Mage genes independent biomarker for prognosis 14-02-2012

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Mage genes independent biomarker for prognosis 14-02-2012

  1. 1. Correlation between methylation and gene expression (For organizing data)
  2. 2. Search/collect data• 1, correlation of methylation and gene expression. MAGEA1 y = 0.011x - 0.353 6 MAGEB10• 2, correlation of MAGE genes R² = 0.050 y=- 4 1.5 0.008x 2 MAGEA1 + 0 1 0.201 expression and HLA alelles -2 0 50 100 0.5 R² = Axis Title 0.130 HLA-DMB 0 -0.5 0 100 expression ( ). which indicate HLA may present the MAGE CTA -1 -1.5 HLA-DOB• 3, K-M analysis (survival curve)• 4, Prediction and stringency of antigenic epitopes of MAGE genes after targeted MAGE gene determined.• 5, Palindrome 2-D structure of targeted MAGE genes• 6, MAGE gene expression distribution in Estonia cohort
  3. 3. MAGEA2B MAGEA2B 0.5 0.5 0.4 Gene expression (2nd ) 0.4 0.3 y = -0.121x + 0.083 y = -0.335x + 0.272 R² = 0.021 0.3 0.2 Gene expression R² = 0.070 0.2 0.1 0.1 0 0 -0.1 0 0.2 0.4 0.6 0.8 -0.1 0 0.2 0.4 0.6 0.8 1 -0.2 -0.2 -0.3 -0.3 Methylation Methylation 4 3.5 MAGEB2 3 MAGED2 2.5 1.5 2Gene expression y = 0.882x - 0.136 y = -1.704x + 1.308 1 R² = 0.039 1.5 R² = 0.039 Gene expression 0.5 1 0.5 0 0 0 0.1 0.2 0.3 0.4 -0.5 -0.5 0 0.2 0.4 0.6 0.8 1 -1 -1 Methylation -1.5 Methylation Methylation inhibited the MAGEB2 expression, increase life span
  4. 4. MAGEB2 4 3.5 3 2.5 y = -1.096x + 0.786 2 R² = 0.055Axis Title 1.5 1 0.5 0 -0.5 0 0.2 0.4 0.6 0.8 1 -1 Axis Title
  5. 5. MAGEA11 MAGEA11 2 2 1.5 1.5 Gene expression (2nd)Gene Expression 1 y = 0.135x - 0.031 1 y = 0.628x - 0.167 0.5 R² = 0.001 0.5 R² = 0.021 0 0 0 0.2 0.4 0.6 0.8 1 -0.5 0 0.1 0.2 0.3 0.4 0.5 0.6 -0.5 -1 Methylation -1 Methylation MAGEH1 1.2 MAGEH1 1 1.2 0.8 1 y = 0.736x - 0.102 0.8 Gene expression (2nd) Gene expression 0.6 R² = 0.049 0.4 0.6 y = 0.331x - 0.086 0.2 0.4 R² = 0.022 0 0.2 -0.2 0 0.05 0.1 0.15 0.2 0.25 0.3 0.35 0 -0.4 -0.2 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 -0.6 -0.4 -0.8 -0.6 Methylation -0.8 Methylation
  6. 6. MAGED1 MAGED1 2.5 2.5 2 2 y = -0.309x + 0.2 1.5 1.5 R² = 0.000 1 Gene expression Gene expression 1 0.5 0.5 y = -0.567x + 0.235 0 0 R² = 0.005 -0.5 0 0.1 0.2 0.3 0.4 -0.5 0 0.05 0.1 0.15 0.2 0.25 -1 -1 -1.5 -1.5 -2 -2 Methylation Methylation MAGEA12 MAGEA12 3 3 2.5 2.5 y = -0.276x + 0.239 2 R² = 0.001 2 y = -0.435x + 0.320 Gene expression R² = 0.002Gene expression 1.5 1.5 1 1 0.5 0.5 0 0 -0.5 0 0.2 0.4 0.6 0.8 1 -0.5 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 -1 Methylation -1 Methylation
  7. 7. MAGEC1 3.5 3 2.5 P=0,1274 Gene expression 2 y = -3,7562x + 3,1755 1.5 R² = 0,4691 1 0.5 0 -0.5 0 0.2 0.4 0.6 0.8 1 -1 Methylation Methylation inhibits the MAGEC1 expression, increased survivals MAGEC1 3.5 3 2.5Gene expression 2 1.5 y = -2.115x + 1.684 1 R² = 0.193 0.5 0 -0.5 0 0.2 0.4 0.6 0.8 1 1.2 -1 Methylation
  8. 8. MAGEA8 4 3.5 3 2.5 y = -1.697x + 1.276 Gene expression R² = 0.110 2 1.5 1 0.5 0 -0.5 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 -1 Methylation MAGEA10 MAGEA10 5 5 4 4 y = -3.594x + 3.176 R² = 0.143 3 y = -4.002x + 3.595 3Gene expression Gene expression R² = 0.138 2 2 1 1 0 0 0 0.2 0.4 0.6 0.8 1 1.2 0 0.2 0.4 0.6 0.8 1 1.2 -1 -1 -2 -2 Methylation Methylation
