Mage genes independent biomarker for prognosis 14-02-2012

Correlation between methylation and gene expression

(For organizing data)

Search/collect data• 1, correlation of methylation and

gene expression.

• 2, correlation of MAGE genes

expression and HLA alelles

expression (which indicate HLA may present the MAGE CTA).

• 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

y = 0.011x - 0.353R² = 0.050

-2

0

2

4

6

0 50 100MA

GEA

1

HLA-DMB

MAGEA1

y = -0.008x

+ 0.201R² =

0.130

-1.5

-1

-0.5

0

0.5

1

1.5

0 100Axi

s Ti

tle

HLA-DOB

MAGEB10

y = -1.704x + 1.308R² = 0.039

-1

-0.5

0

0.5

1

1.5

2

2.5

3

3.5

4

0 0.2 0.4 0.6 0.8 1

Ge

ne

exp

ress

ion

Methylation

MAGEB2

y = -0.335x + 0.272R² = 0.070

-0.3

-0.2

-0.1

0

0.1

0.2

0.3

0.4

0.5

0 0.2 0.4 0.6 0.8 1Ge

ne

exp

ress

ion

Methylation

MAGEA2B

y = -0.121x + 0.083R² = 0.021

-0.3

-0.2

-0.1

0

0.1

0.2

0.3

0.4

0.5

0 0.2 0.4 0.6 0.8 1

Ge

ne

exp

ress

ion

(2

nd

)

Methylation

MAGEA2B

y = 0.882x - 0.136R² = 0.039

-1.5

-1

-0.5

0

0.5

1

1.5

0 0.1 0.2 0.3 0.4

Ge

ne

exp

ress

ion

Methylation

MAGED2

Methylation inhibited the MAGEB2 expression, increase life span

y = -1.096x + 0.786R² = 0.055

-1

-0.5

0

0.5

1

1.5

2

2.5

3

3.5

4

0 0.2 0.4 0.6 0.8 1

Axi

s Ti

tle

Axis Title

MAGEB2

y = 0.135x - 0.031R² = 0.001

-1

-0.5

0

0.5

1

1.5

2

0 0.2 0.4 0.6 0.8 1

Ge

ne

Exp

ress

ion

Methylation

MAGEA11

y = 0.628x - 0.167R² = 0.021

-1

-0.5

0

0.5

1

1.5

2

0 0.1 0.2 0.3 0.4 0.5 0.6Ge

ne

exp

ress

ion

(2

nd

)

Methylation

MAGEA11

y = 0.736x - 0.102R² = 0.049

-0.8

-0.6

-0.4

-0.2

0

0.2

0.4

0.6

0.8

1

1.2

0 0.05 0.1 0.15 0.2 0.25 0.3 0.35Ge

ne

exp

ress

ion

Methylation

MAGEH1

y = 0.331x - 0.086R² = 0.022

-0.8

-0.6

-0.4

-0.2

0

0.2

0.4

0.6

0.8

1

1.2

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7

Ge

ne

exp

ress

ion

(2

nd

)

