Identification of Novel Candidate Biomarkers for Oral Squamous Cell Carcinoma Based on Whole Gene Expression Profiling

[摘要] This study aimed to determine the whole gene expression profiles and to ascertain potential biomarkers for 22 oral squamous cell carcinoma (OSCC) among Thai patients using the Illumina Human HT-12, V4.0 Expression BeadChip array. Result indicated 2,724 differential expressed genes composed of 1,560 up-regulated and 1,164 down-regulated genes (unpaired t-test, p-value <0.05; fold change ≥2.0 and ≤2.0). The top 9 up-regulated genes were validated in 39 OSCC cases using TaqMan real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assay. Among these, the up-regulation of peptidase inhibitor 3 (PI3) and keratin 17 (KRT17) genes was harbored in all 39 OSCC patients (100%). Likewise, statistical analysis indicated that gene expression in 8 selective genes including keratin 16 (KRT16), keratin 14 (KRT14), keratinocyte differentiation-associated protein (KRTDAP), keratin 6B (KRT6B), PI3, S100 calcium binding protein A7 (S100A7), stratifin (SFN) and keratin 5 (KRT5) was significantly associated with well differentiated OSCC (p-value <0.05). Moreover, high level of KRT17 protein was significantly associated with well differentiated OSCC compared to moderately OSCC (p-value = 0.041). Notably, using nested-PCR analysis indicated all OSCC cases in this study were HPV-free. Especially, KRTDAP, PI3, SFN mRNA expression were first reported among patients with OSCC. Conclusion, the whole transcript expression study and TaqMan real-time qRT-PCR assay were relevant regarding the increase in gene expression in OSCC. In addition, the up-regulation of PI3 and KRT17 might constitute potential candidate molecular biomarkers to diagnose patients with OSCC.

[关键词] Oral squamous cell carcinoma;Gene expression profile;Biomarker;PI3;KRT17