Node metastasis, CA125 expression, tumor size and tumor histology. A statistically significant association with clinical stage was found (P = 0.038). No relationships between the polymorphism and age at diagnosis, degree of tumor differentiation, lymph node metastasis, CA125 expression, tumor size or tumor histology were found. Thus, the MTDH (2470G.A) polymorphism may be an indicator of clinical stage in ovarian cancer.level in vivo. As shown in Fig. 2, the levels of MTDH protein in 15 ovarian cancer tissues were significantly higher than those in 17 normal tissues (P,0.01). As shown in Fig. 2B and 2C, the MTDH protein expression was higher in patients with the GG or GA genotypes than in those with the AA genotype, but these differences were not significant (P.0.05). These findings suggest that the SNP 2470G.A may not significantly impact the expression of the MTDH gene.DiscussionMTDH plays a critical role in tumor biology, and it is involved in a variety of tumor biological behaviors. Our group was the first to discover a significant association between MTDH and tumor susceptibility: that is, that 2 MTDH variants are associated with breast cancer [34]. In this study, we further analyzed various SNPs in MTDH and found another SNP (rs16896059, 2470G.A) with statistically significant differences between ovarian cancer case and control groups. Furthermore, rs16896059 was statistically significantly associated with the clinical stage of the tumor. To the bestThe Relationship Between the MTDH (2470G.A) Polymorphism and MTDH Protein LevelsWe further TA02 studied the possible relationship between the MTDH (2470G.A) polymorphism and the MTDH protein expressionFigure 1. Sequencing purchase TA-01 chromatograms of MTDH (2470G.A). A , the sequencing chromatogram results of the genotype GG, GA and AA respectively. Samples were chosen randomly. doi:10.1371/journal.pone.0051561.gMTDH and Ovarian Cancer SusceptibilityTable 2. Results of association analysis between rs16896059 and clinicopathological characteristics.Clinical data informationAll( )Genotype GG( ) GA+AA( )P-valueORAge #50 .50 Degree of Differentiation Low Middle High Clinical stage I II III IV Positive lymph node Negative Positive CA125 #65(U/ml) .65(U/ml) Size of tumor ,10 cm 10 cm Tumor histology Serous Other doi:10.1371/journal.pone.0051561.t002 89(65.4) 47(34.6) 58(42.6) 30(22.1) 31(22.8) 17(12.5) 0.877 1.00(reference) 0.943 80(59.3) 55(40.7) 54(40.0) 34(25.2) 26(19.3) 21(15.6) 0.496 1.00(reference) 0.780 23(17.6) 108(82.4) 15(11.5) 71(54.2) 8(6.11) 37(28.2) 0.962 1.00(reference) 1.023 37(66.1) 19(33.9) 20(35.7) 12(21.4) 17(30.4) 7(12.5) 0.515 1.00(reference) 1.457 36(28.8) 89(71.2) 18(14.4) 62(49.6) 18(14.4) 27(21.6) 0.038 1.00(reference) 2.296 89(84.0) 17(16.0) 58(54.7) 10(9.43) 31(29.2) 7(6.60) 0.617 1.00(reference) 0.764 43(31.9) 92(68.1) 31(23.0) 61(45.2) 12(8.89) 31(23.0) 0.608 1.00(reference) 1.of our knowledge, this is the first variant association study of MTDH SNPs and ovarian cancer risk. We expect that 1379592 MTDH will be a useful molecular marker for assessing ovarian cancer risk and for predicting ovarian cancer patient prognosis. However, this finding should be verified in a larger sample. The SNP rs16896059 is located in the promoter of MTDH and thus polymorphisms do not alter the sequence or structure of the protein. We investigated the protein expression level of MTDH by western blotting. As previously reported, the expression levels of MTDH in ovarian cancer tissues were significantly.Node metastasis, CA125 expression, tumor size and tumor histology. A statistically significant association with clinical stage was found (P = 0.038). No relationships between the polymorphism and age at diagnosis, degree of tumor differentiation, lymph node metastasis, CA125 expression, tumor size or tumor histology were found. Thus, the MTDH (2470G.A) polymorphism may be an indicator of clinical stage in ovarian cancer.level in vivo. As shown in Fig. 2, the levels of MTDH protein in 15 ovarian cancer tissues were significantly higher than those in 17 normal tissues (P,0.01). As shown in Fig. 2B and 2C, the MTDH protein expression was higher in patients with the GG or GA genotypes than in those with the AA genotype, but these differences were not significant (P.0.05). These findings suggest that the SNP 2470G.A may not significantly impact the expression of the MTDH gene.DiscussionMTDH plays a critical role in tumor biology, and it is involved in a variety of tumor biological behaviors. Our group was the first to discover a significant association between MTDH and tumor susceptibility: that is, that 2 MTDH variants are associated with breast cancer [34]. In this study, we further analyzed various SNPs in MTDH and found another SNP (rs16896059, 2470G.A) with statistically significant differences between ovarian cancer case and control groups. Furthermore, rs16896059 was statistically significantly associated with the clinical stage of the tumor. To the bestThe Relationship Between the MTDH (2470G.A) Polymorphism and MTDH Protein LevelsWe further studied the possible relationship between the MTDH (2470G.A) polymorphism and the MTDH protein expressionFigure 1. Sequencing chromatograms of MTDH (2470G.A). A , the sequencing chromatogram results of the genotype GG, GA and AA respectively. Samples were chosen randomly. doi:10.1371/journal.pone.0051561.gMTDH and Ovarian Cancer SusceptibilityTable 2. Results of association analysis between rs16896059 and clinicopathological characteristics.Clinical data informationAll( )Genotype GG( ) GA+AA( )P-valueORAge #50 .50 Degree of Differentiation Low Middle High Clinical stage I II III IV Positive lymph node Negative Positive CA125 #65(U/ml) .65(U/ml) Size of tumor ,10 cm 10 cm Tumor histology Serous Other doi:10.1371/journal.pone.0051561.t002 89(65.4) 47(34.6) 58(42.6) 30(22.1) 31(22.8) 17(12.5) 0.877 1.00(reference) 0.943 80(59.3) 55(40.7) 54(40.0) 34(25.2) 26(19.3) 21(15.6) 0.496 1.00(reference) 0.780 23(17.6) 108(82.4) 15(11.5) 71(54.2) 8(6.11) 37(28.2) 0.962 1.00(reference) 1.023 37(66.1) 19(33.9) 20(35.7) 12(21.4) 17(30.4) 7(12.5) 0.515 1.00(reference) 1.457 36(28.8) 89(71.2) 18(14.4) 62(49.6) 18(14.4) 27(21.6) 0.038 1.00(reference) 2.296 89(84.0) 17(16.0) 58(54.7) 10(9.43) 31(29.2) 7(6.60) 0.617 1.00(reference) 0.764 43(31.9) 92(68.1) 31(23.0) 61(45.2) 12(8.89) 31(23.0) 0.608 1.00(reference) 1.of our knowledge, this is the first variant association study of MTDH SNPs and ovarian cancer risk. We expect that 1379592 MTDH will be a useful molecular marker for assessing ovarian cancer risk and for predicting ovarian cancer patient prognosis. However, this finding should be verified in a larger sample. The SNP rs16896059 is located in the promoter of MTDH and thus polymorphisms do not alter the sequence or structure of the protein. We investigated the protein expression level of MTDH by western blotting. As previously reported, the expression levels of MTDH in ovarian cancer tissues were significantly.
