Identification of potential lung cancer biomarkers using an in vitro carcinogenesis model

다국어 초록 (Multilingual Abstract)

Lung cancer is one of the deadliest and commonly diagnosed
neoplasms. Early diagnosis of this disease is
critical for improving clinical outcome and prognosis.
Because the early stages of lung cancer often produce
no symptoms, it is necessary to identify biomarkers for
early detection, prognostic evaluation, and recurrence
monitoring of the cancer. To identify potential lung
cancer biomarkers, we analyzed the differential protein
secretion from transformed bronchial epithelial
cells (1198 and 1170-I) as compared to immortalized
normal bronchial epithelial cells (BEAS-2B) and
non-transformed cells (1799) all of which are derived
from BEAS-2B and represent multistage bronchial epithelial
carcinogenesis. The proteins recovered from
the conditioned media of the cells were separated on
two-dimensional gels. There was little difference between the secretome of the BEAS-2B and 1799 cells,
whereas the patterns between the transformed 1198
and 1170-I cells and non-transformed 1799 cells were
significantly different. Using mass spectrometry and
database search, we identified 20 proteins including
protein gene product 9.5 (PGP9.5), translationally controlled
tumor protein (TCTP), tissue inhibitors of metalloproteinases-
2 (TIMP-2), and triosephosphate isomerase
(TPI), that were either increased or decreased
simultaneously in conditioned media of both 1198 and
1170-I cells. Furthermore, levels of PGP9.5, TCTP,
TIMP-2, and TPI were significantly increased not only
in the conditioned media of both transformed cell lines
when compared to those of BEAS-2B and 1799 cells,
but also in plasmas and tissues from lung cancer patients
when compared to those in normal controls. We
suggest the PGP9.5, TCTP, TIMP-2, and TPI as promising
candidates for lung cancer serum biomarkers.

다국어 초록 (Multilingual Abstract)

Lung cancer is one of the deadliest and commonly diagnosed
neoplasms. Early diagnosis of this disease is
critical for improving clinical outcome and prognosis.
Because the early stages of lung cancer often produce
no symptoms, it is necessary to identify biomarkers for
early detection, prognostic evaluation, and recurrence
monitoring of the cancer. To identify potential lung
cancer biomarkers, we analyzed the differential protein
secretion from transformed bronchial epithelial
cells (1198 and 1170-I) as compared to immortalized
normal bronchial epithelial cells (BEAS-2B) and
non-transformed cells (1799) all of which are derived
from BEAS-2B and represent multistage bronchial epithelial
carcinogenesis. The proteins recovered from
the conditioned media of the cells were separated on
two-dimensional gels. There was little difference between the secretome of the BEAS-2B and 1799 cells,
whereas the patterns between the transformed 1198
and 1170-I cells and non-transformed 1799 cells were
significantly different. Using mass spectrometry and
database search, we identified 20 proteins including
protein gene product 9.5 (PGP9.5), translationally controlled
tumor protein (TCTP), tissue inhibitors of metalloproteinases-
2 (TIMP-2), and triosephosphate isomerase
(TPI), that were either increased or decreased
simultaneously in conditioned media of both 1198 and
1170-I cells. Furthermore, levels of PGP9.5, TCTP,
TIMP-2, and TPI were significantly increased not only
in the conditioned media of both transformed cell lines
when compared to those of BEAS-2B and 1799 cells,
but also in plasmas and tissues from lung cancer patients
when compared to those in normal controls. We
suggest the PGP9.5, TCTP, TIMP-2, and TPI as promising
candidates for lung cancer serum biomarkers.

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