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Yang M.,Nanjing Southeast University | Liu R.,Nanjing Southeast University | Sheng J.,Nanjing Southeast University | Liao J.,Nanjing Southeast University | And 5 more authors.
Oncology Reports | Year: 2013

Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies worldwide. To reduce the high morbidity and mortality of the disease, sensitive and specific biomarkers for early detection are urgently needed. Tumor-specific microRNAs (miRNAs) seem to be potential biomarkers for the early diagnosis and treatment of cancer. In this study, differentially expressed miRNAs in tumor tissues and adjacent non-tumor tissues were detected by miRNA microarrays. Stem-loop real-time reverse transcription PCR was conducted to verify the candidate miRNAs discovered by microarray analysis. The data showed that hsa-miR-338-3p, hsa-miR-218 and hsa-miR-139-5p were downregulated in tumor tissues compared with adjacent non-tumor tissues, while hsa-miR-183, hsa-miR-574-5p, hsa-miR-21* and hsa-miR-601 were upregulated in tumor tissues. Multiple regression analysis revealed the aberrant expression of hsa-miR-338-3p, hsa-miR-139-5p, hsa-miR-574-5p and hsa-miR-601 increased the risk of esophageal cancer. Furthermore, we found hsa-miR-21 was significantly increased in heavy drinking patients. Therefore, there is a set of differentially expressed miRNAs in esophageal cancer which may be associated with the incidence and development of ESCC. Differential expression profiles of miRNAs in ESCC may be promising biomarkers for the early screening of high-risk populations and early detection. Source


Su Y.,Nanjing Southeast University | Yin L.,Nanjing Southeast University | Liu R.,Nanjing Southeast University | Sheng J.Y.,Nanjing Southeast University | And 7 more authors.
Medical Oncology | Year: 2014

To determine the relevance of O-6-methylguanine-DNA methyltransferase (MGMT), human mutS homolog 2 (hMSH2), and human mutL homolog 1 (hMLH1) in TP53 mutations in esophageal squamous cell carcinoma, we employed methylation-sensitive high-resolution melting technology and methylation-specific polymerase chain reaction (PCR) to analyze promoter hypermethylation of MGMT, hMSH2, and hMLH1, respectively, in 51 paired tumors and their adjacent normal tissues. The protein expression of the three proteins was also evaluated by Western blot analysis, and the PCR products of TP53, from exon 5 to exon 8, were directly sequenced to measure the mutation spectrum. Esophageal tumor tissues embraced statistically higher MGMT and hMSH2 promoter methylation level than normal tissue. The promoter methylation status of MGMT and hMSH2 corresponds positively with the protein expression level of MGMT and hMSH2. However, such relevance was not found for hMLH1. Furthermore, TP53 mutation status was well associated with MGMT and hMSH2 promoter methylation status, indicating that silencing of the two genes could lead to TP53 mutation in ESCC. © Springer Science+Business Media New York 2013. Source


Chu H.,Nanjing Medical University | Cao W.,Nanjing Medical University | Chen W.,Nanjing Medical University | Pan S.,Nanjing Medical University | And 7 more authors.
International Journal of Cancer | Year: 2012

Interleukin-23 (IL-23)/IL-23 receptor (IL-23R) is essential for Th17 cell-mediated immune response, involved in autoimmune diseases and cancer pathogenesis. Two potentially functional genetic single nucleotide polymorphisms (SNPs; IL-23R rs6682925 T>C and rs1884444 T>G) were found to contribute to cancer susceptibility. In our study, we conducted a case-control study including 1,645 patients with esophageal cancer and 1,694 cancer-free controls in a Chinese population to assess the association between the two SNPs and the risk of esophageal cancer. We found that IL-23R rs6682925 TC/CC and rs1884444 TG/GG variant genotypes were associated with significantly increased risk of esophageal cancer [rs1884444: adjusted odds ratio (OR) = 1.16, 95% confidence intervals (CIs) =1.01-1.33; rs6682925: adjusted OR = 1.23, 95% CIs = 1.07-1.42], compared to their corresponding wild-type homozygotes. Furthermore, the increased risks associated with the two SNPs were independent from smoking and alcohol drinking status. These findings indicated that genetic variants in IL-23R may contribute to esophageal cancer risk in our Chinese population. Copyright © 2011 UICC. Source


Su Y.,Nanjing Southeast University | Liu R.,Nanjing Southeast University | Sheng J.,Nanjing Southeast University | Liu H.,Nanjing Southeast University | And 8 more authors.
DNA and Cell Biology | Year: 2012

The abnormal function of O6-methylguanine-DNA methyltransferase (MGMT) is reported to be associated with the occurrence of various tumors and malignant tumor progression. However, little evidence is available to describe its role in esophageal carcinogenesis. To address this issue, we constructed a stable MGMT-silenced esophageal cancer cell line by RNA interference, and exposed the cells to N-methyl-N-nitro-N-nitrosoguanidine (MNNG) to investigate the role that MGMT plays in toxicity. During this time, we also observed the malignant behavior of cells in vitro and in vivo. In addition, two-dimensional electrophoresis and mass spectrometry were used to detect and confirm the proteins that were differentially expressed in the MGMT-deficient and MGMT-proficient cells, which might be responsible for the malignant alteration of cells. Results showed that the IC50 of MGMT-deficient and MGMT-proficient cells exposed to MNNG was 30μM and 65μM, respectively, and MGMT-deficient cells had more aggressive motility and invasive abilities compared with MGMT-proficient cells. Nineteen differentially expressed proteins were detected between the MGMT-deficient and MGMT-proficient cells, 14 of which were identified, including the membrane-cytoskeleton linker protein, Ezrin, which was confirmed by both mass spectrometry and western blot analysis. The correlation between MGMT, Ezrin expression, and the malignant behavior of one normal epithelial esophageal cell line and seven esophageal cancer lines is discussed. In conclusion, loss of MGMT expression leads EC109 esophageal cancer cells to have increased malignant behavior, which may correlate with its high Ezrin protein expression. © Copyright 2012, Mary Ann Liebert, Inc. 2012. Source

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