Secretome Profiling of Primary Cells Reveals That THBS2 Is a Salivary Biomarker of Oral Cavity Squamous Cell Carcinoma

Oral
cavity squamous cell carcinoma (OSCC), which is a leading
cause of cancer-related death worldwide, is frequently associated
with poor prognosis and mortality. The discovery of body fluid-accessible
biomarkers may help improve the detection of OSCC. In the present
work, we established primary cell cultures derived from OSCC and adjacent
noncancerous epithelium and performed comparative profiling of their
secretomes. Using spectral counting-based label-free quantification,
we found that 64 proteins were significantly higher in primary OSCC
cells compared with primary adjacent noncancerous cells. We then retrieved
the mRNA expression levels of these 64 proteins in oral cavity tumor
and noncancerous tissues from public domain array-based transcriptome
data sets and used this information to prioritize the biomarker candidates.
We identified 19 candidates; among them, the protein levels of THBS2,
UFD1L, and DNAJB11 were found to be elevated in OSCC tissues compared
with adjacent noncancerous epithelia. Importantly, higher levels of
THBS2 in OSCC tissues were associated with a higher overall pathological
stage, positive perineural invasion, and a poorer prognosis. Moreover,
the salivary levels of THBS2 in OSCC patients were elevated compared
to those of noncancer controls. Our results collectively indicate
that analysis of the primary cell secretome is a feasible strategy
for biomarker identification, and that THBS2 is a potentially useful
salivary marker for the detection of OSCC.