br protocadherin among case group and all controls The ROC
507 protocadherin-18) among case group 1 and all controls. The ROC score predicted a diagnosis of
508 endometrial cancer in patients diagnosed in ≤ 2 years from initial blood draw with an AUC of
509 0.8. Performance of this risk score for endometrial cancer cases diagnosed > 2 years to ≤ 5 years
510 exhibited an AUC of 0.64 and for cases diagnosed > 5 years following blood draw, an AUC of
Biomarkers Associated with
Tumor Heterogeneity in Prostate Cancer1,2
*Samsung Genome Institute, Samsung Medical Center, Seoul 06351, Republic of Korea; †Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul 06351, Republic of Korea; ‡Center for Health Promotion, Samsung Medical Center, Seoul, Republic of Korea; §Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Republic of Korea
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 M3814 (nedisertib) 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.
In many industrialized nations, prostate adenocarcinoma is one of the most common malignant diseases in men . Prostate cancer (PC) is considered clinically heterogeneous. Some prostate cancers are indolent and localized, while others are aggressive and easily spread to other parts of the body. Therefore, it is necessary to understand key features related to tumor progression and invasiveness. Many cases of prostate cancer are multifocal; most radical prostatectomy specimens harbor morphologically and clonally distinct tumor foci [2–4]. Studies of metastatic tumors from primary PC have suggested that all of those tumors evolved from one clone, as they share a significant portion of genetic alterations [5,6]. The characteristics and diversity of a clone may explain the aggressiveness of prostate cancer.
Address all correspondence to: Je-Gun Joung, PhD, Samsung Genome Institute, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea. or Jeongyun Jeong, MD, PhD, Center for Health Promotion, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Republic of Korea. E-mails: [email protected], [email protected]
1 Grant support: The study was supported in part by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2017R1D1A1B03034779).
2 Disclosure of potential conflicts of interest: There are no potential conflicts of interest to disclose. 3 These authors contributed equally to this work.
© 2018 The Authors. Published by Elsevier Inc. on behalf of Neoplasia Press, Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
44 Tumor Heterogeneity in Prostate Cancer Yun et al. Translational Oncology Vol. 12, No. 1, 2019
Therefore, it is important to perform a comprehensive genomic and transcriptomic characterization of the primary cancer lesion to understand the biology of the tumor and the factors associated with tumor progression. However, major factors that lead to tumor heterogeneity during prostate cancer progression are still not clear. Recently, next-generation sequencing provided a molecular portrait of genomic alterations. Furthermore, intratumor heterogeneity (ITH) has been inferred by clonality analysis . In various types of cancer, the characterization of clonal heterogeneity may provide useful information for predicting patient prognosis and treatment response.