S100A8 Is Identified as a Biomarker of HPV18-Infected Oral Squamous Cell Carcinomas by Suppression Subtraction Hybridization, Clinical Proteomics Analysis, and Immunohistochemistry Staining

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• 作者：Wan-Yu Lo ; Chien-Chen Lai ; Chun-Hung Hua ; Ming-Hsui Tsai ; Shiuan-Yi Huang ; Chang-Hai Tsai ; Fuu-Jen Tsai
• 刊名：Journal of Proteome Research
• 出版年：2007
• 出版时间：June 2007
• 年：2007
• 卷：6
• 期：6
• 页码：2143 - 2151
• 全文大小：953K
• 年卷期：v.6,no.6(June 2007)
• ISSN：1535-3907

文摘

The purpose of this work is to differentiate between the Human papillomaviruses 18 positive (HPV18+)and negative (HPV18-) oral squamous cell carcinomas (OSCC) in oral cancer patients with cancer-associated oral habits (betel quid chewing, cigarette smoking, and alcohol drinking). Both gene andprotein expression profiles of HPV18+ and HPV18- OSCC were compared: we then further exploredthe biological effect of HPV in oral cancer. Suppression subtraction hybridization (SSH), clinicalproteomics analysis, and immunohistochemistry (IHC) staining were carried out in the HPV18+ andHPV18- OSCC groups. HPV typing detection revealed that 11 OSCC tissues from 82 patients werepositive for HPV18. The SSH experiment showed that 4 cancer-associated genes were highly transcribedwithin 11 cDNA libraries of HPV18+ OSCC, including poly(ADP-ribose)polymerase I (PARP1), replicationprotein A2 (RPA2), S100A8, and S100A2. Clinical proteomics analysis indicated that there was over10-fold overexpression of Stratifin, F-actin capping protein alpha-1 subunit (CapZ alpha-1), Apolipoprotein A-1 (ApoA-1), Heat-shock protein 27 (HSP27), Arginase-1, p16^INK4A, and S100 calcium-bindingprotein A8 (S100A8) in HPV18+ OSCC. Interestingly, the results from SSH and protemics analysisshowed that S100A8 was overexpressed in HPV18+ OSCC. Moreover, IHC staining demonstrated thatS100A8 was up-regulated in HPV18+ OSCC tissues. Our results suggest that S100A8 plays an importantrole in oral carcinogenesis following HPV18 infection; therefore, S100A8 may be a powerful biomarkerof HPV18 as well as a potential therapeutic target for HPV18+ OSCC patients. The study is the first toidentify S100A8 as a biomarker in HPV-associated cancer. Furthermore, this is also the first study todiscover a biomarker by combining SSH, clinical proteomics, and IHC stain analysis in oral cancer-associated research.