ABSTRACT
Previous studies have suggested that an association exists between the proline dehydrogenase gene (PRODH) and increased schizophrenia risk. We examined the prevalence of the PRODH 757C/T (Arg185Trp), 1766A/G (Gly521Arg), and 1852G/A (intronic mutation) polymorphisms in 175 patients with schizophrenia and 185 control subjects. All subjects were of Iranian ancestry. The PRODH 757TT, 1852AA, and 1766GG genotypes were associated with an increased risk of schizophrenia (odds ratio = 1.38, 95% confidence interval: 0.88-2.16, P = 0.001, P = 0.001, respectively). The activity alleles in the PRODH genotype combinations were associated with an increased risk of schizophrenia (haplotype analysis, TAG genotype P = 0.007). Our findings support a major role for the PRODH 757TT, 1766GG, and 1852AA genotypes alone and in combination for schizophrenia susceptibility.
Subject(s)
Alleles , Polymorphism, Single Nucleotide , Proline Oxidase/genetics , Schizophrenia/genetics , Adolescent , Adult , Age Factors , Case-Control Studies , Educational Status , Female , Gene Expression , Gene Frequency , Genetic Predisposition to Disease , Haplotypes , Humans , Introns , Male , Middle Aged , Odds Ratio , Risk , Schizophrenia/physiopathologyABSTRACT
Human cancer cells resemble stem cells in expression signatures leading them to share some features, most notably, self-renewal. A complex network of transcription factors and signaling molecules are required for continuation of this trait. ZNF797 (SALL4) is a zinc finger transcriptional activator crucial for maintenance of self-renewal in stem cells; however, its expression level has not yet been elucidated in gastric tumor cells. Its expression was analyzed to determine this level and probable clinicopathological consequences. SALL4 expression in fresh tumor and distant tumor-free tissues from 46 colorectal samples was compared by real-time polymerase chain reaction. Greater than a 2-fold increase in SALL4 expression was detected in 89.5% of tumors vs normal related tissues. SALL4 expression was significantly correlated with tumor cell metastasis to lymph nodes, especially in moderately differentiated tumor samples (P < 0.05). Furthermore, higher levels of SALL4 mRNA expression were significantly associated with younger patients with tumor cells in stages I and II (P < 0.05). These results indicate a relationship between SALL4 expression and tumor cell metastasis to lymph nodes and consequent progression of tumors to advanced stages III and IV. Along with the promising evidence of its role in self-renewal in various cancers, SALL4 is introduced as a potentially interesting therapeutic target to reverse a number of aberrations that promote gastric tumor development and maintenance. This result may lead to new approaches for cancer therapy.
ABSTRACT
Gastric cancer remains the third most common cancer in the world. Metastatic disease is a major cause of death in about half of the patients; therefore, early diagnosis is crucial for successful outcome. This study applied a sensitive method for the detection of circulating tumor cells using specific tumor markers for early detection. A total of 80 blood samples from 40 patients and 40 age-matched healthy controls were collected for the study. Circulating mRNA levels of two tumor markers, tumor endothelial marker 8 (TEM-8) and carcinoembryogenic antigen (CEA) were evaluated using absolute quantitative real-time PCR assay in the Stratagene Mx-3000P real-time PCR system. GAPDH was used to normalize the data. TEM-8 and CEA were detected in patients' blood more than in controls, 22/40 vs 9/40, P=0.005, and 30/40 vs 11/40, P=0.008, respectively. The mRNA level of these markers in patients was significantly higher in comparison to normal controls (P=0.018, 0.01). This panel showed an overall sensitivity of 64% and specificity of 73%. Statistical analysis for demographic variants did not show any significant differences. Both markers were detected more frequently and in significantly higher levels in blood samples of patients compared to samples from normal individuals. Copy number of CEA and TEM-8 mRNA, as detected by real-time quantitative PCR, appears to be a promising marker to evaluate the risk of tumor spread.
