Background
Methods
Raw data
Identification of DEMis, DELs and DEMs
Prediction of target lncRNAs and mRNAs
Reconstruction of the ceRNA network
Functional enrichment analysis
Hub gene selection and reconstruction of key ceRNA subnetworks
Sample selection for qRT-PCR validation
Patients ID | Pathological diagnosis | TNM | Stagea |
---|---|---|---|
001 | SKCM | T3AN1AM0 | IIIB |
002 | SKCM | T3AN0M0 | IIA |
003 | SKCM | T3BN0M0 | IIB |
004 | SKCM | T2AN0M0 | IA |
005 | SKCM | T1AN0M0 | IA |
006 | SKCM | T1AN0M0 | IA |
007 | SKCM | T2BN0M0 | IIA |
008 | SKCM | T1AN0M0 | IA |
009 | SKCM | T4BN2AM0 | IIIC |
010 | SKCM | T2BN0M0 | IIA |
011 | SKCM | T3AN0M0 | IIA |
012 | SKCM | T3BN0M0 | IIB |
RNA isolation and qRT-PCR
Multivariate cox regression model for survival analysis
Gene | Exon number | Locusa |
---|---|---|
MALAT1 | Exon 1 | Chr 11:65265481–65,265,876 |
Exon 2 | Chr 11:65265159–65,265,336 | |
Exon 3 | Chr 11:65266440–65,271,376 | |
Exon 4 | Chr 11:65273731–65,273,902 | |
LINC00943 | Exon 1 | Chr 12:127221553–127,221,702 |
Exon 2 | Chr 12:127227286–127,228,026 | |
Exon 3 | Chr 12:127229316–127,229,434 | |
Exon 4 | Chr 12:127229552–127,230,800 | |
LINC00261 | Exon 1 | Chr 20:22559148–22,559,280 |
Exon 2 | Chr 20:22548432–22,548,523 | |
Exon 3 | Chr 20:22547321–22,547,443 | |
Exon 4 | Chr 20:22541192–22,545,754 |
Results
Identification of DEMs, DELs and DEMis and reconstruction of the lncRNA-miRNA-mRNA (ceRNA) network
KEGG pathway and GO enrichment analysis of lncRNAs based on the ceRNA network
A | ||||
GO-BP Term | Enrichment Score | Count | % | P-Value |
positive regulation of transcription from RNA polymerase II promoter | 9.446887 | 56 | 13.18 | < 0.001 |
positive regulation of transcription, DNA-templated | 4.759462 | 29 | 6.824 | < 0.001 |
transcription from RNA polymerase II promoter | 3.957811 | 27 | 6.353 | < 0.001 |
negative regulation of transcription from RNA polymerase II promoter | 3.674737 | 33 | 7.765 | < 0.001 |
protein stabilization | 3.580807 | 12 | 2.824 | < 0.001 |
spinal cord development | 3.291952 | 6 | 1.412 | < 0.001 |
heart morphogenesis | 3.157839 | 6 | 1.412 | < 0.001 |
kidney development | 3.144958 | 9 | 2.118 | < 0.001 |
positive regulation of peptidyl-serine phosphorylation | 3.001168 | 8 | 1.882 | < 0.001 |
response to cytokine | 2.967806 | 7 | 1.647 | 0.001 |
regulation of protein localization | 2.967806 | 7 | 1.647 | 0.001 |
regulation of cell-matrix adhesion | 2.914902 | 4 | 0.941 | 0.001 |
negative regulation of cell proliferation | 2.759652 | 20 | 4.706 | 0.002 |
cell migration | 2.732195 | 12 | 2.824 | 0.002 |
insulin receptor signaling pathway | 2.724648 | 8 | 1.882 | 0.002 |
B | ||||
GO-CC Term | Enrichment Score | Count | % | P-Value |
cytosol | 5.793638 | 111 | 26.12 | < 0.001 |
cytoplasm | 4.942099 | 154 | 36.24 | < 0.001 |
nucleoplasm | 4.725908 | 93 | 21.88 | < 0.001 |
nucleus | 4.05725 | 154 | 36.24 | < 0.001 |
membrane | 3.599508 | 73 | 17.18 | < 0.001 |
cytoskeleton | 2.478053 | 18 | 4.235 | 0.003 |
