2D-DIGE proteomic characterization of head and neck squamous cell carcinoma.
2D-DIGE proteomic characterization of head and neck squamous cell carcinoma.
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DOI：
10.1016/j.otohns.2009.08.011
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发表时间：
2009-11
影响因子：
3.4
通讯作者：
Dynan, William S.
中科院分区：
文献类型：
--
作者：
Merkley, Mark A.;Weinberger, Paul M.;Jackson, Lana L.;Podolsky, Robert H.;Lee, Jeffrey R.;Dynan, William S.
Identify proteins that are differentially expressed between head and neck squamous cell cancer and patient-matched normal adjacent tissue, and validate findings in a separate patient cohort. Cross-sectional study of surgical specimens. Tertiary care academic medical center. Laser capture microdissection and two-dimensional difference gel electrophoresis were used previously to establish proteomic profiles for tumor and normal adjacent tissue from 14 patients. Here, significance analysis of microarray was used to rank candidate biomarkers. Spots meeting statistical and biological criteria of significance were analyzed by liquid chromatography and tandem mass spectrometry to obtain protein identifications. The expression pattern of the highest-ranked candidate biomarker (cornulin) was validated in a larger, independent patient cohort (n=68) by immunohistochemical staining of a tissue microarray. 117/732 spots (15.9%) met criteria for significance. Identities were obtained for 40 spots, representing 19 different proteins. Four proteins were novel in the context of HNSCC: glutathione synthetase, which was upregulated, and cornulin (SEP53), guanylate binding protein 6, and GRP78, which were downregulated. Cornulin functions in the stress response in normal squamous epithelium, and reduced expression has been proposed as a marker of susceptibility to laryngopharyngeal reflux and other stressors. Loss of cornulin expression was confirmed in an independent HNSCC patient cohort (P<.001). Downregulation of cornulin is a prominent feature of the molecular signature of HNSCC identified by comparative proteomics. Cornulin may represent a link between HNSCC and other pathologies arising in stratified squamous epithelium.
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