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In the omics era, the development of high-throughput technologies
that permit the solution of deciphering cancer from higher
dimensionality provides a knowledge base that changes the face
of cancer understanding and therapeutics (Cho, 2010b). Serum is
one of the most easily procured patient specimens and it is
perceived to contain many of the molecules that might indicate
systemic function. Thus, serum is the sample source that is most
often profiled in the hopes of identifying sets of biomarkers for
clinical use (Gilbert et al, 2004).
In this study, proteomic analyses of serum samples from
patients with lung cancer and controls have identified SAA as an
elevated biomarker in lung cancer (as shown by SELDI analysis
and confirmed by immunoassay). It is known that SAA is secreted
during the acute phase of inflammation; the conservation of this
protein throughout invertebrates and vertebrates suggests that
SAA has an essential role in all animals including humans (Manley
et al, 2006). There are several functions of SAA protein, describedin the context of inflammation, that are compatible with the
mechanism of tumour invasion and metastasis. These properties
place SAA as an extracellular matrix-associated adhesion protein
with a potential role in tumour pathogenesis. The SAA mRNA
expression in epithelial cells was gradually increased as they
progressed through different stages of dysplasia to overt carcinoma
(Gutfeld et al, 2006). Accumulating evidence has suggested that
SAA might be used to detect a pattern of physiological events that
reflect the growth of malignancy and host response. Elevated SAA
may be a primary product of tumour lesions, but can also be the
product of hepatocytes. Further investigation to determine
whether cancer tissue-derived cytokines stimulate SAA synthesis
in liver or epithelial cells will be interesting (Malle et al, 2009).
Overexpression of SAA has been reported in nasopharyngeal,
renal, gastric, hepatocellular, melanoma, breast, and endometrial
cancers (Cho et al, 2004; Tolson et al, 2004; Chan et al, 2007;
He et al, 2008; Findeisen et al, 2009; Pierce et al, 2009; Ramankulov
et al, 2008; Cocco et al, 2009, 2010; Sasazuki et al, 2010; Vermaat
et al, 2010). Our study not only detected increased SAA level in the
serum of lung cancer patients but also identified that elevated SAA
level may be a non-invasive biomarker, useful for the prediction of
lung cancer prognosis. As far as we know, the association of SAA
with the survival of lung cancer patients has never been reported.
Moreover, a number of SELDI peaks were found to be significantly
differentiated between the serum of cancer patients and controls,
as well as between the poor prognosis patients and good prognosis
patients. Further identification of these peaks is awaiting.
Recently, the US Food and Drug Administration has approved
an ovarian cancer triage test called OVA1, containing CA125 and
four biomarkers (b2-microglobulin, transferrin, apolipoprotein A1,
and transthyretin) identified by SELDI-TOF-MS (Fung, 2010). This
marks an encouraging step of translating biomarker discovery
from laboratory to clinic. It showed that having identified
biomarkers by primary screening, a standard assay may then be
developed and finally converted into clinically applicable measures.
Our results reveal that the level of SAA is highly elevated in
lung cancer and in the patients with poor prognosis, thus
warranting further studies investigating this candidate biomarker
as part of a multimarker test for the diagnosis and prognosis of
lung cancer.
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