cell-cell adherens junction | 2.302618 | 16 | 3.765 | 0.005 |
cis-Golgi network | 1.888299 | 5 | 1.176 | 0.013 |
cell-cell junction | 1.877361 | 10 | 2.353 | 0.013 |
Golgi apparatus | 1.852153 | 30 | 7.059 | 0.014 |
PcG protein complex | 1.690927 | 4 | 0.941 | 0.02 |
receptor complex | 1.672147 | 8 | 1.882 | 0.021 |
lamellipodium | 1.616858 | 9 | 2.118 | 0.024 |
focal adhesion | 1.603246 | 16 | 3.765 | 0.025 |
perinuclear region of cytoplasm | 1.496331 | 22 | 5.176 | 0.032 |
C | ||||
GO-MF Term | Enrichment Score | Count | % | P-Value |
protein binding | 8.364509 | 260 | 61.18 | < 0.001 |
sequence-specific DNA binding | 4.118515 | 28 | 6.588 | < 0.001 |
beta-catenin binding | 3.946374 | 10 | 2.353 | < 0.001 |
transcription factor activity, sequence-specific DNA binding | 3.635935 | 41 | 9.647 | < 0.001 |
platelet-derived growth factor receptor binding | 3.50464 | 5 | 1.176 | < 0.001 |
transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding | 2.912949 | 15 | 3.529 | 0.001 |
transcription regulatory region sequence-specific DNA binding | 2.667561 | 7 | 1.647 | 0.002 |
protein channel activity | 2.637341 | 4 | 0.941 | 0.002 |
insulin-like growth factor receptor binding | 2.344093 | 4 | 0.941 | 0.005 |
insulin binding | 2.293839 | 3 | 0.706 | 0.005 |
neurotrophin TRKA receptor binding | 2.124416 | 3 | 0.706 | 0.008 |
microtubule binding | 2.037592 | 12 | 2.824 | 0.009 |
N6-methyladenosine-containing RNA binding | 1.984943 | 3 | 0.706 | 0.01 |
small GTPase binding | 1.982255 | 4 | 0.941 | 0.01 |
RNA polymerase II core promoter proximal region sequence-specific DNA binding | 1.726919 | 16 | 3.765 | 0.019 |
D | ||||
KEGG pathway | Enrichment Score | Count | % | P-Value |
PI3K-Akt signaling pathway | 6.144606 | 25 | 5.882 | < 0.001 |
Prostate cancer | 5.389517 | 12 | 2.824 | < 0.001 |
Focal adhesion | 4.815445 | 17 | 4 | < 0.001 |
Proteoglycans in cancer | 4.365137 | 16 | 3.765 | < 0.001 |
Insulin signaling pathway | 4.202316 | 13 | 3.059 | < 0.001 |
Signaling pathways regulating pluripotency of stem cells | 4.141148 | 13 | 3.059 | < 0.001 |
Adherens junction | 3.732503 | 9 | 2.118 | < 0.001 |
Pathways in cancer | 3.709619 | 22 | 5.176 | < 0.001 |
FoxO signaling pathway | 3.670169 | 12 | 2.824 | < 0.001 |
Acute myeloid leukemia | 3.609095 | 8 | 1.882 | < 0.001 |
Thyroid hormone signaling pathway | 3.584028 | 11 | 2.588 | < 0.001 |
Choline metabolism in cancer | 3.353402 | 10 | 2.353 | < 0.001 |
Glioma | 3.20572 | 8 | 1.882 | < 0.001 |
Melanoma | 2.973883 | 8 | 1.882 | 0.001 |
HIF-1 signaling pathway | 2.844366 | 9 | 2.118 | 0.001 |
Hub gene selection
lncRNA-miRNA pairs | miRNA-mRNA pairs | Total number | |
---|---|---|---|
MALAT1 | 9 | 200 | 209 |
LINC00943 | 7 | 202 | 209 |
LINC00261 | 5 | 158 | 163 |
Reconstruction of the MALAT1/LINC00943/LINC00261-miRNA-mRNA subnetworks
A | ||||
GO-BP Term | Enrichment Score | Count | % | P-Value |
positive regulation of transcription from RNA polymerase II promoter | 3.579259 | 20 | 11.43 | < 0.001 |
transcription from RNA polymerase II promoter | 3.106442 | 13 | 7.429 | < 0.001 |
