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Tumor Subtype-Specific Cancer–Testis Antigens as Potential Biomarkers and Immunotherapeutic Targets for Cancers

Jun Yao, Otavia L. Caballero, W.K. Alfred Yung, John N. Weinstein, Gregory J. Riggins, Robert L. Strausberg and Qi Zhao
Jun Yao
Departments of 1Neuro-Oncology and 2Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, The University of Texas—Houston Health Science Center, Houston, Texas; and 3Ludwig Collaborative Laboratory, Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
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Otavia L. Caballero
Departments of 1Neuro-Oncology and 2Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, The University of Texas—Houston Health Science Center, Houston, Texas; and 3Ludwig Collaborative Laboratory, Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
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W.K. Alfred Yung
Departments of 1Neuro-Oncology and 2Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, The University of Texas—Houston Health Science Center, Houston, Texas; and 3Ludwig Collaborative Laboratory, Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
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John N. Weinstein
Departments of 1Neuro-Oncology and 2Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, The University of Texas—Houston Health Science Center, Houston, Texas; and 3Ludwig Collaborative Laboratory, Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
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Gregory J. Riggins
Departments of 1Neuro-Oncology and 2Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, The University of Texas—Houston Health Science Center, Houston, Texas; and 3Ludwig Collaborative Laboratory, Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
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Robert L. Strausberg
Departments of 1Neuro-Oncology and 2Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, The University of Texas—Houston Health Science Center, Houston, Texas; and 3Ludwig Collaborative Laboratory, Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
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Qi Zhao
Departments of 1Neuro-Oncology and 2Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, The University of Texas—Houston Health Science Center, Houston, Texas; and 3Ludwig Collaborative Laboratory, Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
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DOI: 10.1158/2326-6066.CIR-13-0088 Published April 2014
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    Figure 1.

    CT gene expression frequency in human cancers. CT gene expression frequencies were calculated and genes having a >15% expression frequency in at least one tumor were plotted. Codes for cancer types: BRCA, breast; COAD, colon; GBM, glioblastoma; HNSC, head and neck; KIRC, kidney/renal clear cell carcinoma; LUAD, lung adenocarcinoma; LUSC, lung squamous cell carcinoma; OV, ovarian; SKCM, skin cutaneous melanoma; and UCEC, endometrial carcinoma.

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    Figure 2.

    Cancer subtype-specific CT gene expression. Gene expression heatmaps of top cancer subtype–specific CT genes were generated using TCGA RNAseq log2(RPKM) values for (A) breast cancer, (C) lung adenocarcinomas, (D) colorectal cancer, and (E) renal clear cell carcinomas. B, gene expression heatmap from a microarray dataset (NKI-295) generated by cluster and TreeView software using medium removal of normalized data to validate basal-specific CT genes found in TCGA (A). Similarly, the validation result from GSE26939 for TCGA lung adenocarcinoma is shown in C (right).

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    Figure 3.

    CT gene expression frequency in cancer subtypes. Cancer molecular subtypes were determined using consensus clustering and genes having a >30% overexpression frequency in at least one cancer subtype were plotted. For each cancer subtype, its percentage within the corresponding cancer is shown in parentheses.

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    Figure 4.

    Correlation of CT gene expression to DNA methylation. A, plot of the least median Pearson correlation coefficients between gene expression (using logged RNAseq RSEM values) and DNA methylation (using Met450 M values) for CT-X genes (red) and non-X CT genes (blue). B, scatter plots of CXorf61 and PRAME gene expression (logged RSEM values) versus DNA methylation (β values) in breast cancers and lung squamous cell carcinomas. Samples are labeled in colors to mark different cancer subtypes as shown in the legend. Infinium Met450 probes under study are marked on the figure, which can be used to locate exact chromosomal coordinates of the DNA methylation sites.

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    Figure 5.

    Prognostic value of CT genes in ccRCCs. A, percentages of CT genes and all genes found to be prognostic in human cancers. B, histogram of gene density along survival analysis Cox proportional hazards P values (in −log10) for 8 tumors all using 200 randomly picked samples. C, Kaplan–Meier analyses of patient outcome stratified by expression of SPANXC, C21orf99, and SSX1 genes in ccRCC. D, expression of top poor prognostic CT genes in ccRCC subtypes. Heatmap was generated using cluster and TreeView software after medium removal using RNAseq RSEM values.

Additional Files

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    Files in this Data Supplement:

    • Supplementary Figure Legend - PDF file - 61K
    • Supplementary Figure 1 - PDF file - 594K, Gene expression heatmaps for BRCA, KIRC, GBM, LUAD and UCEC. Survival curves for KIRC, LUAD and UCEC.
    • Supplementary Figure 1B - PDF file - 516K,Gene expression heatmaps for BRCA, KIRC, GBM, LUAD and UCEC. Survival curves for KIRC, LUAD and UCEC.
    • Supplementary Figure 2 - PDF file - 753K, Gene expression heatmap of top prognostic genes in KIRC.
    • Supplementary Table 1 - XLSX file - 14K, Supplemental Table S1. CT genes used in this study.
    • Supplementary Table 7 - XLSX file - 14K, Supplemental Table 7: P values in expression association tests for frequently expressed CTs.
    • Supplementary Table 3 - XLSX file - 22K, Supplemental Table S3. Estimated overexpression frequencies of CT genes in human cancers.
    • Supplementary Table 2 - PDF file - 13K, Supplemental Table S2. List of TCGA tumors and sample numbers used in this study.
    • Supplementary Table 5 - XLSX file - 41K, Supplemental Table S5. Correlation coefficient of CT gene expression and DNA methylation in cancers
    • Supplementary Table 4 - XLSX file - 34K, Supplemental Table S4. Estimated overexpression frequencies of CT genes in human cancer subtypes.
    • Supplementary Table 6 - XLSX file - 29K, Supplemental Table S6. List of Coxph Regression P values of CT genes in eight cancer types.
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Cancer Immunology Research: 2 (4)
April 2014
Volume 2, Issue 4
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Tumor Subtype-Specific Cancer–Testis Antigens as Potential Biomarkers and Immunotherapeutic Targets for Cancers
Jun Yao, Otavia L. Caballero, W.K. Alfred Yung, John N. Weinstein, Gregory J. Riggins, Robert L. Strausberg and Qi Zhao
Cancer Immunol Res April 1 2014 (2) (4) 371-379; DOI: 10.1158/2326-6066.CIR-13-0088

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Tumor Subtype-Specific Cancer–Testis Antigens as Potential Biomarkers and Immunotherapeutic Targets for Cancers
Jun Yao, Otavia L. Caballero, W.K. Alfred Yung, John N. Weinstein, Gregory J. Riggins, Robert L. Strausberg and Qi Zhao
Cancer Immunol Res April 1 2014 (2) (4) 371-379; DOI: 10.1158/2326-6066.CIR-13-0088
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