Methylation

MAGEH1

y = -0.276x + 0.239R² = 0.001

-1

-0.5

0

0.5

1

1.5

2

2.5

3

0 0.2 0.4 0.6 0.8 1

Ge

ne

exp

ress

ion

Methylation

MAGEA12

y = -0.435x + 0.320R² = 0.002

-1

-0.5

0

0.5

1

1.5

2

2.5

3

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8

Ge

ne

exp

ress

ion

Methylation

MAGEA12

y = -0.309x + 0.2R² = 0.000

-2

-1.5

-1

-0.5

0

0.5

1

1.5

2

2.5

0 0.05 0.1 0.15 0.2 0.25

Ge

ne

exp

ress

ion

Methylation

MAGED1

y = -0.567x + 0.235R² = 0.005

-2

-1.5

-1

-0.5

0

0.5

1

1.5

2

2.5

0 0.1 0.2 0.3 0.4

Ge

ne

exp

ress

ion

Methylation

MAGED1

y = -3,7562x + 3,1755R² = 0,4691

-1

-0.5

0

0.5

1

1.5

2

2.5

3

3.5

0 0.2 0.4 0.6 0.8 1

Ge

ne

exp

ress

ion

Methylation

MAGEC1

y = -2.115x + 1.684R² = 0.193

-1

-0.5

0

0.5

1

1.5

2

2.5

3

3.5

0 0.2 0.4 0.6 0.8 1 1.2

Ge

ne

exp

ress

ion

Methylation

MAGEC1

P=0,1274

Methylation inhibits the MAGEC1 expression, increased survivals

y = -3.594x + 3.176R² = 0.143

-2

-1

0

1

2

3

4

5

0 0.2 0.4 0.6 0.8 1 1.2

Ge

ne

exp

ress

ion

Methylation

MAGEA10

y = -1.697x + 1.276R² = 0.110

-1

-0.5

0

0.5

1

1.5

2

2.5

3

3.5

4

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

Ge

ne

exp

ress

ion

Methylation

MAGEA8

y = -4.002x + 3.595R² = 0.138

-2

-1

0

1

2

3

4

5

0 0.2 0.4 0.6 0.8 1 1.2

Ge

ne

exp

ress

ion

Methylation

MAGEA10

y = 0.184x - 0.044R² = 0.023

-0.4

-0.3

-0.2

-0.1

0

0.1

0.2

0.3

0.4

0 0.1 0.2 0.3 0.4 0.5Axi

s Ti

tle

Axis Title

MAGEE1

y = 0.115x - 0.020R² = 0.022

-0.4

-0.3

-0.2

-0.1

0

0.1

0.2

0.3

0.4

0 0.1 0.2 0.3 0.4 0.5 0.6Axi

s Ti

tle

Axis Title

MAGEE1

y = -0.038x + 0.022R² = 0.001

-0.4

-0.3

-0.2

-0.1

0

0.1

0.2

0.3

0.4

0 0.2 0.4 0.6 0.8 1Axi

s Ti

tle

Axis Title

MAGEA5

y = -0.028x + 0.023R² = 0.000

-0.4

-0.3

-0.2

-0.1

0

0.1

0.2

0.3

0.4

0 0.2 0.4 0.6 0.8 1Axi

s Ti

tle

Axis Title

MAGEA5

y = 0.140x - 0.075R² = 0.019

-0.4

-0.3

-0.2

-0.1

0

0.1

0.2

0.3

0.4

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8Axi

s Ti

tle

Axis Title

MAGEB3

y = 0.195x - 0.071R² = 0.026

-0.4

-0.3

-0.2

-0.1

0

0.1

0.2

0.3

0.4

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7Axi

s Ti

tle

Axis Title

MAGEB3

