Lung cancer
Increased levels of various MMPs, such as MMP-1, MMP-2,
MMP-7, MMP-12, MMP-13, and MMP-26, have been found
in tissues from lung cancer patients [53–57]. High levels of
MMP-1 in the blood or cancer tissue have been associated
with increased risk of metastases and poorer survival rates [53,
58]. In a recent systematic meta-analyses of published articles
about the relationship between MMP-2 and overall survival in
1,439 patients with non-small cell lung cancer (NSCLC), the
authors found that strong immunohistochemical staining for
MMP-2 in tumor tissue predicted poorer patient survival [59].
Reports regarding the prognostic value of MMP-9 in blood or
cancer tissue are contradictive, irrespective of detection tech-
nique. Whereas several studies report no prognostic value
[60–64], others find high MMP-9 expression to be associated
with poor prognosis [65–69]. A newly published meta-
analyses of 1,946 NSCLC cases from 15 studies concluded
that patients with tumors that had positive immunohistochem-
ical staining for MMP-9 showed poorer survival rates than
patients with negative staining for MMP-9 in the tumors [70].
Furthermore, a study examining a classifier including several
potential lung cancer markers, among them MMP-2, MMP-9,
TIMP-1, and TIMP-2, found the classifier to be an indepen-
dent predictor of overall survival [71]. High serum levels of
TIMP1 has also been found to predict poor survival in lung
cancer patients [68], whereas a later study by the same group
found that strong immunohistochemical TIMP-1 staining in
tumor tissue from lung cancer patients was associated with
favorable prognosis though not statistically significant [66]. In
patients with NSCLC, strong immunohistochemical staining
for MMP-7 in tumor was significantly associated with lower
overall survival [72, 73], whereas a previous study found no
correlation [61]. High expression of MMP-12, MMP-13, and
MMP-26 is also reported to predict poorer overall survival in
NSCLC patients [54–56]. The prognostic value of MMP-12
was increased when the expression level of serine protease
uPA also was considered [54].