Genomic alterations of Tenascin C in highly aggressive prostate cancer: a meta-analysis
Prachi Mishra1,2, Michael A. Kiebish3, Jennifer Cullen1,2, Alagarsamy Srinivasan2, Aliyah Patterson4, Rangaprasad Sarangarajan3, Niven R. Narain3 and Albert Dobi1,2
1 Henry Jackson Foundation for Advancement of Military Medicine, Bethesda, MD, USA
2 Center for Prostate Disease Research, USU-Walter Reed Surgery, Bethesda, MD, USA
3 BERG LLC., Framingham, MA, USA
4 Division of Science and Mathematics, University of the District of Columbia, Washington DC, USA
Correspondence:
Prachi Mishra, email:
Correspondence:
Albert Dobi, email:
Keywords: prostate cancer; neuroendocrine subtype; Tenascin C; TCGA; biomarkers
Received: May 14, 2019 Accepted: July 17, 2019 Published: July 31, 2019
Abstract
Tenascin C (TNC), an extra-cellular matrix (ECM) family gene, is expressed in several cancer tissues of breast, lung, colon, and gastrointestinal tract leading to proliferation, migration, invasion, angiogenesis and metastasis, but its role in tumorigenesis of prostate cancer is poorly understood. We took a meta-analysis approach to characterize the alterations of TNC gene in prostate cancer using publicly available databases (cBioportal Version 2.2.0, http://www.cBioportal.org/index.do). The analysis identified TNC alterations (gene amplification) significantly in the neuroendocrine prostate cancer dataset (Trento/Broad/ Cornell, N = 114), which was further validated in other prostate cancer datasets, including The Cancer Genome Atlas (TCGA) prostate cancer (2015). In the TCGA prostate cancer dataset (N = 498), high TNC (alteration frequency, 36%) revealed a strong association with high diagnostic Gleason score. Genomic alterations of TNC was also significantly associated (P < 0.05) with expression level of genes from NOTCH, SOX and WNT family, implicating a link between TNC and poorly differentiated aggressive phenotype in NEPC. TCGA prostate adenocarcinoma cases with TNC alteration also demonstrated prominent decrease in disease-free survival (P = 0.0637). These findings indicate a possible association of TNC to the aggressive subtype of prostate cancer and warrant further functional studies to evident the involvement of TNC in prostate cancer progression.
