A Golgi-specific protein PAQR3 is closely associated with the progression, metastasis and prognosis of human gastric cancers.

BACKGROUND: The aim of this study is to determine whether PAQR3, a protein specifically localized in the Golgi apparatus, is associated with tumor progression, metastasis and survival of human patients with gastric cancer. PATIENTS AND METHODS: PAQR3 expression status was investigated in a large panel of gastric cancer (n = 300) and their corresponding para-cancerous histological normal tissues (PCHNT) at both mRNA and protein levels. The correlation of PAQR3 expression levels with clinical features such as metastasis and prognosis was analyzed. The effect of PAQR3 on the growth and migration of gastric cancer cells was also determined. RESULTS: PAQR3 was frequently down-regulated in gastric cancer samples compared with PCHNT at both mRNA and protein levels (both P < 0.0001). The expression level of PAQR3 was negatively correlated with Helicobacter pylori infection (P < 0.0001), tumor size (P < 0.0001), tumor stage (P < 0.0001), venous and lymphatic invasion (P < 0.0001), distant and nodal metastasis (P < 0.0001), and patient survival (P < 0.0001). Down-regulation of PAQR3 was highly correlated with increased epithelial-mesenchymal transition (EMT) in gastric cancer samples. In addition, PAQR3 overexpression was able to negatively modulate cell proliferation, migration and EMT of gastric cancer cells. CONCLUSION: PAQR3 is markedly down-regulated in human gastric cancers. PAQR3 expression level is closely associated with the progression and metastasis of gastric cancers. PAQR3 is also a new genetic signature that can predict the prognosis of the patients with gastric cancer.

The impact of E-cadherin expression on the prognosis of esophageal cancer: a meta-analysis.

E-cadherin is a 120-KD transmembrane calcium-dependent cell adhesion protein that has been demonstrated drownregulated in a large amount of invasive tumors. However, its effect on the prognosis of esophageal cancer (EC) remains controversial. All the relevant English articles that reported survival data or clinicopathological parameters were enrolled in this meta-analysis. A total of 24 studies, including 2691 cases, were included in this study. Twelve studies containing 1669 cases were enrolled to synthesize with hazard ratio (HR) and its 95% confidence interval (CI). The pooled HR for all 12 studies enrolled in this meta-analysis was 1.33 (95% CI 1.16-1.52; z = 3.99, P = 0.00). When the study measured by enzyme-linked immunosorbent assay is excluded, the pooled HR-evaluated E-cadherin to reduce the expression in EC, and in esophageal squamous cell carcinoma was 1.39 (95% CI 1.22-1.58; z = 5.08, P = 0.00) and 1.38 (95% CI 1.21-1.56; z = 4.87, P = 0.00), respectively. The risk of reduced E-cadherin expression on poor differentiation degree was 1.636 (95% CI 1.33-2.02). The pooled odds ratio of reduced E-cadherin expression on deeper tumor invasion, lymph node metastasis, and higher clinical stage were 2.63 (95% CI 1.75-3.94), 1.77 (95% CI 1.06 -2.97), and 3.39 (95% CI 1.85-6.23). Reduced E-cadherin expression detected by immunohistochemistry could be a valid prognostic marker in patients with EC, especially in patients with esophageal squamous cell carcinoma. Reduced E-cadherin expression is significantly associated with poorer differentiation degree.

Tumor development is associated with decrease of TET gene expression and 5-methylcytosine hydroxylation.

The TET (ten-eleven translocation) family of α-ketoglutarate (α-KG)-dependent dioxygenases catalyzes the sequential oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine and 5-carboxylcytosine, leading to eventual DNA demethylation. The TET2 gene is a bona fide tumor suppressor frequently mutated in leukemia, and TET enzyme activity is inhibited in IDH1/2-mutated tumors by the oncometabolite 2-hydroxyglutarate, an antagonist of α-KG, linking 5mC oxidation to cancer development. We report here that the levels of 5hmC are dramatically reduced in human breast, liver, lung, pancreatic and prostate cancers when compared with the matched surrounding normal tissues. Associated with the 5hmC decrease is the substantial reduction of the expression of all three TET genes, revealing a possible mechanism for the reduced 5hmC in cancer cells. The decrease of 5hmC was also observed during tumor development in different genetically engineered mouse models. Together, our results identify 5hmC as a biomarker whose decrease is broadly and tightly associated with tumor development.

MSH2 promoter hypermethylation in circulating tumor DNA is a valuable predictor of disease-free survival for patients with esophageal squamous cell carcinoma.

BACKGROUND: Tumor-specific alterations of DNA methylation in circulating DNA have been associated with tumor burden and malignant progression. A wealth of information indicating the potential use of DNA methylation in circulating DNA for cancer screening, prognosis and monitoring of the efficacy of anticancer therapies has emerged. In this study, we examined prospectively whether the presence of plasma DNA with tumor characteristics before oesophagectomy is a predictive factor related to disease-free survival (DFS). METHODS: Promoter hypermethylation of MSH2 was analyzed using real-time methylation-specific PCR (real-time MSP) in paired tumor and plasma samples of 209 patients with esophageal squamous cell carcinoma (ESCC). RESULTS: Aberrant MSH2 methylation was found in 101 of 209 ESCC patients. Of these 101 patients, 77 cases exhibited the same alteration in their plasma DNA. No alterations were found in the plasma DNA of the remaining 108 patients. As a control, we screened for aberrant methylation in the plasma DNA of 60 health individuals. No methylation was found in plasma DNA of these control groups. Follow-up analysis indicated significantly lower DFS for patients with high MSH2 methylation compared to those with MSH2 unmethylation after surgery. CONCLUSIONS: It was suggestted that MSH2 methylation in the plasma would be a good predictor of DFS for these ESCC patients before oesophagectomy.

