RESUMO
BACKGROUND: Chromodomain helicase/ATPase DNA binding protein 1-like gene (CHD1L) is involved in malignancies. However, the role of CHD1L in gastric cancer (GC) has not been elucidated. The aim of this study is to explore the clinical role of CHD1L in GC. METHODS: The gene and protein expression levels of CHD1L were detected by quantitative real-time PCR and Western blot analysis in fresh samples of GC and paired adjacent noncancerous tissue (n = 34). We evaluated the CHD1L expression by immunohistochemistry in a large number of GC patients (n = 616) and paired adjacent noncancerous tissues from December 1, 2004 to December 1, 2008. The correlations of CHD1L expression with clinicopathological features and clinical outcome were analyzed. RESULTS: The gene and protein expression levels of CHD1L were higher in fresh samples of GC than in paired adjacent noncancerous tissues as determined by quantitative real-time PCR and Western blot analysis. Immunohistochemical analysis showed that positive expression rates of CHD1L in GC and paired adjacent noncancerous tissues were 58.7 % (361/616) and 7.3 % (45/616), respectively. CHD1L positivity was significantly associated with clinical stage and distant metastasis. GC patients with positive CHD1L expression had shorter overall survival than those with negative CHD1L expression. Multivariate analysis showed that CHD1L was an independent prognostic marker for overall survival [Hazard Ratio (HR) = 5.952, 95 % confidence interval (CI) = 3.194-11.187, P = 0.0043]. CONCLUSION: These results indicated that CHD1L could serve as a prognostic marker for GC.
Assuntos
Biomarcadores Tumorais/análise , DNA Helicases/biossíntese , Proteínas de Ligação a DNA/biossíntese , Neoplasias Gástricas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Western Blotting , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Reação em Cadeia da Polimerase em Tempo Real , Neoplasias Gástricas/mortalidadeRESUMO
OBJECTIVE: von Hippel-Lindau (VHL) disease is a hereditary tumor syndrome predisposed to the development of tumors in a variety of body organs. The major etiopathogenesis of VHL is a mutation of the VHL tumor-suppressor gene on the short arm of chromosome 3 (3p25-26). We report on the clinical and molecular features of four Chinese kindreds with VHL disease. MATERIALS AND METHODS: The VHL gene was screened for mutation using a direct DNA sequencing analysis and a multiplex ligation-dependent probe amplification (MLPA) for 44 volunteers from these four families. Any unaffected person, with germline VHL gene mutation, was required to undergo further examination, surveillance and treatment. RESULTS: The main lesions and the average diagnostic year of the 20 patients were central nervous system hemangioblastoma (60 %, 34.92 years), renal lesion (60 %, 39.08 years), pancreatic lesion (60 %, 37.67 years), adrenal pheochromocytoma (25 %, 37.8 years) and retinal hemangioblastoma (10 %, 25.5 years). Direct sequencing detected nucleotide substitutions or small deletions in three families and MLPA revealed exon 1 deletion in family A. The five asymptomatic patients were initially diagnosed by genetic analysis and verified radiologically or surgically. CONCLUSIONS: The spectrum of clinical manifestation of VHL in the mainland Chinese population is similar to the observation in Western kindreds. Genetic testing, which plays a crucial role in early diagnosis asymptomatic patients, is obviously superior to clinical informations when diagnosing VHL disease. The members of VHL disease family may benefit from pedigree study, genetic testing, periodic follow-up, early diagnosis and prompt treatment.