ABSTRACT
Objective: To detect the methylation levels of homeobox protein Hox A7 (HOXA7) gene promoter in the plasma of non-small cell lung cancer (NSCLC) and to study the value of HOXA7 methylation and serum levels of the tumor markers carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), and cytokeratin 19 fragment (Cyfra21-1) in the auxiliary diagnosis of NSCLC. Methods: Plasma samples were collected from 80 patients with NSCLC and 50 healthy controls, which were enrolled in Henan Cancer Hospital from January 2012 to December 2016. The plasma HOXA7 methylation levels were detected by real-time quantitative methylation-specific PCR, and the plasma levels of CEA, CA199, and Cyfra21-1 were detected by electrochemical luminescence. The ROC curve was constructed to analyze the clinical value of each index in the differential diagnosis of NSCLC, and the relationship between HOXA7 methylation, clinical parameters, and tumor markers was analyzed. Results: The serum levels of HOXA7 methylation in NSCLC patients were significantly higher (χ2=36.972, P<0.000 1) than the healthy control group. The sensitivity and specificity of HOXA7 methylation in the diagnosis of NSCLC were 68.8% (55/80) and 86.0% (43/50), respectively. Plasma HOXA7 methylation was not related to gender, age, smoking history, or pathological type (all P>0.05), but was related to TNM stage (P<0.05). The plasma HOXA7 methylation level of stageⅣpatients (81.8%, 18/22) was the highest. Cyfra21-1 had the highest value in the diagnosis of NSCLC among tumor markers with a sensitivity of 70.00% and a specificity of 90.00%. The combination of HOXA7 methylation with all three tumor markers had the highest efficiency (AUC=0.893, sensitivity 73.75%, specificity 94%) in the diagnosis of NSCLC. The correlation coefficient between HOXA7 methylation and Cyfra21-1 was the highest (r=0.564, P<0.05). Conclusions: HOXA7 gene methylation is related to the degree of metastasis of NSCLC and proves as an efficient diagnostic marker for NSCLC when combined with tumor marker detection.
ABSTRACT
As a member of homeobox gene family,HOXA7 is a main gene to control hematopoietie cell proliferation and differentiation.The expression and function of HOXA7 in leukemia ale regulated by many upstream elements.and affected by synergism molecules and other homeobox genes. It can induce leukemia through acting on downstream target genes.HOXA7 affects the clinical manifestation of leukemia and overexpression is closely associated with poor therapeutic reaction and prognosis.
ABSTRACT
Objective To investigate the expression and methylation status of HOXA7 gene in human pancreatic cancer cell lines, and to explore the relationship between them.Methods HOXA7 mRNA expression of human pancreatic cancer cell lines BxPC3, CFPAC1, PANC1 and SW1990was detected by RT PCR.Bisulfite sequencing PCR (BSP) and combined bisulfite restriction analysis (COBRA) was used to test promoter methylation status.All the cell lines were treated by 5-aza-2-deoxycytidine (5-aza-dC), and HOXA7mRNA expression, methylation status was detected before and after this treatment.Results HOXA7 mRNA was expressed in BxPC3, CFPAC1 and SW1990, while there was no expression of HOXA7 mRNA in PANC1.HOXA7 promoter methylation rates of CFPAC1, BxPC3, PANC1 and SW1990 were 93.16%, 90.65%,90.09% ,52.30%.HOXA7 promoter methylation rate of SW1990 was significantly lower than those in other 3cell lines ( P ＜0.01 ).After 5-aza-dC treatment, HOXA7 mRNA of PANC1 was expressed again, and HOXA7mRNA of BxPC3 was increasingly expressed;while the expression of HOXA7 mRNA in CFPAC1 and SW1990was not significantly changed after 5-aza-dC treatment.Conclusions The expression of HOXA7 mRNA in BxPC3 and PANC1 was closely correlated with promoter hypermethylation, while there was no obvious relation in CFPAC 1 and SW1990.
ABSTRACT
Homeobex gene,derived firstly from Drosophila, has the ability of regulating normal embry-onic development and proliferation and differentiation of adult tissue cells. Recent studies demonstrate that HOXA7 can be high and low expressed in adult tumor tissues by means of genetic fusion and genetic silencing to regulate genesis and development of tumor cells. To study its expression and regulation in tumor will be helpful for tumor diagnosis ,treatment and prognosis.