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Identification of Novel Candidate Biomarkers for Oral Squamous Cell Carcinoma Based on Whole Gene Expression Profiling.
Pathology & Oncology Research ( IF 2.8 ) Pub Date : 2020-05-29 , DOI: 10.1007/s12253-020-00828-w
Sudaporn Kengkarn 1 , Songsak Petmitr 1 , Usa Boonyuen 1 , Onrapak Reamtong 1 , Sopee Poomsawat 2 , Sirima Sanguansin 3
Affiliation  

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.



中文翻译:

基于全基因表达谱鉴定口腔鳞状细胞癌的新型候选生物标志物。

这项研究旨在使用Illumina Human HT-12,V4.0表达BeadChip阵列,确定泰国患者中22种口腔鳞状细胞癌(OSCC)的完整基因表达谱并确定潜在的生物标志物。结果表明,由1,560个上调和1,164个下调的基因组成的2,724个差异表达基因(未配对t检验,p值<0.05;倍数变化≥2.0和≤2.0)。使用TaqMan实时定量逆转录酶聚合酶链反应(qRT-PCR)分析法对39例OSCC病例中的前9个上调基因进行了验证。其中,肽酶抑制剂3(PI3)和角蛋白17(KRT17)基因的上调在所有39例OSCC患者中都有(100%)。同样,统计分析表明,在包括角蛋白16(KRT16),角蛋白14(KRT14),角质形成细胞分化相关蛋白(KRTDAP),角蛋白6B(KRT6B),PI3,S100钙结合蛋白A7(S100A7),stratifin(SFN)和角蛋白5(KRT5)显着相关差异化的OSCC(p值<0.05)。此外,与中度OSCC相比,高水平的KRT17蛋白与高分化OSCC显着相关(p值= 0.041)。值得注意的是,使用巢式PCR分析表明该研究中所有OSCC病例均不含HPV。特别是KRTDAPPI3SFN首先在OSCC患者中报道了mRNA表达。结论,整个转录本表达研究和TaqMan实时qRT-PCR检测与OSCC基因表达的增加有关。此外,PI3KRT17的上调可能构成诊断OSCC患者的潜在候选分子生物标记。

更新日期:2020-05-29
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