Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/26487
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dc.contributor.authorScarpa, Joseph R-
dc.contributor.authorDiNatale, Renzo G-
dc.contributor.authorMano, Roy-
dc.contributor.authorSilagy, Andrew W-
dc.contributor.authorKuo, Fengshen-
dc.contributor.authorIrie, Takeshi-
dc.contributor.authorMcCormick, Patrick J-
dc.contributor.authorFischer, Gregory W-
dc.contributor.authorHakimi, A Ari-
dc.contributor.authorMincer, Joshua S-
dc.date2020-12-14-
dc.date.accessioned2021-05-17T05:47:23Z-
dc.date.available2021-05-17T05:47:23Z-
dc.date.issued2021-02-15-
dc.identifier.citationCancer Research 2021; 81(4): 1101-1110en
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/26487-
dc.description.abstractWhile opioids constitute the major component of perioperative analgesic regimens for surgery in general, a variety of evidence points to an association between perioperative opioid exposure and longer term oncologic outcomes. The mechanistic details underlying these effects are not well understood. In this study, we focused on clear cell renal cell carcinoma (ccRCC) and utilized RNA sequencing and outcome data from both The Cancer Genome Atlas, as well as a local patient cohort to identify survival-associated gene coexpression networks. We then projected drug-induced transcriptional profiles from in vitro cancer cells to predict drug effects on these networks and recurrence-free, cancer-specific, and overall survival. The opioid receptor agonist, leu-enkephalin, was predicted to have antisurvival effects in ccRCC, primarily through Th2 immune- and NRF2-dependent macrophage networks. Conversely, the antagonist, naloxone, was predicted to have prosurvival effects, primarily through angiogenesis, fatty acid metabolism, and hemopoesis pathways. Eight coexpression networks associated with survival endpoints in ccRCC were identified, and master regulators of the transition from the normal to disease state were inferred, a number of which are linked to opioid pathways. These results are the first to suggest a mechanism for opioid effects on cancer outcomes through modulation of survival-associated coexpression networks. While we focus on ccRCC, this methodology may be employed to predict opioid effects on other cancer types and to personalize analgesic regimens in patients with cancer for optimal outcomes. SIGNIFICANCE: This study suggests a possible molecular mechanism for opioid effects on cancer outcomes generally, with implications for personalization of analgesic regimens.en
dc.language.isoeng
dc.titleIdentifying Clear Cell Renal Cell Carcinoma Coexpression Networks Associated with Opioid Signaling and Survival.en
dc.typeJournal Articleen
dc.identifier.journaltitleCancer Researchen
dc.identifier.affiliationDepartment of Anesthesiology, Weill Cornell Medicine, New York, New York..en
dc.identifier.affiliationDepartment of Anesthesiology and Critical Care Medicine, Memorial Sloan Kettering Cancer Center, New York, New York..en
dc.identifier.affiliationUrology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York..en
dc.identifier.affiliationUrology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New Yorken
dc.identifier.affiliationDepartment of Urology, Tel-Aviv Sourasky Medical Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv Yafo, Israel..en
dc.identifier.affiliationSurgery (University of Melbourne)en
dc.identifier.affiliationDepartment of Anesthesiology, Weill Cornell Medicine, New York, New Yorken
dc.identifier.doi10.1158/0008-5472.CAN-20-1852en
dc.type.contentTexten
dc.identifier.orcid0000-0003-1797-2896en
dc.identifier.orcid0000-0002-0456-1978en
dc.identifier.orcid0000-0002-7062-2409en
dc.identifier.orcid0000-0002-2482-3154en
dc.identifier.pubmedid33318038
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