Dataset Information

Correlations between TBL1XR1 and recurrence of colorectal cancer.

ABSTRACT: More than 25% localized CRC patients died from post-operative metastasis, and risk of metastasis varies among individuals due to the high heterogeneity of CRC. Therefore, figuring out potential biomarkers for disease recurrence would be invaluable to improve the follow-up efficiency and clinical treatment. Transducin (?)-like 1 X-linked receptor 1 (TBL1XR1) is a core component of the nuclear receptor corepressor complex, which functions as a repressive coregulatory factor for multiple transcription factors. The clinical significance of TBL1XR1 in CRC hasn't been fully elucidated. In this study, we investigated the expression of TBL1XR1 in primary CRC tissues and liver metastases from TNM stage IV CRC patients, and found that its expression in primary tumor tissues was an independent prognostic factor for tumor recurrence. Thus, we enrolled another cohort including TNM stage I-III patients to further evaluate the relationship between TBL1XR1 expression and disease recurrence. Accordingly, high TBL1XR1 expression indicates poor disease-free survival of stage I-III CRC patients. Furthermore, we confirmed the importance of ?-catenin signaling pathways in TBL1XR1-mediated CRC cell oncogenicity by clinical and cellular results. Our results emphasize the necessity of individual therapy decisions based on clinical biomarkers, especially for localized CRC patients who are not routinely treated with adjunctive chemotherapy.

SUBMITTER: Liu H

PROVIDER: S-EPMC5353619 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Correlations between TBL1XR1 and recurrence of colorectal cancer.

Liu Hongda H Xu Yunfei Y Zhang Qun Q Li Kangshuai K Wang Dawei D Li Shuo S Ning Shanglei S Yang Hui H Shi Weichen W Liu Zhaochen Z Chen Yuxin Y

Scientific reports 20170315

More than 25% localized CRC patients died from post-operative metastasis, and risk of metastasis varies among individuals due to the high heterogeneity of CRC. Therefore, figuring out potential biomarkers for disease recurrence would be invaluable to improve the follow-up efficiency and clinical treatment. Transducin (β)-like 1 X-linked receptor 1 (TBL1XR1) is a core component of the nuclear receptor corepressor complex, which functions as a repressive coregulatory factor for multiple transcript ...[more]