y = -0.365x + 0.248R² = 0.130

-0.4

-0.3

-0.2

-0.1

0

0.1

0.2

0.3

0.4

0 0.2 0.4 0.6 0.8 1Axi

s Ti

tle

Axis Title

MAGEA6

y = -0.371x + 0.260R² = 0.144

-0.4

-0.3

-0.2

-0.1

0

0.1

0.2

0.3

0.4

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1Axi

s Ti

tle

Axis Title

MAGEA6

y = 0.223x - 0.114R² = 0.067

-0.4

-0.3

-0.2

-0.1

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8

Axi

s Ti

tle

Axis Title

MAGEB4

y = 0.246x - 0.157R² = 0.104

-0.4

-0.3

-0.2

-0.1

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0 0.2 0.4 0.6 0.8 1

Axi

s Ti

tle

Axis Title

MAGEB4

y = -0.128x + 0.025R² = 0.016

-0.4

-0.3

-0.2

-0.1

0

0.1

0.2

0.3

0.4

0.5

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7

Axi

s Ti

tle

Axis Title

MAGEE2

y = -3.405x + 2.928R² = 0.037

-2

-1

0

1

2

3

4

5

0 0.2 0.4 0.6 0.8 1

Axi

s Ti

tle

Axis Title

MAGEA9B

y = 0.027x - 0.034R² = 0.001

-0.3

-0.25

-0.2

-0.15

-0.1

-0.05

0

0.05

0.1

0.15

0.2

0.25

0 0.2 0.4 0.6 0.8 1

Axi

s Ti

tle

Axis Title

MAGEB18

y = -0.003x + 0.001R² = 2E-05

-0.5

-0.4

-0.3

-0.2

-0.1

0

0.1

0.2

0.3

0.4

0 0.2 0.4 0.6 0.8 1

Axi

s Ti

tle

Axis Title

MAGEC3

y = -0.000x + 0.000R² = 1E-06

-0.5

-0.4

-0.3

-0.2

-0.1

0

0.1

0.2

0.3

0.4

0 0.2 0.4 0.6 0.8 1

Axi

s Ti

tle

Axis Title

MAGEC3

y = -0.309x + 0.2R² = 0.000

-2

-1.5

-1

-0.5

0

0.5

1

1.5

2

2.5

0 0.05 0.1 0.15 0.2 0.25

Axi

s Ti

tle

Axis Title

MAGED1

y = 0.882x - 0.136R² = 0.039

-1.5

-1

-0.5

0

0.5

1

1.5

0 0.05 0.1 0.15 0.2 0.25 0.3 0.35 0.4Axi

s Ti

tle

Axis Title

MAGED2

y = -1.651x + 0.416R² = 0.121

-2

-1.5

-1

-0.5

0

0.5

1

1.5

2

2.5

3

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7

Axi

s Ti

tle

Axis Title

MAGED4 (2)

y = -1.886x + 0.367R² = 0.066

-2

-1.5

-1

-0.5

0

0.5

1

1.5

2

2.5

3

0 0.1 0.2 0.3 0.4 0.5 0.6

Axi

s Ti

tle

Axis Title

MAGED4 (1)

Km5

P=0,0703

Km2

Km7

Km1

Km3

Km4

P=0,0734

Km6

P=0.0026

Correlation of methylation and gene expression

(A) Correlation between ID4 expression and ID4 promoter methylation in human breast cancer

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 ).

Methylation headmap of MAGE genes?

MAGE antigen presented by HLA alelles?

