Abstract 3772: A multi-scale survey to assess the impact of inflammatory diseases of the abdominal cavity and prostate cancer severity
Authors: Shameer Khader , Yadav Kamlesh Kumar , Li Li , Yadav Shalini S. , Glicksberg Benjamin , Khan Irtaza , Johnson Kipp W. , Badgeley Marcus A. , Elaiho Cordelia , Readhead Ben , Kidd Brian A. , Kasarskis Andrew , Dudley Joel T. , Tewari Ashutosh K. 
Published: July 2017

Introduction and Objectives: Prostate cancer (PCa) is the most common cancer detected in men (181,000 annual cases), and nearly 26,000 American men die each year due to PCa and related complications. Reports have shown that PCa is more aggressive when its comorbid with inflammatory diseases. However, the correlations and risks attributed to inflammatory diseases of the abdominal cavity and oncophenotypes are not known.

Methods: To investigate how inflammatory pathways and PCa genes induce aggressive oncophenotypes in the setting of PCa, we have compiled a multiscale survey that includes data from surgical observations, inflammatory phenotypes, clinical registries, biomarkers and mouse models. We applied an integrative informatics approach with experimental validation to understand the associations between inflammatory diseases (e.g., Crohn's disease, ulcerative colitis, collagenous colitis, indeterminate colitis, ischemic colitis, diverticulitis, hernia, etc.) and PCa.

Results: We found distinct patterns of shared molecular features—gene sets, pathways, and networks—and comorbidities across inflammatory disease and PCa. For example, we found that diverticulitis tend to increase inflammation in the abdominal cavity and could potentially lead to aggressive prostate oncophenotypes. To test abdominal inflammation and PCa correlation, we induced inflammation in a mouse model of hiatus hernia, which resulted in an increase in the expression of the combined markers of inflammation and PCa (TGFB, TNFA, and IL6). Evaluation of pathology stage, Gleason scores and physical attributes of previous inflammation observed during robotic prostatectomy surgery also reveals trend towards aggressive tumor characteristics with an increase in inflammation. Gene-set overlap analyses showed that several inflammatory disease and prostate cancer genes share genetic modules.

Conclusion: Collectively, our findings provide the first set of computational, experimental and clinical evidence to recommend clinicians to evaluate the impact of inflammatory disease induced oncophenotypes in patients with PCa. Given that 1.3 million patients undergo prostate-specific antigen (PSA)-triggered invasive trans-rectal biopsy, the present findings in combination with PSA could facilitate the identification patient subset with aggressive cancer. Stratifying patients at risk for prostate cancer who are undergoing surgical interventions of abdominal cavity for inflammation diseases could also evaluate other non-surgical or therapeutic strategies.

Funding acknowledgements: AKT is supported by grants from Prostate Cancer Foundation and Deane Prostate Health.

JT is supported by grants from National Cancer Institute NCI-U54-CA189201-02, National Center for Advancing Translational Sciences NCATS-UL1TR000067 and Clinical and Translational Science Award (CTSA).

Note: This abstract was not presented at the meeting.

Citation Format: Khader Shameer, Kamlesh Kumar Yadav, Li Li, Shalini S. Yadav, Benjamin Glicksberg, Irtaza Khan, Kipp W. Johnson, Marcus A. Badgeley, Cordelia Elaiho, Ben Readhead, Brian A. Kidd, Andrew Kasarskis, Joel T. Dudley, Ashutosh K. Tewari. A multi-scale survey to assess the impact of inflammatory diseases of the abdominal cavity and prostate cancer severity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3772. doi:10.1158/1538-7445.AM2017-3772