Dysregulation of
protein expression is associated with most diseases including
cancer. MS-based proteomic analysis is widely employed as a tool to study
protein dysregulation in
cancers.
Proteins that are differentially expressed in
head and neck squamous cell carcinoma (
HNSCC) cell lines compared to the normal oral cell line could serve as
biomarkers for patient stratification. To understand the proteomic complexity in
HNSCC, we carried out iTRAQ-based MS analysis on a panel of
HNSCC cell lines in addition to a normal oral keratinocyte cell line. LC-MS/MS analysis of total
proteome of the
HNSCC cell lines led to the identification of 3263
proteins, of which 185
proteins were overexpressed and 190
proteins were downregulated more than twofold in at least two of the three
HNSCC cell lines studied. Among the overexpressed
proteins, 23
proteins were related to DNA replication and repair. These included high-mobility group box 2 (
HMGB2) protein, which was overexpressed in all three
HNSCC lines studied. Overexpression of
HMGB2 has been reported in various
cancers, yet its role in
HNSCC remains unclear. Immunohistochemical labeling of
HMGB2 in a panel of
HNSCC tumors using tissue microarrays revealed overexpression in 77% (54 of 70) of
tumors. The
HMGB proteins are known to bind to
DNA structure resulting from
cisplatin-
DNA adducts and affect the chemosensitivity of cells. We observed that
siRNA-mediated silencing of
HMGB2 increased the sensitivity of the
HNSCC cell lines to
cisplatin and
5-FU. We hypothesize that targeting
HMGB2 could enhance the efficacy of existing chemotherapeutic regimens for treatment of
HNSCC. All MS data have been deposited in the ProteomeXchange with identifier PXD000737 (http://proteomecentral.proteomexchange.org/dataset/PXD000737).