Gene expression profiling analysis contributes to understanding the association between non-syndromic cleft lip and palate, and cancer

Abstract

The present study aimed to investigate the molecular mechanisms underlying non-syndromic cleft lip, with or without cleft palate (NSCL/P), and the association between this disease and cancer. The GSE42589 data set was downloaded from the Gene Expression Omnibus database, and contained seven dental pulp stem cell samples from children with NSCL/P in the exfoliation period, and six controls. Differentially expressed genes (DEGs) were screened using the RankProd method, and their potential functions were revealed by pathway enrichment analysis and construction of a pathway interaction network. Subsequently, cancer genes were obtained from six cancer databases, and the cancer-associated protein-protein interaction network for the DEGs was visualized using Cytoscape. In total, 452 upregulated and 1,288 downregulated DEGs were screened. The upregulated DEGs were significantly enriched in the arachidonic acid metabolism pathway, including PTGDS, CYP4F2 and PLA2G16; and transforming growth factor (TGF)-β signaling pathway, including SMAD3 and TGFB2. The downregulated DEGs were distinctly involved in the pathways of DNA replication, including MCM2 and POLA1; cell cycle, including CDK1 and STAG1; and viral carcinogenesis, including PIK3CA and HIST1H2BF. Furthermore, the pathways of cell cycle and viral carcinogenesis, with higher degrees of interaction were found to interact with other pathways, including DNA replication, transcriptional misregulation in cancer, and the TGF-β signaling pathway. Additionally, TP53, CDK1, SMAD3, PIK3R1 and CASP3, with higher degrees, interacted with the cancer genes. In conclusion, the DEGs for NSCL/P were implicated predominantly in the TGF-β signaling pathway, the cell cycle and in viral carcinogenesis. The TP53, CDK1, SMAD3, PIK3R1 and CASP3 genes were found to be associated, not only with NSCL/P, but also with cancer. These results may contribute to a better understanding of the molecular mechanisms of NSCL/P.

Analysis of dermal fibroblasts isolated from neonatal and child cleft lip and adult skin: Developmental implications on reconstructive surgery

“…The expression profiles of NCFs and OCCFs are practically identical and it must be noted that they differ from normal fibroblasts due to the high incidence of SMA-positive fibroblasts/myofibroblasts, typical of wound healing and stromal cancer-associated fibroblasts ( 27 ). Similar profiles of cleft palate and cancer have also been observed by others ( 54 ). Cancer-associated fibroblasts produce IL-6 and IL-8, which influence differentiation patterns of human keratinocytes to elements with low differentiation status ( 38 ).…”

Validation of Gene Profiles for Analysis of Regional Lymphatic Metastases in Head and Neck Squamous Cell Carcinoma

“…TGF-β1 encodes a secreted ligand of the transforming growth factor-beta superfamily proteins (Kudinov et al, 2016). The band of these ligands and various TGF-β receptors result in the recruitment and stimulation of SMAD3 that promotes the process of carcinogenesis (Chaturvedi et al, 2014;Wang et al, 2016). IFN-α, IFN-β and TGF-β play important roles in regulating the activity of lymph node stromal cells embracing lymphatic endothelial cells (LECs), follicular dendritic cells (DCs), and fibroblastic reticular cells (FRCs) (Yang et al, 2014;Ji, 2016).…”

Systems genetics of nonsyndromic orofacial clefting provides insights into its complex aetiology

“…The RRA method uses a probabilistic model for aggregation that is robust to noise and also facilitates the calculation of significance probabilities for all the genes in the final ranking. Given that based on conventional statistical analyses in DEG identification, a large number of genes (sometimes in thousands) show significant expression change [31], we limited the DEGs to the top 500 as a conservative measure. This set was then filtered based on expression fold-change, calculated as 2^(mean expression value in disease state/mean expression value in control state), and only those that satisfied a fold-change cut-off of 1.7 were retained.…”