Comprehensive tissue-specific gene set enrichment analysis and transcription factor analysis of breast cancer by integrating 14 gene expression datasets.

Breast cancer is the most commonly diagnosed malignancy in women. Several key genes and pathways have been proven to correlate with breast cancer pathology. This study sought to explore the differences in key transcription factors (TFs), transcriptional regulation networks and dysregulated pathways in different tissues in breast cancer. We employed 14 breast cancer datasets from NCBI-GEO and performed an integrated analysis in three different tissues including breast, blood and saliva. The results showed that there were eight genes (CEBPD, EGR1, EGR2, EGR3, FOS, FOSB, ID1 and NFIL3) down-regulated in breast tissue but up-regulated in blood tissue. Furthermore, we identified several unreported tissue-specific TFs that may contribute to breast cancer, including ATOH8, DMRT2, TBX15 and ZNF367. The dysregulation of these TFs damaged lipid metabolism, development, cell adhesion, proliferation, differentiation and metastasis processes. Among these pathways, the breast tissue showed the most serious impairment and the blood tissue showed a relatively moderate damage, whereas the saliva tissue was almost unaffected. This study could be helpful for future biomarker discovery, drug design, and therapeutic and predictive applications in breast cancers.

[The expression of hTERT and p53 protein in pre-malignant and malignant lesions of human oral mucosa].

PURPOSE: To investigate the roles of hTERT and p53 protein in malignant changes of oral mucosal precancerous lesions and the relations between hTERT and p53. METHODS: The expression of hTERTmRNA and p53 were measured using in situ hybridization and immunohistochemical assay in 9 cases of oral mucosal hyperplasia, 11 cases of light dysplasia, 10 cases of medium dysplasia, 9 cases of carcinomas in situ and 11 cases of squamous cell carcinomas. The results were processed by medical photographic system, and analyzed statistically by one-way ANOVA. The relation to hTERT and p53 was analyzed statistically by Pearson correlations. RESULTS: It was found that from hyperplasia to light dysplasia, medium dysplasia, carcinomas in situ and squamous cell carcinomas, the indexes of positive cell vessels and the value of OD increased, arriving at the apex in squamous cell carcinoma. With phenotypic progression and the degree of dysplasia, hTERT and p53 expression cells extend from basal layer to the keratinous layer. In highly-differentiated squamous cell carcinomas, expression cells were mainly located around the nests. Stained cells dispersed throughout the tumor tissue in low-differentiated squamous cell carcinomas. p53 was undetectable in hyperplasia and light dysplasia, but p53 was observed in 66.67% cases of high dysplasia and 72.72% cases of squamous cell carcinomas. There was not a significant linear correlation between hTERT and p53. CONCLUSIONS: The results suggest that activation of telomerase and p53 play a role in the process of malignant changes of oral mucosal precancerous lesions. Oral squamous cell carcinoma is a disease that has been found in association with many factors.