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Published on: March 14, 2019
High Expression of MRE11A Is Associated with Shorter Survival and a Higher Risk of Death in CRC Patients
Daniel de Barcellos Azambuja1,2, Helena de Castro E Gloria1, Gabriel E Silva Montenegro1
1Laboratório de Genética Toxicológica, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre 90050-170, RS, Brazil.
Background:
Homologous recombination repair (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 of this mechanism is a frequent event in tumorigenesis. Therapies that exploit defects in HR have been explored essentially in breast, ovarian, pancreatic, 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 key HR components and mismatch repair (MMR) status, which correlated with clinicopathological features, progression-free survival, and overall survival (OS).
Results:
Enhanced expression of MRE11 homolog (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 the worst prognosis. 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 of 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.
Insights
High MRE11A expression in colorectal cancer (CRC) correlates with advanced tumors and poorer survival. Monitoring MRE11A may identify CRC patients for targeted therapies, improving outcomes.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Homologous recombination repair (HR) is crucial for DNA repair, and its deficiency is common in cancer.
- HR-deficient cancer therapies are established for several cancers but underutilized in colorectal cancer (CRC).
- CRC is a leading cause of cancer mortality worldwide, highlighting the need for novel therapeutic strategies.
Purpose of the Study:
- To investigate the role of homologous recombination repair (HR) gene expression in colorectal cancer (CRC).
- To assess the correlation between HR gene expression, clinicopathological features, and patient survival in CRC.
- To evaluate MRE11A as a potential biomarker for CRC prognosis and therapeutic selection.
Main Methods:
- Gene expression analysis of key HR components was performed on tumor and healthy tissues from 63 CRC patients.
- Mismatch repair (MMR) status was assessed.
- Correlations between gene expression, MMR status, clinicopathological features, progression-free survival, and overall survival (OS) were analyzed.
Main Results:
- MRE11A, a key HR resection gene, is significantly overexpressed in CRC, particularly in advanced T3-T4 tumors.
- High MRE11A expression is prevalent in right-sided CRC, a subtype with a worse prognosis.
- Elevated MRE11A transcript levels are linked to a 16.7-month shorter OS and a 3.5-fold increased risk of death.
Conclusions:
- MRE11A overexpression is a significant prognostic marker in colorectal cancer (CRC).
- MRE11A expression levels can predict patient outcomes and identify individuals for HR-deficient cancer therapies.
- Targeting MRE11A or utilizing it as a biomarker could enhance CRC treatment strategies.
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