positive regulation of transcription, DNA-templated | 3.091753 | 13 | 7.429 | < 0.001 |
neuroepithelial cell differentiation | 2.894845 | 3 | 1.714 | 0.001 |
positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway | 2.772993 | 4 | 2.286 | 0.002 |
neural tube formation | 2.772164 | 3 | 1.714 | 0.002 |
in utero embryonic development | 2.425229 | 7 | 4 | 0.004 |
kidney development | 2.315189 | 5 | 2.857 | 0.005 |
camera-type eye morphogenesis | 2.158154 | 3 | 1.714 | 0.007 |
regulation of protein localization | 2.092037 | 4 | 2.286 | 0.008 |
inner ear morphogenesis | 2.092037 | 4 | 2.286 | 0.008 |
positive regulation of branching involved in ureteric bud morphogenesis | 2.011071 | 3 | 1.714 | 0.01 |
positive regulation of neuroblast proliferation | 1.967555 | 3 | 1.714 | 0.011 |
negative regulation of transcription from RNA polymerase II promoter | 1.923719 | 13 | 7.429 | 0.012 |
cell migration | 1.922663 | 6 | 3.429 | 0.012 |
B | ||||
GO-CC Term | Enrichment Score | Count | % | P-Value |
cytosol | 3.530641 | 45 | 25.71 | < 0.001 |
nucleus | 3.429028 | 64 | 36.57 | < 0.001 |
nucleoplasm | 3.288165 | 39 | 22.29 | < 0.001 |
cell-cell adherens junction | 2.341584 | 9 | 5.143 | 0.005 |
melanosome | 2.052614 | 5 | 2.857 | 0.009 |
filopodium | 1.71293 | 4 | 2.286 | 0.019 |
PcG protein complex | 1.707154 | 3 | 1.714 | 0.02 |
nuclear chromatin | 1.705842 | 6 | 3.429 | 0.02 |
extracellular exosome | 1.429256 | 32 | 18.29 | 0.037 |
cis-Golgi network | 1.35117 | 3 | 1.714 | 0.045 |
spindle microtubule | 1.314751 | 3 | 1.714 | 0.048 |
cytoplasm | 1.239444 | 52 | 29.71 | 0.058 |
perinuclear region of cytoplasm | 1.205186 | 10 | 5.714 | 0.062 |
membrane | 1.146558 | 25 | 14.29 | 0.071 |
spindle | 1.134303 | 4 | 2.286 | 0.073 |
C | ||||
GO-MF Term | Enrichment Score | Count | % | P-Value |
protein binding | 3.880727 | 95 | 54.29 | < 0.001 |
sequence-specific DNA binding | 3.451663 | 14 | 8 | < 0.001 |
transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding | 3.120112 | 9 | 5.143 | < 0.001 |
RNA polymerase II core promoter proximal region sequence-specific DNA binding | 2.566023 | 10 | 5.714 | 0.003 |
poly(A) RNA binding | 2.27862 | 19 | 10.86 | 0.005 |
transcription factor activity, sequence-specific DNA binding | 1.893028 | 16 | 9.143 | 0.013 |
zinc ion binding | 1.508313 | 17 | 9.714 | 0.031 |
cadherin binding involved in cell-cell adhesion | 1.481723 | 7 | 4 | 0.033 |
transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding | 1.359345 | 4 | 2.286 | 0.044 |
vascular endothelial growth factor receptor 2 binding | 1.315103 | 2 | 1.143 | 0.048 |
N6-methyladenosine-containing RNA binding | 1.249923 | 2 | 1.143 | 0.056 |
mRNA 5′-UTR binding | 1.144306 | 2 | 1.143 | 0.072 |
protein heterodimerization activity | 1.046398 | 8 | 4.571 | 0.09 |
RNA polymerase II regulatory region sequence-specific DNA binding | 1.031152 | 5 | 2.857 | 0.093 |
DNA binding | 1.029587 | 20 | 11.43 | 0.093 |
D | ||||
GO-MF Term | Enrichment Score | Count | % | P-Value |
