S100A8 is identified as a biomarker of HPV18-infected oral squamous cell carcinomas by suppression subtraction hybridization, clinical proteomics analysis, and immunohistochemistry staining

Wan Yu Lo, Chien Chen Lai, Chun Hung Hua, Ming Hsui Tsai, Shiuan Yi Huang, Chang Hai Tsai, Fuu Jen Tsai*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

45 Scopus citations

Abstract

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 and protein expression profiles of HPV18+ and HPV18- OSCC were compared: we then further explored the biological effect of HPV in oral cancer. Suppression subtraction hybridization (SSH), clinical proteomics analysis, and immunohistochemistry (IHC) staining were carried out in the HPV18+ and HPV18- OSCC groups. HPV typing detection revealed that 11 OSCC tissues from 82 patients were positive for HPV18. The SSH experiment showed that 4 cancer-associated genes were highly transcribed within 11 cDNA libraries of HPV18+ OSCC, including poly(ADP-ribose)polymerase I (PARP1), replication protein A2 (RPA2), S100A8, and S100A2. Clinical proteomics analysis indicated that there was over 10-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, p16INK4A, and S100 calcium-binding protein A8 (S100A8) in HPV18+ OSCC. Interestingly, the results from SSH and protemics analysis showed that S100A8 was overexpressed in HPV18+ OSCC. Moreover, IHC staining demonstrated that S100A8 was up-regulated in HPV18+ OSCC tissues. Our results suggest that S100A8 plays an important role in oral carcinogenesis following HPV18 infection; therefore, S100A8 may be a powerful biomarker of HPV18 as well as a potential therapeutic target for HPV18+ OSCC patients. The study is the first to identify S100A8 as a biomarker in HPV-associated cancer. Furthermore, this is also the first study to discover a biomarker by combining SSH, clinical proteomics, and IHC stain analysis in oral cancer-associated research.

Original languageEnglish
Pages (from-to)2143-2151
Number of pages9
JournalJournal of Proteome Research
Volume6
Issue number6
DOIs
StatePublished - 06 2007
Externally publishedYes

Keywords

  • Human papilomaviruses 18
  • Oral squamous cell carcinomas
  • Proteomics
  • S100 calcium-binding protein A8
  • Suppression subtraction hybridization

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