PMID- 27827395 OWN - NLM STAT- MEDLINE DCOM- 20180516 LR - 20240326 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 6 DP - 2016 Nov 9 TI - Death receptor 5 (DR5) and a 5-gene apoptotic biomarker panel with significant differential diagnostic potential in colorectal cancer. PG - 36532 LID - 10.1038/srep36532 [doi] LID - 36532 AB - High expression of Inhibitor of apoptosis proteins (IAPs) has been related to colorectal cancer (CRC) progression, resistance to treatment and poor prognosis. TRAIL (TNF-related apoptosis-inducing ligand) through its receptors DR4 (TRAIL-R1) and DR5 (TRAIL-R2) can selectively induce cancer cell apoptosis. The mRNA expression of DR4, DR5, c-IAP1, c-IAP2, XIAP and BIRC5/Survivin genes was examined in 100 paired (cancerous-normal) colorectal tissue specimens by real-time PCR, 50 of which were KRAS wild-type and 50 KRAS-mutant. DR5, XIAP and BIRC5/Survivin genes are significantly up-regulated (p < 0.0001, p = 0.012 and p = 0.0003, respectively), whereas c-IAP1 and c-IAP2 genes are significantly down-regulated at mRNA and protein levels in CRC (p < 0.0001 for both). ROC analyses showed that DR5, cIAP1 and cIAP2 expression has discriminatory value between CRC and normal tissue (AUC = 0.700, p < 0.0001 for DR5; AUC = 0.628, p = 0.011 for cIAP1; AUC = 0.673, p < 0.0001 for cIAP2). Combinatorial ROC analysis revealed the marginally fair discriminatory value of 5 genes as a panel (AUC = 0.685, p < 0.0001). Kaplan-Meier survival curves revealed significant association of cIAP2 down-regulation in CRC with lower overall survival probability of CRC patients (p = 0.0098). DR5, BIRC5/Survivin, XIAP, c-IAP1 and c-IAP2 mRNA expression are significantly deregulated in CRC and could provide a panel of markers with significant discriminatory value between CRC and normal colorectal tissue. FAU - Devetzi, Marina AU - Devetzi M AD - Laboratory of Signal Mediated Gene Expression, Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, Athens, Greece. FAU - Kosmidou, Vivian AU - Kosmidou V AD - Laboratory of Signal Mediated Gene Expression, Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, Athens, Greece. FAU - Vlassi, Margarita AU - Vlassi M AD - Laboratory of Signal Mediated Gene Expression, Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, Athens, Greece. FAU - Perysinakis, Iraklis AU - Perysinakis I AD - 3rd Department of Surgery, General Hospital of Athens "G. Gennimatas", Athens, Greece. FAU - Aggeli, Chrysanthi AU - Aggeli C AD - 3rd Department of Surgery, General Hospital of Athens "G. Gennimatas", Athens, Greece. FAU - Choreftaki, Theodosia AU - Choreftaki T AD - Department of Pathology, General Hospital of Athens "G. Gennimatas", Athens, Greece. FAU - Zografos, Georgios N AU - Zografos GN AD - 3rd Department of Surgery, General Hospital of Athens "G. Gennimatas", Athens, Greece. FAU - Pintzas, Alexander AU - Pintzas A AD - Laboratory of Signal Mediated Gene Expression, Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, Athens, Greece. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20161109 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (BIRC5 protein, human) RN - 0 (Biomarkers, Tumor) RN - 0 (Inhibitor of Apoptosis Proteins) RN - 0 (RNA, Messenger) RN - 0 (Receptors, TNF-Related Apoptosis-Inducing Ligand) RN - 0 (Survivin) RN - 0 (TNFRSF10B protein, human) RN - 0 (X-Linked Inhibitor of Apoptosis Protein) RN - 0 (XIAP protein, human) SB - IM MH - Apoptosis/*genetics MH - Biomarkers, Tumor/*genetics MH - Colorectal Neoplasms/*diagnosis/genetics/metabolism MH - Down-Regulation MH - Gene Expression Profiling MH - Humans MH - Inhibitor of Apoptosis Proteins/metabolism MH - RNA, Messenger/genetics MH - Receptors, TNF-Related Apoptosis-Inducing Ligand/genetics/*metabolism MH - Survivin MH - Up-Regulation MH - X-Linked Inhibitor of Apoptosis Protein/metabolism PMC - PMC5101514 EDAT- 2016/11/09 06:00 MHDA- 2018/05/17 06:00 PMCR- 2016/11/09 CRDT- 2016/11/10 06:00 PHST- 2016/02/18 00:00 [received] PHST- 2016/10/13 00:00 [accepted] PHST- 2016/11/10 06:00 [entrez] PHST- 2016/11/09 06:00 [pubmed] PHST- 2018/05/17 06:00 [medline] PHST- 2016/11/09 00:00 [pmc-release] AID - srep36532 [pii] AID - 10.1038/srep36532 [doi] PST - epublish SO - Sci Rep. 2016 Nov 9;6:36532. doi: 10.1038/srep36532.