Overexpression of the MRE11-RAD50-NBS1 (MRN) complex in rectal cancer correlates with poor response to neoadjuvant radiotherapy and prognosis
Abstract Background The MRE11/RAD50/NBS1 (MRN) complex plays an essential role in detecting and repairing double-stranded breaks, and thus the potential roles of MRE11, RAD50 and NBS1 proteins in the pathogenesis of various cancers is the subject of investigation. This study was aimed at assessing t...
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| Format: | Article |
| Language: | English |
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BMC
2018-09-01
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| Series: | BMC Cancer |
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| Online Access: | http://link.springer.com/article/10.1186/s12885-018-4776-9 |
| _version_ | 1818180114694799360 |
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| author | Vincent Ho Liping Chung Amandeep Singh Vivienne Lea Askar Abubakar Stephanie H. Lim Weng Ng Mark Lee Paul de Souza Joo-Shik Shin Cheok Soon Lee |
| author_facet | Vincent Ho Liping Chung Amandeep Singh Vivienne Lea Askar Abubakar Stephanie H. Lim Weng Ng Mark Lee Paul de Souza Joo-Shik Shin Cheok Soon Lee |
| author_sort | Vincent Ho |
| collection | DOAJ |
| description | Abstract Background The MRE11/RAD50/NBS1 (MRN) complex plays an essential role in detecting and repairing double-stranded breaks, and thus the potential roles of MRE11, RAD50 and NBS1 proteins in the pathogenesis of various cancers is the subject of investigation. This study was aimed at assessing the three-protein panel of MRN complex subunits as a potential radiosensitivity marker and evaluating the prognostic and clinicopathological implications of MRN expression in rectal cancer. Methods Samples from 265 rectal cancer patients treated with surgery and adjuvant chemoradiotherapy, including samples from 55 patients who were treated with neoadjuvant radiotherapy between 2000 and 2011, were analyzed. Expression of MRN complex proteins in tissue samples was determined by immunohistochemistry. Univariate and multivariate analyses were carried out to identify clinicopathological characteristics that are associated with the MRN three-protein panel expression in rectal cancer samples. Results In Kaplan–Meier survival analyses, we found that high level expression of MRN complex proteins in postoperative samples was associated with poor disease-free (p = 0.021) and overall (P = 0.002) survival. Interestingly, high MRN expression also correlated with poor disease-free (P = 0.047) and overall (P = 0.024) survival in the neoadjuvant radiotherapy subgroup. In multivariate analysis, combined MRN expression (hazard ratio = 2.114, 95% confidence interval 1.096–4.078, P = 0.026) and perineural invasion (hazard ratio = 2.160, 95% confidence interval 1.209–3.859, P = 0.009) were significantly associated with a worse disease-free survival. Conclusions Expression levels of MRN complex proteins significantly predict disease-free survival in rectal cancer patients, including those treated with neoadjuvant radiotherapy, and may have value in the management of these patients. |
| first_indexed | 2024-12-11T21:14:37Z |
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| id | doaj.art-5e214742cec648bfa017871cf3777701 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-11T21:14:37Z |
| publishDate | 2018-09-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-5e214742cec648bfa017871cf37777012022-12-22T00:50:37ZengBMCBMC Cancer1471-24072018-09-0118111110.1186/s12885-018-4776-9Overexpression of the MRE11-RAD50-NBS1 (MRN) complex in rectal cancer correlates with poor response to neoadjuvant radiotherapy and prognosisVincent Ho0Liping Chung1Amandeep Singh2Vivienne Lea3Askar Abubakar4Stephanie H. Lim5Weng Ng6Mark Lee7Paul de Souza8Joo-Shik Shin9Cheok Soon Lee10MBBS FRACP, School of Medicine, Western Sydney UniversityMBBS FRACP, School of Medicine, Western Sydney UniversityDepartment of Anatomical Pathology, Liverpool HospitalDepartment of Anatomical