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High Expression of MRE11A, the Gene Involved in the Resection Step During Homologous Recombination, Is Associated with Shorter Survival and a Higher Risk of Death in CRC Patients
Azambuja, D.B.; e Gloria, H.C.; Montenegro, G.S.; Kalil, A.N.; Hoffmann, J.-S.; Leguisamo, N.M.; Saffi, J. High Expression of MRE11A Is Associated with Shorter Survival and a Higher Risk of Death in CRC Patients. Genes2023, 14, 1270.
Azambuja, D.B.; e Gloria, H.C.; Montenegro, G.S.; Kalil, A.N.; Hoffmann, J.-S.; Leguisamo, N.M.; Saffi, J. High Expression of MRE11A Is Associated with Shorter Survival and a Higher Risk of Death in CRC Patients. Genes 2023, 14, 1270.
Azambuja, D.B.; e Gloria, H.C.; Montenegro, G.S.; Kalil, A.N.; Hoffmann, J.-S.; Leguisamo, N.M.; Saffi, J. High Expression of MRE11A Is Associated with Shorter Survival and a Higher Risk of Death in CRC Patients. Genes2023, 14, 1270.
Azambuja, D.B.; e Gloria, H.C.; Montenegro, G.S.; Kalil, A.N.; Hoffmann, J.-S.; Leguisamo, N.M.; Saffi, J. High Expression of MRE11A Is Associated with Shorter Survival and a Higher Risk of Death in CRC Patients. Genes 2023, 14, 1270.
Abstract
Background: Homologous Recombination (HR) is the most accurate repair pathway for double-strand breaks and replication fork disruption that is capable of faithfully restoring the original nucleotide sequence of the broken DNA. The deficiency in this mechanism is a frequent event in tumorigenesis. Therapies that exploit defects in HR have been explored essentially in breast, ovarian, pancreas, and prostate cancers, but poorly in colorectal cancers (CRC) although CRC ranks second in mortality worldwide. Methods: Tumor specimens and matched healthy tissues from 63 patients with CRC were assessed for gene expression of HR key components and MMR status, which were correlated with clinicopathological features, progression-free survival, and overall survival (OS). Results: Enhanced expression of MRE11A, the gene encoding a key molecular actor for resection is significantly overexpressed in CRC, is associated with the occurrence of primary tumors particularly T3-T4 and is found in more than 90% of the right-side of CRC, the location with worst prognostic. Importantly, we also found that high MRE11A transcript abundance is associated with 16.7 months shorter OS and a 3.5 higher risk of death.
Conclusion: Monitoring MRE11 expression could be used both as a predictor of outcome and as a marker to select CRC patients for treatments thus far adapted for HR deficient cancers.
Medicine and Pharmacology, Oncology and Oncogenics
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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