protein binding | 3.880727 | 95 | 54.29 | < 0.001 |
sequence-specific DNA binding | 3.451663 | 14 | 8 | < 0.001 |
transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding | 3.120112 | 9 | 5.143 | < 0.001 |
RNA polymerase II core promoter proximal region sequence-specific DNA binding | 2.566023 | 10 | 5.714 | 0.003 |
poly(A) RNA binding | 2.27862 | 19 | 10.86 | 0.005 |
transcription factor activity, sequence-specific DNA binding | 1.893028 | 16 | 9.143 | 0.013 |
zinc ion binding | 1.508313 | 17 | 9.714 | 0.031 |
cadherin binding involved in cell-cell adhesion | 1.481723 | 7 | 4 | 0.033 |
transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding | 1.359345 | 4 | 2.286 | 0.044 |
vascular endothelial growth factor receptor 2 binding | 1.315103 | 2 | 1.143 | 0.048 |
N6-methyladenosine-containing RNA binding | 1.249923 | 2 | 1.143 | 0.056 |
mRNA 5′-UTR binding | 1.144306 | 2 | 1.143 | 0.072 |
protein heterodimerization activity | 1.046398 | 8 | 4.571 | 0.09 |
RNA polymerase II regulatory region sequence-specific DNA binding | 1.031152 | 5 | 2.857 | 0.093 |
DNA binding | 1.029587 | 20 | 11.43 | 0.093 |
A | ||||
GO-BP Term | Enrichment Score | Count | % | P-Value |
positive regulation of transcription from RNA polymerase II promoter | 3.413985 | 22 | 12.22 | < 0.001 |
positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway | 2.5522952 | 4 | 2.222 | 0.003 |
negative regulation of transcription from RNA polymerase II promoter | 2.4555568 | 16 | 8.889 | 0.004 |
transcription from RNA polymerase II promoter | 2.4471842 | 13 | 7.222 | 0.004 |
positive regulation of transcription, DNA-templated | 2.4336944 | 13 | 7.222 | 0.004 |
apoptotic process | 2.1092412 | 13 | 7.222 | 0.008 |
negative regulation of translational initiation | 2.064083 | 3 | 1.667 | 0.009 |
protein import into mitochondrial matrix | 1.95711 | 3 | 1.667 | 0.011 |
regulation of protein localization | 1.8821494 | 4 | 2.222 | 0.013 |
response to cytokine | 1.8821494 | 4 | 2.222 | 0.013 |
cellular response to cytokine stimulus | 1.7404426 | 3 | 1.667 | 0.018 |
cell morphogenesis | 1.6784701 | 4 | 2.222 | 0.021 |
positive regulation of mesenchymal cell proliferation | 1.6028585 | 3 | 1.667 | 0.025 |
intracellular protein transport | 1.6019839 | 7 | 3.889 | 0.025 |
protein sumoylation | 1.5991972 | 5 | 2.778 | 0.025 |
B | ||||
GO-CC Term | Enrichment Score | Count | % | P-Value |
cytosol | 4.721026 | 54 | 30 | < 0.001 |
nucleoplasm | 3.468485 | 44 | 24.44 | < 0.001 |
nucleus | 3.459493 | 72 | 40 | < 0.001 |
cytoplasm | 3.448156 | 70 | 38.89 | < 0.001 |
membrane | 2.786622 | 35 | 19.44 | 0.002 |
microtubule plus-end | 1.979181 | 3 | 1.667 | 0.01 |
PcG protein complex | 1.593489 | 3 | 1.667 | 0.025 |
nuclear chromatin | 1.476598 | 6 | 3.333 | 0.033 |
intracellular ribonucleoprotein complex | 1.428852 | 5 | 2.778 | 0.037 |
mitochondrial outer membrane | 1.3075 | 5 | 2.778 | 0.049 |
endoplasmic reticulum membrane | 1.253057 | 14 | 7.778 | 0.056 |
perinuclear region of cytoplasm | 1.207393 | 11 | 6.111 | 0.062 |
