• Vivian Kosmidou, Margarita Vlassi, Kyriakos Anagiotos, Sofia Raftopoulou, Eirini Kalogerakou, Salomi Skarmalioraki, Chrysanthi Aggeli, Theodosia Choreftaki, George Zografos, and Alexander Pintzas.
• Laboratory of Signal Mediated Gene Expression, Institute of Chemical Biology, National Hellenic Research Foundation, Athens, Greece.
• Eur. J. Clin. Invest. 2021 Jan 1; 51 (1): e13353.

BackgroundNOXA and MCL1 are involved in the intrinsic pathway of apoptosis, where Noxa selectively binds to MCL1 and prevents it from inhibiting apoptosis. Both factors are considered as potential tumour biomarkers, while MCL1 has attracted interest as target in cancer. The purpose of this study was to investigate the expression of NOXA and MCL1 in 160 CRC tumour samples, to investigate their significance, also in combination with IAPs, DR5 expression and KRAS gene mutations in CRC.Materials And MethodsFresh frozen colorectal tissue was obtained from patients undergoing surgery for CRC. Real-time quantitative PCR was performed for the determination of mRNA expression levels. Protein expression was determined immunohistochemically. Differences in the mRNA expression profile were evaluated with the nonparametric Wilcoxon signed ranks test. Statistical analysis was performed with the use of Mann-Whitney U test and receiver-operating characteristic (ROC) curve.ResultsNOXA was found to be overexpressed in CRC tumours (P < .0001), even from early stage. Moreover, NOXA/MCL1 mRNA expression was significantly elevated in tumour samples compared to normal pairs (P < .0001). ROC curve analysis showed that both NOXA expression and its combination with Mcl1 expression have fair discriminatory value between CRC and normal colorectal tissue. Combinatorial ROC analysis revealed the most significant discriminatory value of NOXA, MCL1 with cIAP1 and cIAP2 (AUC = 0.834, P < .0001) as a 5-gene panel of markers.ConclusionNoxa, Mcl1, DR5, cIAP1 and cIAP2 mRNA expressions are significantly deregulated in CRC and could provide a panel of markers with significant discriminatory value between CRC and normal colorectal tissue.© 2020 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.

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