TY - JOUR
T1 - Biomarkers Associated with Tumor Heterogeneity in Prostate Cancer
AU - Yun, Jae Won
AU - Lee, Soomin
AU - Ryu, Daeun
AU - Park, Semi
AU - Park, Woong Yang
AU - Joung, Je Gun
AU - Jeong, Jeongyun
N1 - Publisher Copyright:
© 2018 The Authors
PY - 2019/1
Y1 - 2019/1
N2 - BACKGROUND: Prostate cancers exhibit intratumor heterogeneity (ITH), like other cancer types. The ITH may affect diverse phenotypes such as treatment response, drug resistance, and clinical outcomes. It is crucial to consider ITH to understand tumorigenesis. METHODS: Genomic and transcriptomic profiles of prostate cancer patients were investigated to determine which markers are correlated with the degree of tumor heterogeneity. In addition, the correlation between the immune activity and clonality of tumors was examined. RESULTS: Tumor heterogeneity across all prostate cancer samples was variable. However, ITH events were dependent on genomic and clinical features. Interestingly, prostate-specific antigen score increased in tumors with multiple subclones, indicating high-grade tumor heterogeneity. On the other hand, CD8-positive T-cell activation decreased in highly heterogeneous tumors. Intriguingly, PTEN deletion was prominently enriched in high heterogeneity groups, with a strong association with heterozygous loss. Expression of major genes including PTEN, CDC42EP5, RNLS, GP2, NETO2, and AMPD3 was closely related to tumor heterogeneity in association with PTEN deletion. CONCLUSIONS: In prostate cancer, ITH, a potential factor affecting tumor progression, is associated with PTEN deletion and cytotoxic T cell inactivation.
AB - BACKGROUND: Prostate cancers exhibit intratumor heterogeneity (ITH), like other cancer types. The ITH may affect diverse phenotypes such as treatment response, drug resistance, and clinical outcomes. It is crucial to consider ITH to understand tumorigenesis. METHODS: Genomic and transcriptomic profiles of prostate cancer patients were investigated to determine which markers are correlated with the degree of tumor heterogeneity. In addition, the correlation between the immune activity and clonality of tumors was examined. RESULTS: Tumor heterogeneity across all prostate cancer samples was variable. However, ITH events were dependent on genomic and clinical features. Interestingly, prostate-specific antigen score increased in tumors with multiple subclones, indicating high-grade tumor heterogeneity. On the other hand, CD8-positive T-cell activation decreased in highly heterogeneous tumors. Intriguingly, PTEN deletion was prominently enriched in high heterogeneity groups, with a strong association with heterozygous loss. Expression of major genes including PTEN, CDC42EP5, RNLS, GP2, NETO2, and AMPD3 was closely related to tumor heterogeneity in association with PTEN deletion. CONCLUSIONS: In prostate cancer, ITH, a potential factor affecting tumor progression, is associated with PTEN deletion and cytotoxic T cell inactivation.
UR - https://www.scopus.com/pages/publications/85053856966
U2 - 10.1016/j.tranon.2018.09.003
DO - 10.1016/j.tranon.2018.09.003
M3 - Article
AN - SCOPUS:85053856966
SN - 1936-5233
VL - 12
SP - 43
EP - 48
JO - Translational Oncology
JF - Translational Oncology
IS - 1
ER -