Pathology, Liverpool HospitalMBBS FRACP, School of Medicine, Western Sydney UniversityIngham Institute for Applied Medical ResearchDepartment of Medical Oncology, Liverpool HospitalDepartment of Radiation Oncology, Liverpool HospitalMBBS FRACP, School of Medicine, Western Sydney UniversityTissue Pathology and Diagnostic Oncology, Royal Prince Alfred HospitalMBBS FRACP, School of Medicine, Western Sydney UniversityAbstract Background The MRE11/RAD50/NBS1 (MRN) complex plays an essential role in detecting and repairing double-stranded breaks, and thus the potential roles of MRE11, RAD50 and NBS1 proteins in the pathogenesis of various cancers is the subject of investigation. This study was aimed at assessing the three-protein panel of MRN complex subunits as a potential radiosensitivity marker and evaluating the prognostic and clinicopathological implications of MRN expression in rectal cancer. Methods Samples from 265 rectal cancer patients treated with surgery and adjuvant chemoradiotherapy, including samples from 55 patients who were treated with neoadjuvant radiotherapy between 2000 and 2011, were analyzed. Expression of MRN complex proteins in tissue samples was determined by immunohistochemistry. Univariate and multivariate analyses were carried out to identify clinicopathological characteristics that are associated with the MRN three-protein panel expression in rectal cancer samples. Results In Kaplan–Meier survival analyses, we found that high level expression of MRN complex proteins in postoperative samples was associated with poor disease-free (p = 0.021) and overall (P = 0.002) survival. Interestingly, high MRN expression also correlated with poor disease-free (P = 0.047) and overall (P = 0.024) survival in the neoadjuvant radiotherapy subgroup. In multivariate analysis, combined MRN expression (hazard ratio = 2.114, 95% confidence interval 1.096–4.078, P = 0.026) and perineural invasion (hazard ratio = 2.160, 95% confidence interval 1.209–3.859, P = 0.009) were significantly associated with a worse disease-free survival. Conclusions Expression levels of MRN complex proteins significantly predict disease-free survival in rectal cancer patients, including those treated with neoadjuvant radiotherapy, and may have value in the management of these patients.http://link.springer.com/article/10.1186/s12885-018-4776-9DNA damage responseMRE11-RAD50-NBS1 complexRectal cancerPrognosisBiomarkersNeoadjuvant radiotherapy |
| spellingShingle | Vincent Ho Liping Chung Amandeep Singh Vivienne Lea Askar Abubakar Stephanie H. Lim Weng Ng Mark Lee Paul de Souza Joo-Shik Shin Cheok Soon Lee Overexpression of the MRE11-RAD50-NBS1 (MRN) complex in rectal cancer correlates with poor response to neoadjuvant radiotherapy and prognosis BMC Cancer DNA damage response MRE11-RAD50-NBS1 complex Rectal cancer Prognosis Biomarkers Neoadjuvant radiotherapy |
| title | Overexpression of the MRE11-RAD50-NBS1 (MRN) complex in rectal cancer correlates with poor response to neoadjuvant radiotherapy and prognosis |
| title_full | Overexpression of the MRE11-RAD50-NBS1 (MRN) complex in rectal cancer correlates with poor response to neoadjuvant radiotherapy and prognosis |
| title_fullStr | Overexpression of the MRE11-RAD50-NBS1 (MRN) complex in rectal cancer correlates with poor response to neoadjuvant radiotherapy and prognosis |
| title_full_unstemmed | Overexpression of the MRE11-RAD50-NBS1 (MRN) complex in rectal cancer correlates with poor response to neoadjuvant radiotherapy and prognosis |
| title_short | Overexpression of the MRE11-RAD50-NBS1 (MRN) complex in rectal cancer correlates with poor response to neoadjuvant radiotherapy and prognosis |
| title_sort | overexpression of the mre11 rad50 nbs1 mrn complex in rectal cancer correlates with poor response to neoadjuvant radiotherapy and prognosis |
| topic | DNA damage response MRE11-RAD50-NBS1 complex Rectal cancer Prognosis Biomarkers Neoadjuvant radiotherapy |
| url | http://link.springer.com/article/10.1186/s12885-018-4776-9 |
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