Systemic disease-induced salivary biomarker profiles in mouse models of melanoma and non-small cell lung cancer.
Systemic disease-induced salivary biomarker profiles in mouse models of melanoma and non-small cell lung cancer.
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DOI：
10.1371/journal.pone.0005875
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发表时间：
2009-06-11
期刊：
影响因子：
3.7
通讯作者：
Wong DT
中科院分区：
文献类型：
--
作者：
Gao K;Zhou H;Zhang L;Lee JW;Zhou Q;Hu S;Wolinsky LE;Farrell J;Eibl G;Wong DT
唾液(口服液)是一种新兴的生物流体，可用于临床疾病的检测。虽然口腔疾病(如口腔癌)应用的原理是直观的，但系统性疾病和唾液生物标志物之间的原理和关系尚不清楚。在这项研究中，我们使用了黑色素瘤和非小细胞肺癌的小鼠模型，并比较了荷瘤小鼠和对照组小鼠的转录组生物标志物谱。微阵列分析显示，与对照组相比，荷瘤小鼠的唾液转录本发生了显著变化。小鼠肿瘤、血清、唾液腺和唾液的转录本之间的显著重叠表明唾液生物标记物具有多个来源。此外，我们发现两组显著改变的转录因子(TF)RUNX1、MLXIPL、Trim30和Egr1、Tbx1、Nr1d1在黑色素瘤荷瘤小鼠唾液腺组织中的表达可能分别导致黑色素瘤荷瘤小鼠唾液中82.6%的上调基因表达和62.5%的下调基因表达。我们还发现，在黑色素瘤组织中异位产生神经生长因子(NGF)作为肿瘤释放的介质，可以诱导唾液腺表达Tf Egr-1。综上所述，我们的数据支持这一结论，即随着系统性疾病的发展，唾液生物标记物的分布可能会发生重大变化。虽然疾病诱发唾液生物标志物的起源可能是全身和局部的，但远处肿瘤释放的介质对唾液腺的刺激在调节唾液替代生物标志物方面起着重要作用。
Saliva (oral fluids) is an emerging biofluid poised for detection of clinical diseases. Although the rationale for oral diseases applications (e.g. oral cancer) is intuitive, the rationale and relationship between systemic diseases and saliva biomarkers are unclear. In this study, we used mouse models of melanoma and non-small cell lung cancer and compared the transcriptome biomarker profiles of tumor-bearing mice to those of control mice. Microarray analysis showed that salivary transcriptomes were significantly altered in tumor-bearing mice vs. controls. Significant overlapping among transcriptomes of mouse tumors, serum, salivary glands and saliva suggests that salivary biomarkers have multiple origins. Furthermore, we identified that the expression of two groups of significantly altered transcription factors (TFs) Runx1, Mlxipl, Trim30 and Egr1, Tbx1, Nr1d1 in salivary gland tissue of melanoma-bearing mice can potentially be responsible for 82.6% of the up-regulated gene expression and 62.5% of the down-regulated gene expression, respectively, in the saliva of melanoma-bearing mice. We also showed that the ectopic production of nerve growth factor (NGF) in the melanoma tumor tissue as a tumor-released mediator can induce expression of the TF Egr-1 in the salivary gland. Taken together, our data support the conclusion that upon systemic disease development, significant changes can occur in the salivary biomarker profile. Although the origins of the disease-induced salivary biomarkers may be both systemic and local, stimulation of salivary gland by mediators released from remote tumors plays an important role in regulating the salivary surrogate biomarker profiles.
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DOI：
10.1073/pnas.011404098
发表时间：
2001-01-02
影响因子：
11.1
作者：
Li, C;Wong, WH
通讯作者：
Wong, WH
影响因子：
2.2
作者：
De Vicente, JC;Garcia-Suarez, O;Vega, JA
通讯作者：
Vega, JA
影响因子：
11.2
作者：
Gao, Kai;Dai, Derek L.;Li, Gang
通讯作者：
Li, Gang
影响因子：
4.1
作者：
Iles, R. K.
通讯作者：
Iles, R. K.
影响因子：
7.6
作者：
Palanisamy V;Park NJ;Wang J;Wong DT
通讯作者：
Wong DT