PDF(Pubmed)
Abstract：
BACKGROUND: Identification of molecular biomarkers in the saliva and serum of oral cavity cancer patients represents a first step in the development of essential and efficient clinical tools for early detection and post-treatment monitoring. We hypothesized that molecular analyses of paired saliva and serum samples from an individual would likely yield better results than analyses of either serum or saliva alone.
METHODS: We performed whole-transcriptome and small non-coding RNA sequencing analyses on 32 samples of saliva and serum collected from the same patients with oral squamous cell carcinoma (OSCC) and healthy controls (HC).
RESULTS: We identified 12 novel saliva and serum miRNAs and a panel of unique miRNA and mRNA signatures, significantly differentially expressed in OSCC patients relative to HC (log2 fold change: 2.6-26.8; DE: 0.02-0.000001). We utilized a combined panel of the 10 top-deregulated miRNAs and mRNAs and evaluated their putative diagnostic potential (>87% sensitivity; 100% specificity), recommending seven of them for further validation. We also identified unique saliva and serum miRNAs associated with OSCC and smoking history (OSCC smokers vs. never-smokers or HC: log2 fold change: 22-23; DE: 0.00003-0.000000001). Functional and pathway analyses indicated interactions between the discovered OSCC-related non-invasive miRNAs and mRNAs and their targets, through PI3K/AKT/mTOR signaling.
CONCLUSIONS: Our data support our hypothesis that using paired saliva and serum from the same individuals and deep sequencing analyses can provide unique combined mRNA and miRNA signatures associated with canonical pathways that may have a diagnostic advantage relative to saliva or serum alone and may be useful for clinical testing. We believe this data will contribute to effective preventive care by post-treatment monitoring of patients, as well as suggesting potential targets for therapeutic approaches.
METHODS: We performed whole-transcriptome and small non-coding RNA sequencing analyses on 32 samples of saliva and serum collected from the same patients with oral squamous cell carcinoma (OSCC) and healthy controls (HC).
RESULTS: We identified 12 novel saliva and serum miRNAs and a panel of unique miRNA and mRNA signatures, significantly differentially expressed in OSCC patients relative to HC (log2 fold change: 2.6-26.8; DE: 0.02-0.000001). We utilized a combined panel of the 10 top-deregulated miRNAs and mRNAs and evaluated their putative diagnostic potential (>87% sensitivity; 100% specificity), recommending seven of them for further validation. We also identified unique saliva and serum miRNAs associated with OSCC and smoking history (OSCC smokers vs. never-smokers or HC: log2 fold change: 22-23; DE: 0.00003-0.000000001). Functional and pathway analyses indicated interactions between the discovered OSCC-related non-invasive miRNAs and mRNAs and their targets, through PI3K/AKT/mTOR signaling.
CONCLUSIONS: Our data support our hypothesis that using paired saliva and serum from the same individuals and deep sequencing analyses can provide unique combined mRNA and miRNA signatures associated with canonical pathways that may have a diagnostic advantage relative to saliva or serum alone and may be useful for clinical testing. We believe this data will contribute to effective preventive care by post-treatment monitoring of patients, as well as suggesting potential targets for therapeutic approaches.
摘要：
背景：确定口腔癌患者唾液和血清中的分子生物标记代表了开发用于早期检测和治疗后监测的基本和有效临床工具的第一步。我们假设来自个体的配对唾液和血清样品的分子分析可能比单独的血清或唾液分析产生更好的结果。
方法：我们对从口腔鳞状细胞癌（OSCC）和健康对照（HC）患者收集的32份唾液和血清样本进行了全转录组和小型非编码RNA测序分析。
结果：我们鉴定了12个新的唾液和血清miRNAs以及一组独特的miRNA和mRNA标记，在OSCC患者中相对于HC显著差异表达(log2倍数变化:2.6-26.8;DE:0.02-0.000001)。我们使用了10个最高失调的miRNAs和mRNAs的组合组，并评估了它们的推定诊断潜力（>87％的灵敏度；100％的特异性）。建议其中七个进行进一步验证。我们还鉴定了与OSCC和吸烟史相关的独特唾液和血清miRNA（OSCC吸烟者与从不吸烟者或HC：log2倍变化：22-23；DE：0.00003-0.000000001）。功能和通路分析显示发现的OSCC相关的非侵入性miRNAs和mRNAs与其靶标之间的相互作用。通过PI3K/AKT/mTOR信号。
结论：我们的数据支持我们的假设，即使用来自同一个体的配对唾液和血清以及深度测序分析可以提供与经典途径相关的独特的mRNA和miRNA组合特征，相对于单独的唾液或血清可能具有诊断优势，并且可能对临床试验有用。我们相信这些数据将有助于通过对患者的治疗后监测来进行有效的预防护理，以及建议治疗方法的潜在目标。
方法：我们对从口腔鳞状细胞癌（OSCC）和健康对照（HC）患者收集的32份唾液和血清样本进行了全转录组和小型非编码RNA测序分析。
结果：我们鉴定了12个新的唾液和血清miRNAs以及一组独特的miRNA和mRNA标记，在OSCC患者中相对于HC显著差异表达(log2倍数变化:2.6-26.8;DE:0.02-0.000001)。我们使用了10个最高失调的miRNAs和mRNAs的组合组，并评估了它们的推定诊断潜力（>87％的灵敏度；100％的特异性）。建议其中七个进行进一步验证。我们还鉴定了与OSCC和吸烟史相关的独特唾液和血清miRNA（OSCC吸烟者与从不吸烟者或HC：log2倍变化：22-23；DE：0.00003-0.000000001）。功能和通路分析显示发现的OSCC相关的非侵入性miRNAs和mRNAs与其靶标之间的相互作用。通过PI3K/AKT/mTOR信号。
结论：我们的数据支持我们的假设，即使用来自同一个体的配对唾液和血清以及深度测序分析可以提供与经典途径相关的独特的mRNA和miRNA组合特征，相对于单独的唾液或血清可能具有诊断优势，并且可能对临床试验有用。我们相信这些数据将有助于通过对患者的治疗后监测来进行有效的预防护理，以及建议治疗方法的潜在目标。
