Mapping Conformational Changes in the Saliva Proteome Potentially Associated with Oral Cancer Aggressiveness

Diverse proteomics-based strategies have been applied
to saliva
to quantitatively identify diagnostic and prognostic targets for oral
cancer. Considering that these targets may be regulated by events
that do not imply variation in protein abundance levels, we hypothesized
that changes in protein conformation can be associated with diagnosis
and prognosis, revealing biological processes and novel targets of
clinical relevance. For this, we employed limited proteolysis–mass
spectrometry in saliva samples to explore structural alterations,
comparing the proteome of healthy control and oral squamous cell carcinoma
(OSCC) patients with and without lymph node metastasis. Thirty-six
proteins with potential structural rearrangements were associated
with clinical patient features including transketolase and its interacting
partners. Moreover, N-glycosylated peptides contribute
to structural rearrangements of potential diagnostic and prognostic
markers. Altogether, this approach utilizes saliva proteins to search
for targets for diagnosing and prognosing oral cancer and can guide
the discovery of potential regulated sites beyond protein-level abundance.