Population-specific genome-wide mapping of expression quantitative trait loci in the colon of Han Chinese.

OBJECTIVE: To establish the colonic expression quantitative trait locus map in Han Chinese population and provide a functional reference for interpreting genetic associations of diseases such as inflammatory bowel disease (IBD). METHODS: Colonic mucosal biopsies and peripheral blood samples were obtained from 48 Chinese Han individuals (24 ulcerative colitis patients and 24 healthy controls). Transcription profiling was performed using human whole genome expression array. Genotyping was done using a population-specific genotype array. Imputation was performed using IMPUTE2. Association between genotypes and gene expression was analyzed using a Matrix Expression Quantitative Trait Loci (eQTL) R package to identify eQTL. We used ChIPpeakAnno R package for annotation of the eQTL. Linkage disequilibrium between the eQTL and IBD risk loci was also investigated. RESULTS: We identified 6 377 single nucleotide polymorphism-transcript interactions (cis-eQTL) in the colon of the Chinese participants. Most of the eQTL located near the transcription starting sites and overlapped with histone modification marks on the genome. A significant proportion of the eQTL were found to be within transcription factor-binding sites. Two IBD risk loci were found to be colon cis-eQTL in Chinese individuals, and 51 cis-eQTL were identified in another 18 IBD risk loci. CONCLUSIONS: This study defined a population-specific catalogue of colon eQTL in the Chinese population. Potential functional variants of IBD association signals were identified. We provided a useful reference dataset for fine mapping IBD risk loci and identifying causal variants in the Chinese Han population.

Increased expression of HSP27 inhibits invasion and metastasis in human esophageal squamous cell carcinoma.

Previous studies have indicated that heat shock protein 27 (HSP27) had high correlation with the development and progression in several tumors. However, the roles of HSP27 in esophageal squamous cell carcinoma (ESCC) were uncertain. The aim in this study is to investigate the potential roles of HSP27 in the metastasis of ESCC. The expression of HSP27 in ESCC tissues and four human esophageal cancer cell lines were examined by immunohistochemistry and Western blotting, respectively. Wound healing assays, transwell assays, and in vivo assays were used to identify the differences of metastasis potential between normal and HSP27 overexpressed cells. HSP27 expression was downregulated in cancer tissue compared to the matched normal tissue. And the positive staining was mainly located in the cytoplasm. Statistical analyses showed that the expression of HSP27 in ESCC was significantly correlated with the tumor differentiation (P = 0.023), the patient's TNM stage (P = 0.013), lymph metastasis (P = 0.020), and distant metastasis (P = 0.017). HSP27 expression was significantly lower in highly metastatic cells than the less ones. The metastatic potentials of EC9706-H and EC109-H cells were higher than EC9706-L and EC109-L cells. In vitro and in vivo assays showed that overexpression of HSP27 in highly metastatic cells dramatically decreased their metastatic capacity. This study indicated that the expression level of HSP27 may be inversely correlated with the metastasis behavior of ESCC, and HSP27 may play an important role in this progression. HSP27 may be a potential molecular target for the therapy and prognosis of patients with ESCC.

Increased expression of FOXQ1 is a prognostic marker for patients with gastric cancer.

Altered expression of forkhead box Q1 (FOXQ1) is observed in various types of human cancers. However, the clinical significance of FOXQ1 expression in gastric cancer (GC) remains largely unknown. The present study aims to explore the clinicopathological significance and prognostic value of FOXQ1 in GC. FOXQ1 messenger RNA (mRNA) and protein expression were determined by quantitative real-time reverse transcriptase-polymerase chain reaction and Western blot in 20 pairs of fresh frozen GC tissues and corresponding noncancerous tissues. Additionally, FOXQ1 expression was analyzed by immunohistochemistry in 158 clinicopathologically characterized GC cases. The correlation of FOXQ1 expression with patients' survival rate was assessed by Kaplan-Meier and Cox regression. Our results showed that the expression levels of FOXQ1 mRNA and protein in GC tissues were both significantly higher than those in non-cancerous tissues. Our results showed that the high expression of FOXQ1 in GC was related to tumor size (P = 0.026), histological grade (P = 0.021), lymph node involvement (P = 0.002), and tumor-node-metastasis stage (P = 0.028). Kaplan-Meier survival analysis showed that a high expression level of FOXQ1 resulted in a significantly poor prognosis of GC patients. Furthermore, Cox multivariates analysis indicated that FOXQ1 expression level was an independent prognostic factor for the overall survival rate of GC patients. In conclusion, overexpression of FOXQ1 is closely related to progression of GC and might be regarded as an independent predictor of poor prognosis for GC.

Diagnosis of atrophic body gastritis in Chinese patients by measuring serum pepsinogen.

OBJECTIVE: Atrophic body gastritis (ABG) is common in China. Although histology via endoscopy is an efficient and reliable means of diagnosing ABG, it is an invasive procedure. Therefore, in the present study serum pepsinogen (PG) was used as a biomarker to develop a novel noninvasive test as the first option for screening of ABG in certain groups of Chinese. METHODS: The study population consisted of 81 selected dyspeptic patients (mean age, 64.8 +/- 0.7 years; M:F, 43:38) who underwent diagnostic gastroscopy. At least four biopsy specimens were taken from the antrum and corpus of the stomach (two specimens from each site) for histological diagnosis. Blood samples for ELISA assays of serum pepsinogen I (PGI), pepsinogen II (PGII) and IgG antibodies against Helicobacter pylori (Hp IgG) were drawn after endoscopy. Cut-off points were calculated using receiver operating curves (ROC). RESULTS: There was no correlation between serum PG and atrophy in the antral mucosa. The mean serum concentration of PGI was lower (P < 0.05) in patients with ABG (89.9 microg/L) than in those with normal mucosa (NM) and non-ABG (123.7 microg/L and 139.1 microg/L). The mean ratio of PGI:PGII was also lower (P < 0.01) in patients with ABG (6.2) than in those with NM and non-ABG (11.6 and 11.7). There was no difference in serum PGI or the PGI:PGII ratio between patients with and without H. pylori infection. For diagnosing ABG, the area under the ROC of PGI and the PGI:PGII ratio was 0.741 (95% CI: 0.627-0.856) and 0.874 (95% CI: 0.788-0.961), respectively. The maximum of the Youden's index (YI) of PGI and the PGI:PGII ratio was 0.426 and 0.722, respectively. The best cut-off point for PGI was 97.1 microg/L with sensitivity of 67% and specificity of 76%, and for PGI:PGII ratio was 8.1 microg/L, with sensitivity of 89% and specificity of 83%. CONCLUSIONS: The serum PGI:PGII ratio appears to be a sensitive and specific assay for corpus atrophy, thus providing a noninvasive and indicative test for diagnosis of atrophic gastritis.