Noxaupregulation and 5-gene apoptotic biomarker panel in colorectal cancer

Background NOXA 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 andKRASgene mutations in CRC. Materials and methods Fresh 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-WhitneyUtest and receiver-operating characteristic (ROC) curve. Results NOXAwas found to be overexpressed in CRC tumours (P < .0001), even from early stage. Moreover,NOXA/MCL1mRNA expression was significantly elevated in tumour samples compared to normal pairs (P < .0001). ROC curve analysis showed that bothNOXAexpression and its combination withMcl1expression have fair discriminatory value between CRC and normal colorectal tissue. Combinatorial ROC analysis revealed the most significant discriminatory value ofNOXA, MCL1withcIAP1andcIAP2(AUC = 0.834,P < .0001) as a 5-gene panel of markers. Conclusion Noxa, Mcl1, DR5,cIAP1andcIAP2mRNA expressions are significantly deregulated in CRC and could provide a panel of markers with significant discriminatory value between CRC and normal colorectal tissue.

Automated summary

NOXA and MCL1 are overexpressed in CRC tumors and show significant differences compared to normal colorectal tissue. The mRNA expressions of NOXA, Mcl1, DR5, cIAP1, and cIAP2 are significantly deregulated in CRC, providing a panel of markers with significant discriminatory value between CRC and normal colorectal tissue.