MLL5-L complex | 1.146143 | 2 | 1.111 | 0.071 |
mitochondrial inner membrane presequence translocase complex | 1.096965 | 2 | 1.111 | 0.08 |
C | ||||
GO-MF Term | Enrichment Score | Count | % | P-Value |
protein binding | 3.972219 | 109 | 60.56 | < 0.001 |
protein channel activity | 3.7469 | 4 | 2.222 | < 0.001 |
sequence-specific DNA binding | 3.320627 | 15 | 8.333 | < 0.001 |
RNA polymerase II core promoter proximal region sequence-specific DNA binding | 2.640286 | 11 | 6.111 | 0.002 |
transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding | 2.106865 | 8 | 4.444 | 0.008 |
transcription factor activity, sequence-specific DNA binding | 1.648871 | 17 | 9.444 | 0.022 |
protein kinase activity | 1.643895 | 9 | 5 | 0.023 |
ATP binding | 1.307149 | 22 | 12.22 | 0.049 |
vascular endothelial growth factor receptor 2 binding | 1.25008 | 2 | 1.111 | 0.056 |
transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding | 1.197916 | 4 | 2.222 | 0.063 |
N6-methyladenosine-containing RNA binding | 1.185193 | 2 | 1.111 | 0.065 |
P-P-bond-hydrolysis-driven protein transmembrane transporter activity | 1.129258 | 2 | 1.111 | 0.074 |
poly(A) RNA binding | 1.119963 | 17 | 9.444 | 0.076 |
chromatin binding | 1.08038 | 8 | 4.444 | 0.083 |
mRNA 5′-UTR binding | 1.080159 | 2 | 1.111 | 0.083 |
D | ||||
KEGG pathway | Enrichment Score | Count | % | P-Value |
Pathways in cancer | 2.26453 | 11 | 6.111 | 0.005 |
PI3K-Akt signaling pathway | 2.145933 | 10 | 5.556 | 0.007 |
Oocyte meiosis | 1.604046 | 5 | 2.778 | 0.025 |
Pancreatic cancer | 1.566902 | 4 | 2.222 | 0.027 |
Platelet activation | 1.386975 | 5 | 2.778 | 0.041 |
Insulin signaling pathway | 1.307592 | 5 | 2.778 | 0.049 |
Proteoglycans in cancer | 1.304184 | 6 | 3.333 | 0.05 |
Focal adhesion | 1.259046 | 6 | 3.333 | 0.055 |
Rap1 signaling pathway | 1.229991 | 6 | 3.333 | 0.059 |
Hippo signaling pathway | 1.190921 | 5 | 2.778 | 0.064 |
MicroRNAs in cancer | 1.179653 | 7 | 3.889 | 0.066 |
HIF-1 signaling pathway | 1.146419 | 4 | 2.222 | 0.071 |
Vibrio cholerae infection | 1.020041 | 3 | 1.667 | 0.095 |
A | ||||
GO-BP Term | Enrichment Score | Count | % | P-Value |
positive regulation of transcription from RNA polymerase II promoter | 4.294676 | 19 | 14.29 | < 0.001 |
transcription from RNA polymerase II promoter | 3.946596 | 13 | 9.774 | < 0.001 |
neuroepithelial cell differentiation | 3.074302 | 3 | 2.256 | < 0.001 |
spinal cord development | 3.033527 | 4 | 3.008 | 0.001 |
neural tube formation | 2.951191 | 3 | 2.256 | 0.001 |
inner ear morphogenesis | 2.342119 | 4 | 3.008 | 0.005 |
regulation of protein localization | 2.342119 | 4 | 3.008 | 0.005 |
regulation of neuron differentiation | 2.141452 | 3 | 2.256 | 0.007 |
regulation of transforming growth factor beta receptor signaling pathway | 2.141452 | 3 | 2.256 | 0.007 |
protein stabilization | 1.937969 | 5 | 3.759 | 0.012 |
fungiform papilla morphogenesis | 1.892035 | 2 | 1.504 | 0.013 |
stem cell differentiation | 1.887589 | 3 | 2.256 | 0.013 |
regulation of signal transduction | 1.799832 | 3 | 2.256 | 0.016 |
