TY - JOUR
T1 - Tumor subtype-specific cancer-testis antigens as potential biomarkers and immunotherapeutic targets for cancers
AU - Yao, Jun
AU - Caballero, Otavia L.
AU - Yung, W. K.Alfred
AU - Weinstein, John N.
AU - Riggins, Gregory J.
AU - Strausberg, Robert L.
AU - Zhao, Qi
N1 - Funding Information:
W.K.A. Yung has received a research grant from Daiichi Sankyo, and honoraria from Actelion and serves as a consultant to Novartis and Merck. No potential conflicts of interest were disclosed by the other authors.
Funding Information:
This study is supported in part by the TCGA grant U24CA143883 from NCI/NIH, and funds from Ludwig Institute for Cancer Research. The costs ofpublication of this article were defrayed in partby the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Funding Information:
This study is supported in part by the TCGA grant U24CA143883 from NCI/ NIH, and funds from Ludwig Institute for Cancer Research.
Publisher Copyright:
© 2013 American Association for Cancer Research.
PY - 2014/4
Y1 - 2014/4
N2 - Cancer-testis (CT) antigens are potential targets for cancer immunotherapy because of their restricted expression in immune-privileged germ cells and various malignancies. Current application of CT-based immunotherapy has been focused on CT expression-rich tumors such as melanoma and lung cancers. In this study, we surveyed CT expression using The Cancer Genome Atlas (TCGA) datasets for ten common cancer types. We show that CT expression is specific and enriched within certain cancer molecular subtypes. For example, HORMAD1, CXorf61, ACTL8, and PRAME are highly enriched in the basal subtype of breast cancer; MAGE and CSAG are most frequently activated in the magnoid subtype of lung adenocarcinoma; and PRAME is highly upregulated in the ccB subtype of clear cell renal cell carcinoma. Analysis of CT gene expression and DNA methylation indicates that some CTs are regulated epigenetically, whereas others are controlled primarily by tissue- and subtype-specific transcription factors. Our results suggest that although for some CT expression is associated with patient outcome, not many are independent prognostic markers. Thus, CTs with shared expression pattern are heterogeneous molecules with distinct activation modes and functional properties in different cancers and cancer subtypes. These data suggest a cancer subtype-orientated application of CT antigen as biomarkers and immunotherapeutic targets.
AB - Cancer-testis (CT) antigens are potential targets for cancer immunotherapy because of their restricted expression in immune-privileged germ cells and various malignancies. Current application of CT-based immunotherapy has been focused on CT expression-rich tumors such as melanoma and lung cancers. In this study, we surveyed CT expression using The Cancer Genome Atlas (TCGA) datasets for ten common cancer types. We show that CT expression is specific and enriched within certain cancer molecular subtypes. For example, HORMAD1, CXorf61, ACTL8, and PRAME are highly enriched in the basal subtype of breast cancer; MAGE and CSAG are most frequently activated in the magnoid subtype of lung adenocarcinoma; and PRAME is highly upregulated in the ccB subtype of clear cell renal cell carcinoma. Analysis of CT gene expression and DNA methylation indicates that some CTs are regulated epigenetically, whereas others are controlled primarily by tissue- and subtype-specific transcription factors. Our results suggest that although for some CT expression is associated with patient outcome, not many are independent prognostic markers. Thus, CTs with shared expression pattern are heterogeneous molecules with distinct activation modes and functional properties in different cancers and cancer subtypes. These data suggest a cancer subtype-orientated application of CT antigen as biomarkers and immunotherapeutic targets.
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U2 - 10.1158/2326-6066.CIR-13-0088
DO - 10.1158/2326-6066.CIR-13-0088
M3 - Article
C2 - 24764584
AN - SCOPUS:84921435869
SN - 2326-6066
VL - 2
SP - 371
EP - 379
JO - Cancer Immunology Research
JF - Cancer Immunology Research
IS - 4
ER -