  9. 9. MAGEE1 0.4 y = 0.184x - 0.044 0.3 R² = 0.023 0.2 0.1Axis Title 0 -0.1 0 0.1 0.2 0.3 0.4 0.5 -0.2 -0.3 -0.4 Axis Title MAGEE1 0.4 y = 0.115x - 0.020 0.3 R² = 0.022 0.2 0.1 Axis Title 0 -0.1 0 0.1 0.2 0.3 0.4 0.5 0.6 -0.2 -0.3 -0.4 Axis Title
  10. 10. MAGEA5 0.4 0.3 0.2 y = -0.038x + 0.022 R² = 0.001 0.1Axis Title 0 -0.1 0 0.2 0.4 0.6 0.8 1 -0.2 -0.3 -0.4 Axis Title MAGEA5 0.4 y = -0.028x + 0.023 0.3 R² = 0.000 0.2 0.1 Axis Title 0 -0.1 0 0.2 0.4 0.6 0.8 1 -0.2 -0.3 -0.4 Axis Title
  11. 11. MAGEB3 0.4 0.3 y = 0.140x - 0.075 0.2 R² = 0.019 0.1Axis Title 0 -0.1 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 -0.2 -0.3 -0.4 Axis Title MAGEB3 0.4 0.3 y = 0.195x - 0.071 0.2 R² = 0.026 0.1 Axis Title 0 -0.1 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 -0.2 -0.3 -0.4 Axis Title
  12. 12. MAGEA6 y = -0.365x + 0.248 0.4 R² = 0.130 0.3 0.2 0.1Axis Title 0 0 0.2 0.4 0.6 0.8 1 -0.1 -0.2 -0.3 -0.4 Axis Title MAGEA6 0.4 0.3 y = -0.371x + 0.260 R² = 0.144 0.2 0.1 Axis Title 0 -0.1 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 -0.2 -0.3 -0.4 Axis Title
  13. 13. MAGEB4 0.7 0.6 0.5 y = 0.223x - 0.114 0.4 R² = 0.067 0.3Axis Title 0.2 0.1 0 -0.1 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 -0.2 -0.3 -0.4 Axis Title MAGEB4 0.7 0.6 0.5 0.4 y = 0.246x - 0.157 0.3 R² = 0.104 Axis Title 0.2 0.1 0 -0.1 0 0.2 0.4 0.6 0.8 1 -0.2 -0.3 -0.4 Axis Title
  14. 14. Axis Title MAGEE20.50.4 y = -0.128x + 0.025 MAGEA9B0.3 R² = 0.016 50.2 40.1 3 y = -3.405x + 2.928 0 R² = 0.037 Axis Title-0.1 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 2-0.2 1-0.3 0-0.4 0 0.2 0.4 0.6 0.8 1 Axis Title -1 -2 Axis Title MAGEB18 0.25 0.2 y = 0.027x - 0.034 0.15 R² = 0.001 0.1 0.05 Axis Title 0 -0.05 0 0.2 0.4 0.6 0.8 1 -0.1 -0.15 -0.2 -0.25 -0.3 Axis Title
  15. 15. MAGEC3 MAGEC3 0.4 0.4 0.3 0.3 0.2 0.2 0.1 0.1 Axis Title y = -0.003x + 0.001Axis Title y = -0.000x + 0.000 0 0 R² = 2E-05 R² = 1E-06 -0.1 0 0.2 0.4 0.6 0.8 1 -0.1 0 0.2 0.4 0.6 0.8 1 -0.2 -0.2 -0.3 -0.3 -0.4 -0.4 -0.5 -0.5 Axis Title Axis Title
  16. 16. 1.5 MAGED1 1 MAGED2 2.5 2 0.5 y = 0.882x - 0.136 Axis Title 1.5 R² = 0.039 0 1 0 0.05 0.1 0.15 0.2 0.25 0.3 0.35 0.4Axis Title 0.5 -0.5 y = -0.309x + 0.2 0 R² = 0.000 -1 -0.5 0 0.05 0.1 0.15 0.2 0.25 -1 -1.5 Axis Title -1.5 -2 Axis Title
  17. 17. MAGED4 (1) 3 2.5 2 1.5 MAGED4 (2) 1Axis Title 3 0.5 2.5 0 2 -0.5 0 0.1 0.2 0.3 y = -1.886x + 0.367 0.5 0.4 0.6 R² = 0.066 1.5 -1 1 Axis Title -1.5 0.5 -2 Axis Title 0 -0.5 0 0.1 0.2 0.3 0.4 y = -1.651x + 0.416 0.5 0.6 0.7 -1 R² = 0.121 -1.5 -2 Axis Title
  18. 18. P=0,0703Km5
  19. 19. Km2
  20. 20. Km7
  21. 21. Km1
  22. 22. Km3
  23. 23. Km4 P=0,0734
  24. 24. Km6 P=0.0026
  25. 25. Correlation of methylation and gene expression
  26. 26. (A) Correlation between ID4expression and ID4 promotermethylation in human breastcancer For this purpose, a part of the same breast cancer cohort (n = 46) used previously for methylation analysis was re-assessed (Figure 2A ). We found an increased risk for tumour recurrence in breast cancer patients with ID4 promoter methylation (P = 0.036) compared to patients with lack of ID4 methylation (Figure 2B ).
