Offsetting Expression Profiles of Prognostic Markers in Prostate Tumor vs. Its Microenvironment

Zhenyu Jia; Jianguo Zhu; Yangjia Zhuo; Ruidong Li; Han Qu; Shibo Wang; Meiyue Wang; Jianming Lu; Jianming Lu; John M. Chater; Renyuan Ma; Renyuan Ma; Ze-zhen Liu; Zhiduan Cai; Yongding Wu; Funeng Jiang; Huichan He; Wei-De Zhong; Chin-Lee Wu

doi:10.3389/fonc.2019.00539

Frontiers in Oncology (Jun 2019)

Offsetting Expression Profiles of Prognostic Markers in Prostate Tumor vs. Its Microenvironment

Zhenyu Jia,
Jianguo Zhu,
Yangjia Zhuo,
Ruidong Li,
Han Qu,
Shibo Wang,
Meiyue Wang,
Jianming Lu,
Jianming Lu,
John M. Chater,
Renyuan Ma,
Renyuan Ma,
Ze-zhen Liu,
Zhiduan Cai,
Yongding Wu,
Funeng Jiang,
Huichan He,
Wei-De Zhong,
Chin-Lee Wu

Affiliations

Zhenyu Jia: Department of Botany and Plant Sciences, University of California, Riverside, Riverside, CA, United States
Jianguo Zhu: Department of Urology, Guizhou Provincial People's Hospital, Guangzhou, China
Yangjia Zhuo: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
Ruidong Li: Department of Botany and Plant Sciences, University of California, Riverside, Riverside, CA, United States
Han Qu: Department of Botany and Plant Sciences, University of California, Riverside, Riverside, CA, United States
Shibo Wang: Department of Botany and Plant Sciences, University of California, Riverside, Riverside, CA, United States
Meiyue Wang: Department of Botany and Plant Sciences, University of California, Riverside, Riverside, CA, United States
Jianming Lu: Department of Botany and Plant Sciences, University of California, Riverside, Riverside, CA, United States
Jianming Lu: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
John M. Chater: Department of Botany and Plant Sciences, University of California, Riverside, Riverside, CA, United States
Renyuan Ma: Department of Botany and Plant Sciences, University of California, Riverside, Riverside, CA, United States
Renyuan Ma: Department of Mathematics, Bowdoin College, Brunswick, ME, United States
Ze-zhen Liu: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
Zhiduan Cai: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
Yongding Wu: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
Funeng Jiang: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
Huichan He: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
Wei-De Zhong: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
Chin-Lee Wu: Department of Pathology and Urology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States

DOI: https://doi.org/10.3389/fonc.2019.00539
Journal volume & issue: Vol. 9

Abstract

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Diagnosis of the presence of tumors and subsequent prognosis based on tumor microenvironment becomes more clinically practical because tumor-adjacent tissues are easy to collect and they are more genetically homogeneous. The purpose of this study was to identify new prognostic markers in prostate stroma that are near the tumor. We have demonstrated the prognostic features of FGFR1, FRS2, S6K1, LDHB, MYPT1, and P-LDHA in prostate tumors using tissue microarrays (TMAs) which consist of 241 patient samples from Massachusetts General Hospital (MGH). In this study, we investigated these six markers in the tumor microenvironment using an Aperio Imagescope system in the same TMAs. The joint prognostic power of markers was further evaluated and classified using a new algorithm named Weighted Dichotomizing. The classifier was verified via rigorous 10-fold cross validation. Statistical analysis of the protein expression indicated that in tumor-adjacent stroma FGFR1 and MYPT1 were significantly correlated with patient outcomes and LDHB showed the outcome-association tendency. More interestingly, these correlations were completely opposite regarding tumor tissue as previously reported. The results suggest that prognostic testing should utilize either tumor-enriched tissue or stroma with distinct signature profiles rather than using mixture of both tissue types. The new classifier based on stroma tissue has potential value in the clinical management of prostate cancer patients.

Published in Frontiers in Oncology

ISSN: 2234-943X (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.frontiersin.org/journals/oncology/

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