Comprehensive expression analysis of TNF-related apoptosis-inducing ligand and its receptors in colorectal cancer: Correlation with MAPK alterations and clinicopathological associations
| Autor: | Stratigoula Sakellariou, Ilenia Chatziandreou, Georgios E. Theodoropoulos, Penelope Korkolopoulou, Efstratios Patsouris, Nikolaos V. Michalopoulos, Angelica A. Saetta, Spyridon Tsikalakis |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Adult
Male 0301 basic medicine Neuroblastoma RAS viral oncogene homolog MAPK/ERK pathway MAP Kinase Signaling System Colorectal cancer medicine.medical_treatment Adenocarcinoma Biology medicine.disease_cause Pathology and Forensic Medicine Targeted therapy TNF-Related Apoptosis-Inducing Ligand 03 medical and health sciences 0302 clinical medicine Biomarkers Tumor medicine Humans Decoy receptors Receptor Aged Retrospective Studies Aged 80 and over Cell Biology Middle Aged medicine.disease Receptors TNF-Related Apoptosis-Inducing Ligand 030104 developmental biology Apoptosis 030220 oncology & carcinogenesis Mutation Cancer research Female KRAS Colorectal Neoplasms Transcriptome |
| Zdroj: | Pathology - Research and Practice. 214:826-834 |
| ISSN: | 0344-0338 |
| DOI: | 10.1016/j.prp.2018.04.019 |
| Popis: | TNF-related, apoptosis-inducing ligand (TRAIL) apoptotic pathway constitutes a promising therapeutic target due to high selectivity and low toxicity of TRAIL targeting agents when administered in combination therapies. 106 colorectal cancers were examined for: relative mRNA expression of TRAIL pathway genes, decoy receptors TRAIL-R3 and TRAIL-R4 promoter methylation and the presence of KRAS, NRAS, BRAF mutations. Elevated mRNA levels were observed in 26%, 15%, 13%, 12% and 10% of the cases for TRAIL-R4, TRAIL-R3, TRAIL-R2, TRAIL-R1 and TRAIL genes respectively. Reduced mRNA levels were detected in 77%, 65%, 64%, 60% and 37% of the cases for TRAIL, TRAIL-R2, TRAIL-R3, TRAIL-R1 and TRAIL-R4 genes respectively. TRAIL-R3 and TRAIL-R4 promoter methylation was detected in 55% and 16% of the analysed samples respectively. TRAIL-R1, TRAIL-R2 elevated relative mRNA levels inversely correlated with tumor stage (p = .036, p = .048). Strong linear correlations of TRAIL receptors' mRNA levels were found: TRAIL-R1/TRAIL-R2 (R = 0.653, p .001), TRAIL-R2/TRAIL-R3 (R = 0.573, p .001). Finally, relative expression of TRAIL was correlated with KRAS, BRAF and NRAS mutation status, defining an inverse correlation between increased TRAIL expression and the absence of mutations in Mitogen-activated protein kinase (MAPK) pathway. In conclusion, simultaneous analysis of TRAIL pathway membrane components, pointed towards a significant deregulation of mRNA expression in colorectal tumours. Death receptor overexpression was an indicator of a less aggressive phenotype. The multiple expression patterns of TRAIL pathway components in colorectal tumours underscore the importance of patient selection in order to achieve maximum efficiency with TRAIL targeted therapy. |
| Databáze: | OpenAIRE |
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