BackgroundThe 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.MethodsSamples 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.ResultsIn 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.ConclusionsExpression 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.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4776-9) contains supplementary material, which is available to authorized users.
BackgroundProstate cancer (PCa) is the most common cancer in men in Western countries. In-vitro and in-vivo studies suggest that oxidative stress (OS) and antioxidants play a key role in the pathogenesis of chronic diseases including PCa, which is promoted by the production of reactive oxygen species and impaired antioxidant defense mechanisms. This study evaluates the association between OS and men with PCa.MethodsA literature search was carried out on Medline, PubMed, and ScienceDirect databases, as well as manual searches from inception up to August 2015 using the keywords “Oxidative stress” or “Reactive oxygen species” or “Lipid peroxidation” AND “Prostate cancer.” All studies including data on the measurement of OS biomarkers in PCa were included.ResultsTwenty-three case control studies were retrieved with sample sizes ranging from 15 to 3,613 (6,439 participants in total). Markers of OS were significantly higher in patients with PCa compared with control groups in 21 studies. Two self-controlled case studies comparing OS between PCa cells and non-PCa cells in tissue biopsies found OS to be statistically higher in PCa cancer cells. Results on markers of antioxidant capacity (superoxide dismutase, catalase, glutathione, glutathione reductase, glutathione peroxidase, uric acid, lutein, lycopene, beta carotein, vitamin A, vitamin C, vitamin E, and total antioxidants) were not completely consistent in their association with PCa.ConclusionsUpregulated OS profiles and impairment of antioxidant defense systems may play a role in men with PCa. To confirm these findings, robust clinical trials utilizing a personalized approach which monitors both OS and antioxidant markers during therapy are warranted.
BackgroundAberrant expression of DNA repair proteins is associated with poor survival in cancer patients. We investigated the combined expression of MRE11 and ATM as a predictive marker of response to radiotherapy in rectal cancer.MethodsMRE11 and ATM expression were examined in tumor samples from 262 rectal cancer patients who underwent surgery for rectal cancer, including a sub-cohort of 54 patients who were treated with neoadjuvant radiotherapy. The relationship between expression of the two-protein panel and tumor regression grade (TRG) was assessed by Mann–Whitney U test and receiver operating characteristics area under curve (ROC-AUC) analysis. The association between expression of the two-protein panel and clinicopathologic variables and survival was examined by Kaplan-Meier methods and Cox regression analysis.ResultsA high score for two-protein combined expression in the tumor center (TC) was significantly associated with worse disease-free survival (DFS) (P = 0.035) and overall survival (OS) (P = 0.003) in the whole cohort, and with DFS (P = 0.028) and OS (P = 0.024) in the neoadjuvant subgroup (n = 54). In multivariate analysis, the two-protein combination panel (HR = 2.178, 95% CI 1.115–4.256, P = 0.023) and perineural invasion (HR = 2.183, 95% CI 1.222–3.899, P = 0.008) were significantly associated with DFS. Using ROC-AUC analysis of good versus poor histological tumor response among patients treated preoperatively with radiotherapy, the average ROC-AUC was 0.745 for the combined panel, 0.618 for ATM alone, and 0.711 for MRE11 alone.ConclusionsThe MRE11/ATM two-protein panel developed in this study may have clinical value as a predictive marker of tumor response to neoadjuvant radiotherapy, and a prognostic marker for disease-free and overall survival.
This systematic review and meta-analysis comparing MICST to open CST suggests MICST is associated with decreased overall post-operative wound complication rates. Further prospective studies are needed to verify these findings.
Circulating tumour cells (CTCs) hold great potential as liquid biopsies to prognosticate disease and guide treatment in colorectal cancer. However, their emerging role in determining the molecular phenotype of tumour metastasis carries even more promising clinical use in the provision of comprehensive biomarker detection for targeted therapies and determination of drug resistance. The isolation of CTCs is technology dependent, and in the case of epithelial cell adhesion molecule-based platforms, the ability to detect cells that have undergone the epithelial to mesenchymal transition (EMT) is ineffective. CTCs displaying a mesenchymal phenotype are believed to have an increased metastatic potential. The rarity of CTCs provides another challenge in the enumeration of these cells. The future will likely involve the analysis of individual CTCs at any stage of the EMT in order to provide real-time phenotypic and molecular snapshots capable of tracking the dynamic evolution of tumour progression over time.
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