y = 0.011x - 0.353R² = 0.050

-2

-1

0

1

2

3

4

5

0 20 40 60 80 100

MA

GEA

1

HLA-DMB

MAGEA1

y = 0.009x - 0.178R² = 0.034

-2

-1

0

1

2

3

4

0 20 40 60 80 100

Axi

s Ti

tle

Axis Title

MAGEA3

y = 0.000x - 0.015R² = 0.017

-0.4

-0.3

-0.2

-0.1

0

0.1

0.2

0.3

0.4

0 20 40 60 80 100Axi

s Ti

tle

HLA-DMB

MAGEA5

y = 0.004x + 0.103R² = 0.016

-2

-1.5

-1

-0.5

0

0.5

1

1.5

2

2.5

3

0 20 40 60 80 100

Axi

s Ti

tle

HLA-DMB

MAGED4

y = 0.002x - 0.118R² = 0.051

-0.8

-0.6

-0.4

-0.2

0

0.2

0.4

0.6

0.8

1

1.2

0 20 40 60 80 100

Axi

s Ti

tle

HLA-DMB

MAGEH1

y = -0.001x + 0.042R² = 0.055

-0.4

-0.3

-0.2

-0.1

0

0.1

0.2

0.3

0.4

0 20 40 60 80 100Axi

s Ti

tle

HLA-DMB

MAGEE1

HLA-DOB

y = 0.000x - 0.018R² = 0.013

-0.5

0

0.5

0 20 40 60 80 100Axi

s Ti

tle

HLA-DOB

MAGEE2y = -0.000x + 0.029

R² = 0.054

-0.3

-0.25

-0.2

-0.15

-0.1

-0.05

0

0.05

0.1

0.15

0.2

0.25

0 20 40 60 80 100

Axi

s Ti

tle

HLA-DOB

MAGEB18

y = 0.011x - 0.353R² = 0.050

-2

0

2

4

6

0 20 40 60 80 100

Axi

s Ti

tle

HLA-DOB

MAGEA1

y = 0.004x + 0.103R² = 0.016

-2

-1.5

-1

-0.5

0

0.5

1

1.5

2

2.5

3

0 20 40 60 80 100

Axi

s Ti

tle

HLA-DOB

MAGED4

y = -0.008x + 0.201R² = 0.130

-2

0

2

0 20 40 60 80 100Axi

s Ti

tle

Axis Title

MAGEB10

HLA-DRA

y = 0.011x - 0.353R² = 0.050

-2

0

2

4

6

0 20 40 60 80 100

Axi

s Ti

tle

HLA-DRA

MAGEA1

y = 0.009x - 0.178R² = 0.034

-2

-1

0

1

2

3

4

0 20 40 60 80 100

Axi

s Ti

tle

HLA-DRA

MAGEA3

y = 0.013x - 0.344R² = 0.04

-2

-1

0

1

2

3

4

5

0 20 40 60 80 100

Axi

s Ti

tle

HLA-DRA

MAGEA9B

y = -0.000x + 0.037R² = 0.025

-0.4

-0.3

-0.2

-0.1

0

0.1

0.2

0.3

0.4

0 20 40 60 80 100Axi

s Ti

tle

Axis Title

MAGEB3

y = -0.001x + 0.042R² = 0.055

-0.5

0

0.5

0 20 40 60 80 100Axi

s Ti

tle

Axis Title

MAGEE1

HLA-C

y = -0.000x + 0.029R² = 0.054

-0.3

-0.2

-0.1

0

0.1

0.2

0.3

0 20 40 60 80 100Axi

s Ti

tle

HLA-C

MAGEB18

y = 0.011x - 0.353R² = 0.050

-2

-1

0

1

2

3

4

5

0 20 40 60 80 100

Axi

s Ti

tle

HLA-C

MAGEA1

y = 0.011x - 0.353R² = 0.050

-2

0

2

4

6

0 50 100

Axi

s Ti

tle

HLA-C

MAGEA1

y = 0.007x - 0.184R² = 0.037

-1

0

1

2

3

0 20 40 60 80 100

Axi

s Ti

tle

HLA-C

MAGEA12

y = 0.013x - 0.344R² = 0.04

-2

0

2

4

6

0 20 40 60 80 100

Axi

s Ti

tle

Axis Title

MAGEA9B

y = 0.002x - 0.118R² = 0.051

-0.8

-0.6

-0.4

-0.2

0

0.2

0.4

0.6

0.8

1

1.2

0 20 40 60 80 100

Axi

s Ti

tle

HLA-C

MAGEH1

y = -0.001x + 0.042R² = 0.055

-0.5

0

0.5

0 50 100Axi

s Ti

tle

Axis Title

MAGEE1

HLA-By = -0.000x + 0.029R² = 0.054

-0.3

-0.2

-0.1

0

0.1

0.2

0.3

0 50 100Axi

s Ti

tle

HLA-B

MAGEB18

MAGEE1 The 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.

http://www.ncbi.nlm.nih.gov/nuccore/291190813?from=5279&to=8152

MAGEC1Homo sapiens melanoma antigen family C, 1 (MAGEC1), RefSeqGene on chromosome X.

Homo sapiens melanoma antigen family A, 2B (MAGEA2B), mRNA

Homo sapiens melanoma antigen family A, 11 (MAGEA11), RefSeqGene on chromosome X

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

Homo sapiens melanoma antigen family C, 3 (MAGEC3), RefSeqGene on chromosome X


Homo sapiens melanoma antigen family D, 1 (MAGED1), RefSeqGene on chromosome XNCBI Reference Sequence: NG_012559.1

Homo sapiens melanoma antigen family H, 1 (MAGEH1), RefSeqGene

on chromosome XNCBI Reference Sequence:

NG_013248.1

Homo sapiens melanoma antigen family D, 2 (MAGED2), RefSeqGene on chromosome XNCBI Reference Sequence: NG_012844.1

Homo sapiens melanoma antigen family B, 4 (MAGEB4), RefSeqGene on chromosome XNCBI Reference Sequence: NG_015870.1





There are 1 possible CpG island(s) found.

Homo sapiens melanoma antigen family A, 6 (MAGEA6), transcript variant 2, mRNANCBI Reference Sequence: NM_175868.1



Homo sapiens MAGED4 protein (MAGED4) mRNA, complete cdsGenBank: AF329733.1


http://www.urogene.org/methprimer

http://www.urogene.org/methprimer




Homo sapiens melanoma antigen family C, 2 (MAGEC2), RefSeqGene on chromosome X




PREDICTED: Homo sapiens melanoma antigen family B, 5 (MAGEB5), mRNANCBI Reference Sequence: XM_293407.7



Homo sapiens melanoma antigen family A, 9 (MAGEA9), mRNANCBI Reference Sequence: NM_005365.4

Technology

Mage genes independent biomarker for prognosis 14-02-2012