Identification of high-risk human papillomavirus (hrHPV)-associated genes in early stage cervical squamous cell carcinomas.

This retrospective study investigated gene expression in tumour samples from 38 patients with early stage human papillomavirus (HPV)-associated cervical squamous cell carcinoma (CSCC). The patients were divided into two groups based on the presence of viral markers of HPV16 or HPV18 infection. Gene expression profiles of tumour samples and the corresponding normal cervical epithelium were analysed using cDNA microarrays. Several genes showed differential expression between the two groups of HPV-infected CSCC patients, although seven genes showed similar changes in both groups. The four genes encoding cyclin-dependent kinase inhibitor 2A, matrix metallopeptidase 9, laminin γ-1, and epidermal growth factor receptor were up-regulated, and the three genes encoding transforming growth factor ß receptor 1, interleukin-1α and insulin-like growth factor-binding protein 6 were down-regulated, in both HPV16(+) and HPV18(+) CSCC. These proteins are involved in cell proliferation, cell structure and cell attachment, so their expression might be involved in the mechanism of HPV-induced carcino genesis. A clearer understanding of HPV type-specific gene expression might aid diagnosis and treatment.

An animal model of intrinsic dental erosion caused by gastro-oesophageal reflux disease.

OBJECTIVES: To explore the association between dental erosion and gastro-oesophageal reflux disease (GORD), we used an animal model of GORD. MATERIALS AND METHODS: We performed an operation to force gastro-duodenal contents reflux in male Wistar rats, and examined the teeth in the reflux rats at 15 or 30 weeks postoperatively. Dental erosion was evaluated based on a slightly modified index from a previous report. Estimation of pH was employed in the oesophageal and gastric contents. RESULTS: Macroscopically, dental erosion was only detected in the reflux rats. Histopathologically, dentin exposure was detected in three of the seven cases after 30 weeks. Alveolar bone destruction and osteomyelitis were also noted in severe cases. The pH of the oesophageal and stomach contents was 6.93 +/- 0.15 and 3.7 +/- 0.39, respectively. CONCLUSIONS: We confirmed the relationship between dental erosion and GORD. First step of dental erosion caused by GORD is the loss of surface enamel induced by regurgitation of an acidic liquid and acidic gas. Subsequently, further destruction of dental hard tissues and tooth supporting structure is accelerated by mixed juice with gastric and duodenal contents. The reflux animal model is a useful tool to examine the mechanism of dental erosion in GORD.

[Epidemiologic survey of dental fluorosis and caries in school students in Wensu county in Xinjiang].

OBJECTIVE: To assess the relationship between the dental fluorosis and caries,and their prevalence features in school students in Wensu country in Xinjiang. METHODS: The study groups consisted of 1527 Weuer and Han students at the age of 6 to 16. Dental fluorosis and caries disease were assessed strictly by Dean's Classification Standard and WHO "Oral Health Surveys Basic Methods" (the 3rd ed). The concentration of fluorine in water and urine was measured by using selective electrode. RESULTS: The prevalence and index of dental fluorosis in Weuer and Han students were 73.70%, 64.67%, 1.647, 1.303,respectively. The prevalence of dental caries and DMFT were 61.19%, 42.66%, 1.648, 1.023 respectively. The corresponding values were 51.94%, 52.99%, 1.305, 1.449 for students of fluorosis group and non-fluorosis group, respectively. The fluorine degree of water was 2-5mg/L,the average value of fluorine in urine was 3.64 mg/L in Han students, and 5.28 mg/L in Weuer students. CONCLUSION: The prevalence of dental caries didn't decrease, even though the grevalence of fluorosis was high in Weuer country. The prevalence of fluorosis dental caries in Weuer students were significantly higher than those in Han students. It showed no significant different between the group of fluorosis and the group of non-fluorosis in the prevalence of dental caries, perhaps due to the high fluorine intake, poor oral hygiene, and unqualified medical service.

Current status of lung cancer diagnosis and treatment in Shanghai.

The status of diagnosis and treatment of lung cancers discovered during 1 year in the Shanghai population are presented. A total of 940 lung cancers was detected from inhabitants of 35-64 years of age, with a male/female ratio of 1.8:1. Pathology showed 35.7% adenocarcinoma and 35.1% squamous cell carcinoma. There was a predominance of adenocarcinoma (47.6%) in females and of squamous cell carcinoma (44.6%) in males. Most (68.6%) of the lesions detected were already advanced in contrast to 14.7% of Stage I disease. The need for vigilance on the part of doctors was demonstrated by the fact that 23.3% of patients were seen by the doctor within 1 month after presenting with symptoms and 44.5% of them had their diagnosis suspected within 1 month after their first hospital visit. The treatment consisted of surgery for 33.3%, chemotherapy for 35%, traditional Chinese medicine for 20% and symptomatic management for 9.6% of patients. As only 55.8% Stage I patients were treated by surgery, the treatment protocol seemed to be improperly biased. The adequate training of health workers was shown by the fact that 79.7% of these patients were confirmed by pathology and/or cytology and most of the Stage I lesions were diagnosed outside the hospital.