negative regulation of transcription from RNA polymerase II promoter | 1.756023 | 11 | 8.271 | 0.018 |
myotome development | 1.717328 | 2 | 1.504 | 0.019 |
B | ||||
GO-CC Term | Enrichment Score | Count | % | P-Value |
nucleus | 4.161906 | 55 | 41.35 | < 0.001 |
nucleoplasm | 3.062718 | 32 | 24.06 | < 0.001 |
cytoplasm | 3.032352 | 50 | 37.59 | < 0.001 |
membrane | 2.306958 | 25 | 18.8 | 0.005 |
microtubule plus-end | 2.297019 | 3 | 2.256 | 0.005 |
cytosol | 1.228885 | 29 | 21.8 | 0.059 |
cytoplasmic mRNA processing body | 1.060323 | 3 | 2.256 | 0.087 |
C | ||||
GO-MF Term | Enrichment Score | Count | % | P-Value |
transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding | 3.752771 | 9 | 6.767 | < 0.001 |
protein binding | 2.747245 | 75 | 56.39 | 0.002 |
protein channel activity | 2.559552 | 3 | 2.256 | 0.003 |
transcription regulatory region sequence-specific DNA binding | 2.171926 | 4 | 3.008 | 0.007 |
sequence-specific DNA binding | 2.120902 | 10 | 7.519 | 0.008 |
RNA polymerase II core promoter proximal region sequence-specific DNA binding | 2.024814 | 8 | 6.015 | 0.009 |
chromatin binding | 1.812398 | 8 | 6.015 | 0.015 |
RNA polymerase II transcription coactivator activity | 1.602367 | 3 | 2.256 | 0.025 |
N6-methyladenosine-containing RNA binding | 1.341641 | 2 | 1.504 | 0.046 |
protein kinase activity | 1.042052 | 6 | 4.511 | 0.091 |
D | ||||
KEGG pathway | Enrichment Score | Count | % | P-Value |
PI3K-Akt signaling pathway | 1.809894 | 7 | 5.263 | 0.015 |
Oocyte meiosis | 1.553469 | 4 | 3.008 | 0.028 |
Platelet activation | 1.379399 | 4 | 3.008 | 0.042 |
Insulin signaling pathway | 1.315081 | 4 | 3.008 | 0.048 |
Hippo signaling pathway | 1.219786 | 4 | 3.008 | 0.06 |
Purine metabolism | 1.062637 | 4 | 3.008 | 0.087 |
ErbB signaling pathway | 1.024741 | 3 | 2.256 | 0.094 |
Expression of MALAT1, LINC00943 and LINC00261 is higher in tumour tissues
MALAT1 and LINC00943 are independent risk factors for the prognosis of cutaneous melanoma
A | ||||||
Number of cases, Total | Number of cases, Decased | Median Months, Overall | OR | 95%CI | p-value | |
MALAT1 | ||||||
with CNV deficiency | 82 | 53 | 34.23 | 0.714 | 0.524–0.975 | 0.034 |
without CNV deficiency | 454 | 243 | 63.53 | |||
LINC00943 | ||||||
with CNV deficiency | 54 | 34 | 55.59 | 0.671 | 0.465–0.969 | 0.033 |
without CNV deficiency | 482 | 262 | 61.05 | |||
LINC00261 | ||||||
with CNV deficiency | 23 | 16 | 17.03 | 0.612 | 0.356–1.053 | 0.076 |
without CNV deficiency | 513 | 280 | 61.05 | |||
B | ||||||
Number of cases, Total | Number of cases, Decased | Median Months, Overall | OR | 95%CI | p-value | |
MALAT1 | ||||||
with CNV deficiency | 84 | 69 | 15.52 | 0.691 | 0.528–0.906 | 0.007 |
without CNV deficiency | 448 | 331 | 27.09 | |||
LINC00943 | ||||||
with CNV deficiency | 55 | 45 | 21.37 | 0.704 | 0.511–0.971 | 0.033 |
without CNV deficiency | 477 | 355 | 24.82 | |||
LINC00261 | ||||||
with CNV deficiency | 23 | 19 | 13.50 | 0.842 | 0.516–1.374 | 0.491 |
without CNV deficiency | 509 | 381 | 25.02 |