  27. 27. Methylation headmap of MAGE genes?
  28. 28. MAGE antigen presented by HLA alelles? MAGEA1 5 MAGEA3 y = 0.011x - 0.353 4 R² = 0.050 4 3 3 2 Axis Title 2MAGEA1 1 y = 0.009x - 0.178 R² = 0.034 1 0 0 20 40 60 80 100 0 -1 0 20 40 60 80 100 -1 -2 Axis Title -2 HLA-DMB
  29. 29. MAGEA5 MAGED4 0.4 3 0.3 2.5 0.2 2 0.1 1.5 Axis Title y = 0.000x - 0.015 1 Axis Title 0 R² = 0.017 y = 0.004x + 0.103 0.5 R² = 0.016 -0.1 0 20 40 60 80 100 0 -0.2 -0.5 0 20 40 60 80 100 -0.3 -1 -1.5 -0.4 HLA-DMB -2 HLA-DMB MAGEH1 1.2 MAGEE1 1 0.4 0.8 0.3 y = -0.001x + 0.042 0.6 R² = 0.055 0.2 0.4Axis Title Axis Title 0.1 0.2 y = 0.002x - 0.118 0 R² = 0.051 0 -0.2 0 20 40 60 80 100 -0.1 0 20 40 60 80 100 -0.4 -0.2 -0.6 -0.3 -0.8 HLA-DMB -0.4 HLA-DMB
  30. 30. HLA-DOB MAGEE2 MAGEB18 0.25 y = -0.000x + 0.029 0.5 0.2 R² = 0.054 0.15Axis Title y = 0.000x - 0.018 0.1 0 R² = 0.013 0.05 Axis Title 0 20 40 60 80 100 0 -0.5 -0.05 0 20 40 60 80 100 HLA-DOB -0.1 -0.15 -0.2 MAGEA1 -0.25 -0.3 6 HLA-DOB 4 Axis Title 2 y = 0.011x - 0.353 0 R² = 0.050 -2 0 20 40 60 80 100 MAGED4 HLA-DOB 3 2.5 2 1.5 MAGEB10 + 0.201 1 Axis Title y = -0.008x y = 0.004x + 0.103 2 R² = 0.130 0.5 R² = 0.016 Axis Title 0 0 -0.5 0 20 40 60 80 10 0 20 40 60 80 100 -1 -2 -1.5 Axis Title -2 HLA-DOB
  31. 31. HLA-DRA MAGEA1 MAGEA3 4 6 3 4 2 Axis TitleAxis Title 2 1 y = 0.009x - 0.178 y = 0.011x - 0.353 0 R² = 0.034 0 R² = 0.050 -1 0 20 40 60 80 100 0 20 40 60 80 100 -2 -2 HLA-DRA HLA-DRA MAGEE1 0.5 y = -0.001x + 0.042 R² = 0.055 Axis Title 0 0 20 40 60 80 100 MAGEA9B MAGEB3 -0.5 Axis Title 5 0.4 4 0.3 y = -0.000x + 0.037 R² = 0.025 0.2 3 0.1 Axis Title Axis Title 2 0 1 y = 0.013x - 0.344 R² = 0.04 -0.1 0 20 40 60 80 100 0 -0.2 0 20 40 60 80 100 -1 -0.3 -2 -0.4 HLA-DRA Axis Title
  32. 32. y = -0.001x + 0.042 y = 0.013x - 0.344 R² = 0.055 MAGEE1 R² = 0.04 MAGEA9B 0.5 HLA-C 6 Axis Title 4 Axis Title 0 2 0 50 100 0 -0.5 Axis Title -2 0 20 40 60 80 100 MAGEA1 Axis Title 5 MAGEB18 + 0.029 y = -0.000x R² = 0.054 4 0.3 0.2 3 0.1 Axis Title Axis Title 2 0 -0.1 0 20 40 60 80 100 1 y = 0.011x - 0.353 -0.2 R² = 0.050 0 -0.3 HLA-C 0 20 40 60 80 100 -1 MAGEA1= 0.011x - 0.353 y R² = 0.050 -2 6 HLA-C 4 MAGEA12 MAGEH1 Axis Title y = 0.002x - 0.118 2 R² = 0.051 3 1.2 0 1 2 -2 0 50 100 Axis Title 0.8 HLA-C 1 0.6 y = 0.007x - 0.184 0.4 Axis Title 0 R² = 0.037 0.2 0 20 40 60 80 100 0 -1 -0.2 0 HLA-C 20 40 60 80 100 -0.4 -0.6 -0.8 HLA-C
  33. 33. y = -0.000x + 0.029 R² = 0.054 0.3 MAGEB18 HLA-B 0.2 0.1 Axis Title 0 -0.1 0 50 100 -0.2 -0.3 HLA-B
  34. 34. MAGEE1The sequence you input has 13375 nucleotides in length. There are 2 possible CpG island(s) found. Homo sapiens melanoma antigen family E, 1 (MAGEE1), RefSeqGene on chromosome X. CDS 5279..8152 MAGEE2 There are NO possible CpG islands found. Homo sapiens melanoma antigen family E, 2 (MAGEE2), RefSeqGene on chromosome X.
