Gene master regulators of papillary and anaplastic thyroid cancers

Abstract

We hypothesize that distinct cell phenotypes are governed by different sets of gene master regulators (GMRs) whose strongly protected (by the homeostatic mechanisms) abundance modulates most cell processes by coordinating the expression of numerous genes from the corresponding functional pathways. Gene Commanding Height (GCH), a composite measure of gene expression control and coordination, is introduced to establish the gene hierarchy in each phenotype. If the hypothesis is true, than one can selectively destroy cancer nodules from a heterogeneous tissue by altering the expression of genes whose GCHs are high in cancer but low in normal cell phenotype. Here, we test the hypothesis and show its utility for the thyroid cancer (TC) gene therapy. First, we prove that malignant and cancer free surrounding areas of a surgically removed papillary TC (PTC) tumor are governed by different GMRs. Second, we show that stable transfection of a gene induces larger transcriptomic alterations in the cells where it has higher GCH than in other cells. For this, we profiled the transcriptomes of the papillary BCPAP and anaplastic 8505C TC cell lines before and after stable transfection with NEMP1, DDX19B, PANK2 or UBALD1. The four genes were selected to have similar expression levels but significantly different GCH scores in the two cell lines before transfection. Indeed, each of the four genes triggered larger alterations in the cells where they had larger GCH. Our results prove the feasibility of a personalized gene therapy approach that selectively targets the cancer cells from a tissue.

Oligodendrocytes Remodel the Genomic Fabrics of Functional Pathways in Astrocytes

“…However, experimental alteration of a gene is expected to have transcriptomic consequences in line with its GCH. We confirmed this hypothesis by stably lentiviral transfecting each of two different human thyroid cancer cell lines (papillary BCPAP and anaplastic 850C) with the same gene (DDX19B, NEMP1, PANK2, UBALD1) [50,51]. Interestingly, the top gene (highest GCH) in one condition scores very low in the other.…”

“…The Gene Commanding Height (GCH) score was introduced recently[50,51] to establish the gene hierarchy in each condition. It combines an estimate of the transcription control of that gene with a measure of its expression coordination with each other gene:…”

Integrated bioinformatics analysis of the association between apolipoprotein E expression and patient prognosis in papillary thyroid carcinoma

“…Microarray data. In total, 4 gene expression datasets of PTC [GSE3678 and GSE3467 (19), GSE60542 (20), and GSE97001 (21)] were downloaded from the GEO database. The GSE3678 dataset contained 7 PTC samples and 7 paired adjacent normal thyroid tissues.…”

Development of A Three-Gene Signature Prediction Model for Lymph Node Metastasis in Papillary Thyroid Cancer

“…S2). After excluding seven tumor samples and 2 normal samples in three datasets, a total of 187 tumor samples and 119 normal control samples in eight datasets (GSE33630 [10,11], GSE60542 [12], GSE66783 [13], GSE5364 [14], GSE129562 [15], GSE97001 [16], GSE3467 [17] and GSE27155 [18,19]) were included this research (Table 1). After performing differential analysis on the 8 datasets by the edgeR and robust rank aggregation algorithm, the DEGs between the normal tissues and PTC tissues of each dataset were obtained, with an adjusted P value < 0.05 and |log2FC (fold change) | > 0.1 as the cut-offs.…”