Hierarchal gene master regulators of one case of papillary thyroid cancer. Homo sapiens

The incidence of thyroid cancer (TC) has doubled in recent years but the molecular mechanisms responsible for various TC forms are largely unknown. We hypothesize that, in a thyroid tumor, cancer nodules and surrounding benign tissue are governed by different gene master regulators (GMRs). GMRs are defined as coding/non-coding RNAs whose strongly protected (by the homeostatic mechanisms) abundance modulates most functional pathways by coordinating the expression of their composing genes. GMRs are the most legitimate targets for TC gene therapy. However, because of strong expression control, GMRs are not selectable among TC biomarkers whose frequent regulation in large cancer patient populations indicates low protection as for minor players. We tested the hypothesis by profiling the transcriptomes of the papillary cancer and benign tissue from a surgically removed TC. The hierarchy of the known biomarkers was established for both cancer and benign regions of the tumor based on their gene commanding height (GCH), an original measure combining the expression control and coordination with expression of other genes. We found that 1/3 of the 544 known biomarkers had higher GCH in the malignant region, 1/3 in the benign region, while the rest did not discriminate between the two, raising the question of the biomarkers’ utility. Overall design: Two-conditions (N=normal/benign region of the tumor, T=papllary thyroid cancer region of the tumor), 4 replicas of each condition