| Objective: A new gene,metastasis-associated in colon cancer-1(MACC1)was discovered in colorectal cancer by whole genome sequencing in 2009.After that,the expression of MACC1 protein was significantly increased in many solid tumor tissues which was closely connected with tumor invasion,metastasis and deterioration.Recently,a series of studies have confirmed that the level of MACC1 in serum or tissue had has a diagnostic and prognostic value for malignant tumors.The present study showed that the single nucleotide polymorphism(SNP)of MACC1 gene was associated with metastasis,survival rate and risk of occurrence of colorectal cancer,breast cancer,hepatocellular carcinoma.The aim of our research was to discover the prognostic and diagnostic value of serum MACC1 levels in gastric cancer patients.The purpose of this study is to investigate the relationships among the diagnostic and prognostic value of serum MACC1 protein level and its lymphatic metastasis,distant metastasis and pathological staging of gastric cancer.At the same time,three polymorphisms of MACC1 gene(rs4721888,rs975263,rs1990172)were detected by micro sequencing technology(also called the SNaPshot technology)to analyze the distribution of genotypes and alleles and its relationship with the genetic risk of gastric cancer in our study population.Our study provides a new theoretical basis for the diagnosis,prognosis and molecular genetic mechanism of gastric cancer,and lays a foundation for further research in the future.Method: In our study,the level of MACC1 in serum was measured by enzyme-linked immunosorbent assay(ELISA)in 147 gastric cancer patients(115 for male,32 for female)and 102 healthy volunteers(65 for male,37 for female).Comparisons of serum MACC1 protein levels between cancer group and control group,between male and female in cancer group,different pathological stages were carried out to detect the role of serum MACC1 protein in the diagnosis and prognosis of gastric cancer.We detected the three genotyped SNPs(rs975263,rs1990172,rs4721888)of MACC1 in 147(113 for male,34 for female)gastric patients and 122(81 for male 41 for female)healthy individuals.The results of SNaPshot method were validated by one-generation sequencing.Hardy-Weinberg equilibrium(HWE)was used to test the reliability of population representativeness and comparability in the control group.After adjusting for confounding factors such as sex and age,logistic regression analysis was used to analyze odds ratio(OR)and 95% confidence interval(CI).Finally,we analyzed the relationship between polymorphism of three SNP of MACC1 and genetic susceptibility of gastric cancer in Guangxi population.Results:1.The serum levels of MACC1 protein in cancer group and control group were 273.71(+204.28)(pg/ml)and 171.50(+135.96)(pg/ml)respectively.The serum MACC1 level in the cancer group was significantly higher than control group(P=0.000,P<0.05).The data of serum MACC1 protein in cancer group and control group were analyzed by ROC curve(AUC=0.748,95%CI= 0.689-0.801).When Cut-off was 228.67 pg/ml,the sensitivity and specificity were 63.27% and 74.51% respectively.2.Comparison of serum MACC1 protein between different TNM stages in the gastric cancer(P =0.000,P <0.05).the stage of ? + ? compared with stage ? and ?(P = 0.000,P < 0.05),stage ? + ? to ?(P = 0.020,P < 0.05),stage ? + ? to ?(P = 0.000,P < 0.05),and stage ? to ?(P = 0.000,P < 0.05).3.The levels of serum MACC1 protein in gastric cancer patients also showing statistical differences between different degrees of the invasions(P =0.004,P <0.05),the levels of serum MACC1 protein in the stage T3+T4 is higher than the stage T0+T1+T2(P =0.002,P <0.05).4.The levels of serum MACC1 protein was increased in the lymphatic metastasis group than theose non-lymphatic metastasis group(Z=-3.597,P =0.000,P <0.05).5.There also shows significantly differences about serum MACC1 protein in distant metastasis with those no metastasis(Z=-5.537,P =0.000,P <0.05).6.The level of serum MACC1 had no significantly change by the male and female in the cancer group(Z=-0.420,P=0.674,P >0.05),We also found that it was no obvious correlation with gastric cancer age(r=-0.039,P=0.642,P>0.05).7.The frequencies of different genotypes and alleles at three SNP of MACC1 gene rs975263,rs4721888 and rs1990172 had no statistically significant change in the cancer group when compared with control group.8.There was no difference in age-related analysis between different genotypes in three SNPs.9.The dominant and recessive models constructed at the three SNPs were not related to the genetic susceptibility risk of gastric cancer.10.There was no linkage disequilibrium among MACC1 gene at the three SNPs,and it was not associated with the genetic susceptibility risk of gastric cancer.11.Logistic regression analysis had found that the AG genotype of rs975263 was significantly different from the AA genotype in control group(P=0.017,OR=2.852,95% CI=1.210-6.721).Heterozygous mutant AG genotype may increase the risk of gastric cancer.The AC genotype of rs1990172 was compared with the control CC genotype(P=0.036,OR=0.383,95%CI=0.156~0.940),which indicated that heterozygous mutant AC genotype may reduce risk of gastric cancer.Conclusion:1.The level of serum MACC1 protein was significantly increased in the cancer group compared with the control group.And Serum MACC1 protein was associated with TNM stage,tumor invasion depth,lymphatic metastasis and distant metastasis.The level of serum MACC1 protein has increased in stage ? and ? than stage? + ?,the ivasion stage T3+T4 than T0+T1+T2,and lymphatic metastasis than without lymphatic metastasis,distant metastatic than those without distant metastatic.Serum MACC1 protein may be a sensitivity marker of invasion and metastasis of gastric cancer.2.When the cut-off value was 228.67pg/ml,the sensitivity and specificity were 63.27% and 74.51% respectively,which had certain clinical diagnostic value for gastric cancer.Our findings illustrated that serum MACC1 could serve as a credible diagnostic and prognostic tumor marker for gastric cancer.3.The AG genotype of rs975263 and AC genotype of rs1990172 were related to the genetic susceptibility of gastric cancer which increased the risk of gastric cancer.But the latter genotype may reduce the risk of gastric cancer.4.There was no linkage disequilibrium among MACC1 gene rs975263,rs4721888 and rs1990172 with genetic susceptibility to gastric cancer.5.The different genotypes and alleles at three SNP of MACC1 gene rs975263,rs4721888 and rs1990172 had no statistically significant change with the levels of serum MACC1 protein in gastric cancer patients. |
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