title: Identification of PRDX4 and P4HA2 as metastasis-associated proteins in oral cavity squamous cell carcinoma by comparative tissue proteomics of microdissected specimens using iTRAQ technology.
abstract: Cervical lymph node metastasis represents the major prognosticator for oral cavity squamous cell carcinoma (OSCC). Here, we used an iTRAQ-based quantitative proteomic approach to identify proteins that are differentially expressed between microdissected primary and metastatic OSCC tumors. The selected candidates were examined in tissue sections via immunohistochemistry, and their roles in OSCC cell function investigated using RNA interference. Seventy-four differentially expressed proteins in nodal metastases, including PRDX4 and P4HA2, were identified. Immunohistochemical analysis revealed significantly higher levels of PRDX4 and P4HA2 in tumor cells than adjacent non-tumor epithelia (P < 0.0001 and P < 0.0001, respectively), and even higher expression in the 31 metastatic tumors of lymph nodes, compared to the corresponding primary tumors (P = 0.060 and P = 0.002, respectively). Overexpression of PRDX4 and P4HA2 was significantly associated with positive pN status (P = 0.048 and P = 0.021, respectively). PRDX4 overexpression was a significant prognostic factor for disease-specific survival in both univariate and multivariate analyses (P = 0.034 and P = 0.032, respectively). Additionally, cell migration and invasiveness were attenuated in OEC-M1 cells upon in vitro knockdown of PRDX4 and P4HA2 with specific interfering RNA. Novel metastasis-related prognostic markers for OSCC could be identified by our approach.
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan.
authors.forename: Kai-Ping
authors.initials: KP
authors.lastname: Chang
authors.forename: Jau-Song
authors.initials: JS
authors.lastname: Yu
authors.forename: Kun-Yi
authors.initials: KY
authors.lastname: Chien
authors.forename: Chien-Wei
authors.initials: CW
authors.lastname: Lee
authors.forename: Ying
authors.initials: Y
authors.lastname: Liang
authors.forename: Chun-Ta
authors.initials: CT
authors.lastname: Liao
authors.forename: Tzu-Chen
authors.initials: TC
authors.lastname: Yen
authors.forename: Li-Yu
authors.initials: LY
authors.lastname: Lee
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Huang
authors.forename: Shiau-Chin
authors.initials: SC
authors.lastname: Liu
authors.forename: Yu-Sun
authors.initials: YS
authors.lastname: Chang
authors.forename: Lang-Ming
authors.initials: LM
authors.lastname: Chi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality / Q000556:secondary*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002853:Chromatography, Liquid; D006801:Humans; D053208:Kaplan-Meier Estimate; D061346:Laser Capture Microdissection; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D054464:Peroxiredoxins / Q000235:genetics / Q000378:metabolism*; D011393:Procollagen-Proline Dioxygenase / Q000235:genetics / Q000378:metabolism*; D016016:Proportional Hazards Models; D020543:Proteome / Q000235:genetics / Q000378:metabolism; D053719:Tandem Mass Spectrometry; D015854:Up-Regulation
chemical_list: D009363:Neoplasm Proteins; D020543:Proteome; C515980:PRDX4 protein, human; D054464:Peroxiredoxins; D011393:Procollagen-Proline Dioxygenase