PMID: 28295012

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Project description:ImportanceSurveillance testing is performed after primary treatment for colorectal cancer (CRC), but it is unclear if the intensity of testing decreases time to detection of recurrence or affects patient survival.ObjectiveTo determine if intensity of posttreatment surveillance is associated with time to detection of CRC recurrence, rate of recurrence, resection for recurrence, or overall survival.Design, setting, and participantsA retrospective cohort study of patient data abstracted from the medical record as part of a Commission on Cancer Special Study merged with records from the National Cancer Database. A random sample of patients (n=8529) diagnosed with stage I, II, or III CRC treated at a Commission on Cancer-accredited facilities (2006-2007) with follow-up through December 31, 2014.ExposuresIntensity of imaging and carcinoembryonic antigen (CEA) surveillance testing derived empirically at the facility level using the observed to expected ratio for surveillance testing during a 3-year observation period.Main outcomes and measuresThe primary outcome was time to detection of CRC recurrence; secondary outcomes included rates of resection for recurrent disease and overall survival.ResultsA total of 8529 patients (49% men; median age, 67 years) at 1175 facilities underwent surveillance imaging and CEA testing within 3 years after their initial CRC treatment. The cohort was distributed by stage as follows: stage I, 25.0%; stage II, 35.2%; and stage III, 39.8%. Patients treated at high-intensity facilities-4188 patients (49.1%) for imaging and 4136 (48.5%) for CEA testing-underwent a mean of 2.9 (95% CI, 2.8-2.9) imaging scans and a mean of 4.3 (95% CI, 4.2-4.4) CEA tests. Patients treated at low-intensity facilities-4341 patients (50.8%) for imaging and 4393 (51.5%) for CEA testing-underwent a mean of 1.6 (95% CI, 1.6-1.7) imaging scans and a mean of 1.6 (95% CI, 1.6-1.7) CEA tests. Imaging and CEA surveillance intensity were not associated with a significant difference in time to detection of cancer recurrence. The median time to detection of recurrence was 15.1 months (IQR, 8.2-26.3) for patients treated at facilities with high-intensity imaging surveillance and 16.0 months (IQR, 7.9-27.2) with low-intensity imaging surveillance (difference, -0.95 months; 95% CI, -2.59 to 0.68; HR, 0.99; 95% CI, 0.90-1.09) and was 15.9 months (IQR, 8.5-27.5) for patients treated at facilities with high-intensity CEA testing and 15.3 months (IQR, 7.9-25.7) with low-intensity CEA testing (difference, 0.59 months; 95% CI, -1.33 to 2.51; HR, 1.00; 95% CI, 0.90-1.11). No significant difference existed in rates of resection for cancer recurrence (HR for imaging, 1.22; 95% CI, 0.99-1.51 and HR for CEA testing, 1.12; 95% CI, 0.91-1.39) or overall survival (HR for imaging, 1.01; 95% CI, 0.94-1.08 and HR for CEA testing, 0.96; 95% CI, 0.89-1.03) among patients treated at facilities with high- vs low-intensity imaging or CEA testing surveillance.Conclusions and relevanceAmong patients treated for stage I, II, or III CRC, there was no significant association between surveillance intensity and detection of recurrence.Trial registrationclinicaltrials.gov Identifier: NCT02217865.

Project description:BACKGROUND:Approximately one-third of those treated curatively for colorectal cancer (CRC) will experience recurrence. No evidence-based consensus exists on how best to follow patients after initial treatment to detect asymptomatic recurrence. Here, a new approach for simulating surveillance and recurrence among CRC survivors is outlined, and development and calibration of a simple model applying this approach is described. The model's ability to predict outcomes for a group of patients under a specified surveillance strategy is validated. METHODS:We developed an individual-based simulation model consisting of two interacting submodels: a continuous-time disease-progression submodel overlain by a discrete-time Markov submodel of surveillance and re-treatment. In the former, some patients develops recurrent disease which probabilistically progresses from detectability to unresectability, and which may produce early symptoms leading to detection independent of surveillance testing. In the latter submodel, patients undergo user-specified surveillance testing regimens. Parameters describing disease progression were preliminarily estimated through calibration to match five-year disease-free survival, overall survival at years 1-5, and proportion of recurring patients undergoing curative salvage surgery from one arm of a published randomized trial. The calibrated model was validated by examining its ability to predict these same outcomes for patients in a different arm of the same trial undergoing less aggressive surveillance. RESULTS:Calibrated parameter values were consistent with generally observed recurrence patterns. Sensitivity analysis suggested probability of curative salvage surgery was most influenced by sensitivity of carcinoembryonic antigen assay and of clinical interview/examination (i.e. scheduled provider visits). In validation, the model accurately predicted overall survival (59% predicted, 58% observed) and five-year disease-free survival (55% predicted, 53% observed), but was less accurate in predicting curative salvage surgery (10% predicted; 6% observed). CONCLUSIONS:Initial validation suggests the feasibility of this approach to modeling alternative surveillance regimens among CRC survivors. Further calibration to individual-level patient data could yield a model useful for predicting outcomes of specific surveillance strategies for risk-based subgroups or for individuals. This approach could be applied toward developing novel, tailored strategies for further clinical study. It has the potential to produce insights which will promote more effective surveillance-leading to higher cure rates for recurrent CRC.

Dataset Information

Correlations between TBL1XR1 and recurrence of colorectal cancer.

Publications

Correlations between TBL1XR1 and recurrence of colorectal cancer.

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