Hypermethylation leading to the loss of hypermethylated in cancer-1 (HIC1) gene expression occurs in many different types of human cancer. HIC1 is a transcriptional repressor that directly binds to the promoter region of NAD-dependent deacetylase sirtuin-1 (SIRT1). SIRT1 functions in cell growth, is anti-apoptotic, protect neurons, functions in senescence, and regulates energy restriction. Epigenetic modification and dysregulation affecting the HIC1/SIRT1 axis is potentially important for the development of malignancies. However, the importance of HIC1 expression in the development of papillary thyroid carcinoma, especially in Chinese patients, is uncertain. Therefore, we assessed the level of methylation in the HIC1 promoter and the mRNA and protein expression levels of HIC1 and SIRT1 in human thyroid papillary carcinoma and tumor adjacent control tissues. The demethylation reagent 5-aza-2′-deoxyctidine (5-aza-dc) and an HIC1 overexpression plasmid were used to manipulate the HIC1/SIRT1 pathway, and the effects on cell senescence, apoptosis, and cell cycle progression were assessed. Compared to normal thyroid tissue, thyroid tumors had lower expression of HIC1 and higher SIRT1 expression. The level of HIC1 methylation was also higher in thyroid carcinoma tissues than adjacent tissues. HIC1 expression was closely correlated with patient age and tumor progression. Restoration of HIC1 expression through an overexpression plasmid or 5-aza-dC treatment reduced SIRT1 expression and cell proliferation, and led to senescence, cell cycle arrest, and apoptosis. Aberrant expression of HIC1/SIRT1 and hypermethylation of the HIC1 promoter may be critical for the development and progression of papillary thyroid cancer.

Background：Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors in the world, and its mechanism is related to tumor microenvironment. Immune / stromal score can be used to identify differential expressed genes (DEGs) of cancer, but it has not been reported in ESCC.Methods: The expression profile and clinicopathological information of patients with ESCC were downloaded from The Cancer Genome Atlas (TCGA) database. The immune score and stromal score of patients with ESCC were calculated by ESTIMATE algorithm. The relationship between immune / stromal score and clinicopathological characteristics and survival prognosis of patients with ESCC was analyzed. DEGs were identified according to the score, followed by gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) analysis. The DEGs with prognostic value were revealed by overall survival analysis. Protein-protein interaction (PPI) network analysis was performed on these DEGs. Finally, the DEGs were verified by Chinese Cancer Genomic Database-Esophageal Squamous-Cell Carcinoma (CCGD-ESCC) database. Results: Immune and stromal scores were related to the prognosis of patients with ESCC. 223 DEGs were screened according to immune / stromal scores. GO and KEGG analysis showed that the selected DEGs was mainly related to plasma membrne, immune response and inflammatory response. Overall survival analysis showed that 68 genes were associated with prognosis. PPI network analysis showed that the core genes were CD86, LCP2, TLR7, CSF1R, C1QA, IRF8, CTLA4 and so on. A total of 17 genes with prognostic value were verified by CCGD-ESCC database. Conclusions: we screened and verified tumor microenvironment-related genes that have prognostic value and are expected to be used as therapeutic targets for patients with ESCC.