproteinase 13. The groups are apparently healthy control group
(n = 20), non-small cell lung cancer stage 1 (n = 9), non-small cell lung cancer stage 2 (n = 12), and non-small cell lung cancer stage 3
(n = 12). *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001; n.s.: not significant. All biospecimens were obtained from the South Eastern
Nebraska Cancer Center. Non-small cell lung cancers had been staged according to the American Joint Committee on Cancer TNM
staging system [2]

in fluorescence. Similar to cathepsin B, uPA was well suited for NSCLC staging but not for early cancer
detection. A very different type of dependence of nanobiosensor fluorescence on NSCLC staging was
observed for MMP1 activity, which was significantly increased starting at stage 1! However, it did not
change significantly when progressing to stages 2 and 3. This finding makes MMP1 our best biomarker for
very early diagnosis of NSCLC.

In contrast to MMP1 and very similar to cathepsin L, the protease activities of MMP2, MMP3, MMP7, and
MMP9 in the serum of NSCLC patients increased steadily with escalating cancer stage [Figures 5 and 6].