Clinical Research Papers:
Six stroma-based RNA markers diagnostic for prostate cancer in European-Americans validated at the RNA and protein levels in patients in China
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Jianguo Zhu1,2,*, Cong Pan1,*, Jun Jiang3,*, Mingsen Deng1,*, Hengjun Gao4, Bozhao Men5, Michael McClelland5, Dan Mercola6, Wei-De Zhong7 and Zhenyu Jia1,8,9
1 Guizhou Provincial Key Laboratory of Computational Nano-Material Science, Guizhou Normal College, Guiyang, China
2 Department of Urology, Guizhou Provincial People’s Hospital, Guizhou, China
3 Department of Chemical Physics, University of Science and Technology of China, Hefei, China
4 National Engineering Center for Biochip at Shanghai, Shanghai, China
5 Department of Microbiology and Molecular Genetics, University of California, Irvine, Irvine, CA, USA
6 Department of Pathology and Laboratory Medicine, University of California, Irvine, Irvine, CA, USA
7 Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, Guangzhou Medical University, Guangzhou, China
8 Department of Statistics, The University of Akron, Akron, OH, USA
9 Department of Family and Community Medicine, Northeast Ohio Medical University, Rootstown, OH, USA
* These authors are Co-first authors
Zhenyu Jia, email:
Weide Zhong, email:
Keywords: prostate cancer, microenvironment, stroma, diagnosis, race
Received: February 04, 2015 Accepted: May 31, 2015 Published: June 19, 2015
We previously analyzed human prostate tissue containing stroma near to tumor and from cancer-negative tissues of volunteers. Over 100 candidate gene expression differences were identified and used to develop a classifier that could detect nearby tumor with an accuracy of 97% (sensitivity = 98% and specificity = 88%) based on 364 independent test cases from primarily European American cases. These stroma-based gene signatures have the potential to identify cancer patients among those with negative biopsies. In this study, we used prostate tissues from Chinese cases to validate six of these markers (CAV1, COL4A2, HSPB1, ITGB3, MAP1A and MCAM). In validation by real-time PCR, four genes (COL4A2, HSPB1, ITGB3, and MAP1A) demonstrated significantly lower expression in tumor-adjacent stroma compared to normal stroma (p value ≤ 0.05). Next, we tested whether these expression differences could be extended to the protein level. In IHC assays, all six selected proteins showed lower expression in tumor-adjacent stroma compared to the normal stroma, of which COL4A2, HSPB1 and ITGB3 showed significant differences (p value ≤ 0.05). These results suggest that biomarkers for diagnosing prostate cancer based on tumor microenvironment may be applicable across multiple racial groups.
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