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Abstract：
Publicly available (own) transcriptomic data have been analyzed to quantify the alteration in functional pathways in thyroid cancer, establish the gene hierarchy, identify potential gene targets and predict the effects of their manipulation. The expression data have been generated by profiling one case of papillary thyroid carcinoma (PTC) and genetically manipulated BCPAP (papillary) and 8505C (anaplastic) human thyroid cancer cell lines. The study used the genomic fabric paradigm that considers the transcriptome as a multi-dimensional mathematical object based on the three independent characteristics that can be derived for each gene from the expression data. We found remarkable remodeling of the thyroid hormone synthesis, cell cycle, oxidative phosphorylation and apoptosis pathways. Serine peptidase inhibitor, Kunitz type, 2 (SPINT2) was identified as the Gene Master Regulator of the investigated PTC. The substantial increase in the expression synergism of SPINT2 with apoptosis genes in the cancer nodule with respect to the surrounding normal tissue (NOR) suggests that SPINT2 experimental overexpression may force the PTC cells into apoptosis with a negligible effect on the NOR cells. The predictive value of the expression coordination for the expression regulation was validated with data from 8505C and BCPAP cell lines before and after lentiviral transfection with DDX19B.
摘要：
已对公开的（自己的）转录组数据进行了分析，以量化甲状腺癌中功能通路的改变，建立基因层次结构，识别潜在的基因靶标并预测其操作效果。表达数据是通过对一例乳头状甲状腺癌（PTC）和遗传操作的BCPAP（乳头状）和8505C（间变性）人甲状腺癌细胞系进行分析而产生的。该研究使用了基因组结构范式，该范式基于可以从表达数据中得出每个基因的三个独立特征，将转录组视为多维数学对象。我们发现甲状腺激素合成的显著重塑，细胞周期,氧化磷酸化和凋亡途径。丝氨酸肽酶抑制剂，Kunitz型,2(SPINT2)被鉴定为所研究的PTC的基因主调节剂。相对于周围正常组织（NOR），癌结节中SPINT2与凋亡基因的表达协同作用显着增加，表明SPINT2实验性过表达可能会迫使PTC细胞凋亡，对NOR细胞的影响可忽略不计。在用DDX19B慢病毒转染之前和之后,用来自8505C和BCPAP细胞系的数据验证表达调节的表达协调的预测值。
