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BACKGROUND: Lung transplantation is the gold standard for a carefully selected patient population with end-stage lung disease. We sought to create a unique risk stratification model using only preoperative recipient data to predict one-year postoperative mortality during our pre-transplant assessment. METHODS: Data of lung transplant recipients at Houston Methodist Hospital (HMH) from 1/2009 to 12/2014 were extracted from the United Network for Organ Sharing (UNOS) database. Patients were randomly divided into development and validation cohorts. Cox proportional-hazards models were conducted. Variables associated with 1-year mortality post-transplant were assigned weights based on the beta coefficients, and risk scores were derived. Patients were stratified into low-, medium- and high-risk categories. Our model was validated using the validation dataset and data from other US transplant centers in the UNOS database RESULTS: We randomized 633 lung recipients from HMH into the development (n=317 patients) and validation cohort (n=316). One-year survival after transplant was significantly different among risk groups: 95% (low-risk), 84% (medium-risk), and 72% (high-risk) (p<0.001) with a C-statistic of 0.74. Patient survival in the validation cohort was also significantly different among risk groups (85%, 77% and 65%, respectively, p<0.001). Validation of the model with the UNOS dataset included 9,920 patients and found 1-year survival to be 91%, 86% and 82%, respectively (p < 0.001). CONCLUSIONS: Using only recipient data collected at the time of pre-listing evaluation, our simple scoring system has good discrimination power and can be a practical tool in the assessment and selection of potential lung transplant recipients.
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Detecting survival-associated biomarkers from heterogeneous populations
Abstract Detection of prognostic factors associated with patients’ survival outcome helps gain insights into a disease and guide treatment decisions. The rapid advancement of high-throughput technologies has yielded plentiful genomic biomarkers as candidate prognostic factors, but most are of limited use in clinical application. As the price of the technology drops over time, many genomic studies are conducted to explore a common scientific question in different cohorts to identify more reproducible and credible biomarkers. However, new challenges arise from heterogeneity in study populations and designs when jointly analyzing the multiple studies. For example, patients from different cohorts show different demographic characteristics and risk profiles. Existing high-dimensional variable selection methods for survival analysis, however, are restricted to single study analysis. We propose a novel Cox model based two-stage variable selection method called “Cox-TOTEM” to detect survival-associated biomarkers common in multiple genomic studies. Simulations showed our method greatly improved the sensitivity of variable selection as compared to the separate applications of existing methods to each study, especially when the signals are weak or when the studies are heterogeneous. An application of our method to TCGA transcriptomic data identified essential survival associated genes related to the common disease mechanism of five Pan-Gynecologic cancers.
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- Award ID(s):
- 2014971
- PAR ID:
- 10232645
- Date Published:
- Journal Name:
- Scientific Reports
- Volume:
- 11
- Issue:
- 1
- ISSN:
- 2045-2322
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1038/s41598-021-82332-y
