Comparative proteomics approach to screening of potential diagnostic and therapeutic targets for oral squamous cell carcinoma.
This work demonstrates that a comprehensive strategy of proteomics identification combined with further validation and detailed functional analysis should be adopted in the field of cancer biomarker discovery. A comparative proteomics approach was utilized to identify differentially expressed proteins in 10 oral squamous carcinoma samples paired with their corresponding normal tissues. A total of 52 significantly and consistently altered proteins were identified with eight of these being reported for the first time in oral squamous carcinoma. Of the eight newly implicated proteins, RACK1 was chosen for detailed analysis. RACK1 was demonstrated to be up-regulated in cancer at both the mRNA and protein levels. Immunohistochemical examination showed that the enhanced expression of RACK1 was correlated with the severity of the epithelial dysplasia as well as clinical stage, lymph node involvement, and recurrence, which are known indicators of a relatively poor prognosis in oral squamous carcinoma patients. RNA interference specifically targeted to silence RACK1 could initiate apoptosis of oral squamous carcinoma cells. Taken together, the results indicate that RACK1 is up-regulated in oral squamous carcinoma, not only being closely related to cell proliferation and apoptosis but also linked to clinical invasiveness and metastasis in carcinogenesis. The observations suggest that RACK1 may be a potential biomarker for early diagnosis, prognosis, and monitoring in the therapy of oral squamous carcinoma. Further this comprehensive strategy could be used for identifying other differentially expressed proteins that have potential to be candidate biomarkers of oral squamous carcinoma.
Wang
Zhi
Z
State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Chengdu 610041, Sichuan, China.
Jiang
Lu
L
Huang
Canhua
C
Li
Zhengyu
Z
Chen
Lijuan
L
Gou
Lantu
L
Chen
Ping
P
Tong
Aiping
A
Tang
Minghai
M
Gao
Feng
F
Shen
Jun
J
Zhang
Yuanyuan
Y
Bai
Jingping
J
Zhou
Min
M
Miao
Di
D
Chen
Qianming
Q
D000595:Amino Acid Sequence; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000473:pathology / Q000628:therapy; D042241:Early Diagnosis; D015180:Electrophoresis, Gel, Two-Dimensional; D019204:GTP-Binding Proteins / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology; D008969:Molecular Sequence Data; D009062:Mouth Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000628:therapy; D009363:Neoplasm Proteins / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D040901:Proteomics / Q000379:methods*; D034622:RNA Interference; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; C419368:RACK1 protein, human; D012333:RNA, Messenger; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D019204:GTP-Binding Proteins