  35. 35. MAGEC1 Homo sapiens melanoma antigen family C, 1 (MAGEC1), RefSeqGene on chromosome X.Homo sapiens melanoma antigen family A, 2B (MAGEA2B), mRNA
  36. 36. Homo sapiens melanoma antigen family A, 11 (MAGEA11), RefSeqGene on chromosome X
  37. 37. Homo sapiens melanoma antigen family A, 10 (MAGEA10), transcript variant 1, mRNA NCBI Reference Sequence: NM_001011543.2 Homo sapiens melanoma antigen family B, 18 (MAGEB18), RefSeqGene on chromosome X NCBI Reference Sequence: NG_016370.1
  38. 38. Homo sapiens melanoma antigen family C, 3 Homo sapiens melanoma antigen family D, 1 (MAGEC3), RefSeqGene on chromosome X (MAGED1), RefSeqGene on chromosome X NCBI Reference Sequence: NG_012559.1NCBI Reference Sequence: NG_013272.1
  39. 39. Homo sapiens melanoma antigen Homo sapiens melanoma antigen familyfamily H, 1 (MAGEH1), RefSeqGene D, 2 (MAGED2), RefSeqGene on on chromosome X chromosome X NCBI Reference Sequence: NCBI Reference Sequence: NG_012844.1 NG_013248.1
  40. 40. Homo sapiens melanoma antigen family B, 4(MAGEB4), RefSeqGene on chromosome XNCBI Reference Sequence: NG_015870.1
  41. 41. Homo sapiens melanoma antigen family B, 1 (MAGEB1), RefSeqGene on chromosome X NCBI Reference Sequence: NG_016336.1
  42. 42. Homo sapiens melanoma antigen family A, 3 (MAGEA3), RefSeqGene on chromosome X NCBI Reference Sequence: NG_013244.1 There are 1 possible CpG island(s) found.Homo sapiens melanoma antigen family A, 6 (MAGEA6), transcript variant 2, mRNA NCBI Reference Sequence: NM_175868.1
  43. 43. Homo sapiens melanoma antigen family A, 5 (MAGEA5), RefSeqGene on chromosome X NCBI Reference Sequence: NG_016417.1
  44. 44. Homo sapiens MAGED4 protein (MAGED4) mRNA, complete cds GenBank: AF329733.1 There are 2 possible CpG island(s) found. http://www.urogene.org/methprimer
  45. 45. Homo sapiens melanoma antigen family B, 10 (MAGEB10), RefSeqGene on chromosome X NCBI Reference Sequence: NG_017094.1 There are 1 possible CpG island(s) found.
  46. 46. Homo sapiens melanoma antigen family C, 2 (MAGEC2), RefSeqGene on chromosome X NCBI Reference Sequence: NG_015872.1
  47. 47. Homo sapiens melanoma antigen family B, 2 (MAGEB2), RefSeqGene on chromosome X NCBI Reference Sequence: NG_013246.1 PREDICTED: Homo sapiens melanoma antigen family B, 5 (MAGEB5), mRNA NCBI Reference Sequence: XM_293407.7
  48. 48. Homo sapiens melanoma antigen family A, 12 (MAGEA12), RefSeqGene on chromosome X NCBI Reference Sequence: NG_015852.1Homo sapiens melanoma antigen family A, 9 (MAGEA9), mRNANCBI Reference Sequence: NM_005365.4

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