Overexpression of the MRE11-RAD50-NBS1 (MRN) complex in rectal cancer correlates with poor response to neoadjuvant radiotherapy and prognosis

Ho, Vincent; Chung, Liping; Singh, Amandeep; Lea, Vivienne; Abubakar, Askar; Lim, Stephanie; Ng, Wan; Lee, Mark T; Souza, Paul de; Shin, Joo‐Shik; Lee, Cheok Soon

doi:10.1186/s12885-018-4776-9

Cited by 63 publications

(61 citation statements)

References 43 publications

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“…This is a similar result to our finding that low postoperative RAD50 expression was associated with worse DFS and OS in early tumour stage and low-grade rectal cancer [58]. However, we found that with RAD50, in combination with other proteins, the MRN complex (MRE11/RAD50/NBS1) behaves quite differently from RAD50 alone [59]. Rectal cancer with a high expression of MRN complex proteins was associated with worse DFS and OS.…”

Section: Discussionsupporting

confidence: 90%

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Aberrant Expression of RAD52, Its Prognostic Impact in Rectal Cancer and Association with Poor Survival of Patients

Chung

Singh

et al. 2020

IJMS

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The DNA damage response enables cells to survive and maintain genome integrity. RAD52 is a DNA-binding protein involved in the homologous recombination in DNA repair, and is important for the maintenance of tumour genome integrity. We investigated possible correlations between RAD52 expression and cancer survival and response to preoperative radiotherapy. RAD52 expression was examined in tumour samples from 179 patients who underwent surgery for rectal cancer, including a sub-cohort of 40 patients who were treated with neoadjuvant therapy. A high score for RAD52 expression in the tumour centre was significantly associated with worse disease-free survival (DFS; p = 0.045). In contrast, reduced RAD52 expression in tumour centre samples from patients treated with neoadjuvant therapy (n = 40) significantly correlated with poor DFS (p = 0.025) and overall survival (OS; p = 0.048). Our results suggested that RAD52 may have clinical value as a prognostic marker of tumour response to neoadjuvant radiation and both disease-free status and overall survival in patients with rectal cancer.

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Section: Discussionsupporting

confidence: 90%

“…Immunohistochemical staining preparation was performed as described previously [59]. Prepared slides were incubated with a monoclonal anti-RAD52 primary antibody, clone 5H9 (1:500 dilutions, Life Span Bioscience #LS-B1709; Seattle, WA, USA) for 60 min at room temperature.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Aberrant Expression of RAD52, Its Prognostic Impact in Rectal Cancer and Association with Poor Survival of Patients

Chung

Singh

et al. 2020

IJMS

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“…This complex, in combination with ataxia telangiectasia mutated (ATM), coordinates the cellular detection and repair of DNA double-strand breaks (DSBs) (Altan et al, 2016). High expression of MRE11-RAD50-NBS1 is associated with poor prognosis and chemoresistance in GC (Altan et al, 2016) as well as poor response to neoadjuvant radiotherapy and prognosis in rectal cancer (Ho et al, 2018). The MRN complex is frequently not detected in low-grade epithelial ovarian cancer, suggesting high sensitivity to the PARP inhibitor (Brandt et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Expression of DNA Damage Response Markers in Early-Onset or Familial Gastric Cancers

Kim

Hwang

et al. 2019

Asian Pac J Cancer Prev

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Background:Early-onset or familial gastric cancer (GC) is known to have clinicopathologic profiles different from those of sporadic GC. We aimed to compare DNA damage response marker expression between early-onset or familial GC and sporadic GC.Methods:GC samples were obtained from patients who underwent gastrectomy for GC at Seoul National University Hospital. Immunohistochemical analyses of various DNA damage response markers, including BRCA1, BRCA2, MRE11, RAD51C, and γH2AX, were performed using 54 early-onset GC, 59 familial GC, and 337 sporadic GC tissue microarray samples. Correlations between marker expression and clinicopathologic features were evaluated by univariate and multivariate analyses, and overall survival was analyzed.Results:The rate of γH2AX positivity was significantly higher (p < 0.001) in early-onset or familial GC than in sporadic GC. In contrast, the rates of MRE11 negativity and RAD51C negativity were significantly higher in sporadic GC than in early-onset or familial GC. BRCA1 negativity was associated with decreased overall survival in sporadic GC (p = 0.002), and MRE11 negativity was associated with decreased overall survival in sporadic GC (p = 0.012).Conclusion:Our results show significant differences in DNA damage response marker expression between early-onset or familial GC and sporadic GC.

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“…[31][32][33][34] Lee et al recently reported obesity as an independent negative predictive factor for complete response to CCRT in rectal cancer. 35,36 As we known, tumor response could reflects early response to treatments and related to late response outcomes including recurrence and survival. Many studies also indicate that obesity is a common risk factor for cardiovascular disease and is an indicator of poor prognosis in multiple cancer types.…”

Section: Discussionmentioning

confidence: 99%

<p>PCSK1 Overexpression in Rectal Cancer Correlates with Poor Response to Preoperative Chemoradiotherapy and Prognosis</p>

Chou¹,

Chen²,

Lin³

et al. 2020

OTT

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Background: In a data mining search for potential therapeutic targets to improve the outcome of rectal cancer, we identified PCSK1 as the cell-cell signaling gene most significantly associated with poor response to concurrent chemoradiotherapy (CCRT). This study aims to investigate the prognostic value of PCSK1 expression in rectal cancer patients who underwent neoadjuvant CCRT. Methods: Endoscopic biopsy specimens from 172 rectal cancer patients receiving neoadjuvant CCRT followed by curative surgery were assessed immunohistochemically for PCSK1 expression, and H-scores were determined. Expression levels of PCSK1 were further analyzed for correlations with clinicopathologic features, tumor regression grade, metastasis-free survival, disease-specific survival, and recurrence-free survival. Results: PCKS1 overexpression was significantly associated with pretreatment tumor status (T3-4; p = 0.009), pretreatment nodal status (N1-2; p < 0.001), posttreatment tumor status (T3-4; p < 0.001), posttreatment nodal status (N1-2; p < 0.001), vascular invasion (p = 0.003), and perineurial invasion (p = 0.023). PCKS1 overexpression was also found to be significantly associated with a lower degree of tumor regression (p < 0.001). In the univariate analysis, PCSK1 overexpression was significantly associated with lower disease-specific survival, metastasis-free survival, and recurrence-free survival (p < 0.005). PCSK1 overexpression remained an independent prognostic factor of lower disease-specific survival (p = 0.003; hazard ratio, 5.478) in the multivariate analysis. Conclusion: Determination of PCSK1 overexpression may be useful for identifying rectal cancer patients at risk for a poor response and worse survival after CCRT.

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Overexpression of the MRE11-RAD50-NBS1 (MRN) complex in rectal cancer correlates with poor response to neoadjuvant radiotherapy and prognosis

Cited by 63 publications

References 43 publications

Aberrant Expression of RAD52, Its Prognostic Impact in Rectal Cancer and Association with Poor Survival of Patients

Aberrant Expression of RAD52, Its Prognostic Impact in Rectal Cancer and Association with Poor Survival of Patients

Expression of DNA Damage Response Markers in Early-Onset or Familial Gastric Cancers

<p>PCSK1 Overexpression in Rectal Cancer Correlates with Poor Response to Preoperative Chemoradiotherapy and Prognosis</p>

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