Expression of LDL receptor-related proteins (LRPs) in common solid malignancies correlates with patient survival

LDL receptor-related proteins (LRPs) are transmembrane receptors involved in endocytosis, cell-signaling, and trafficking of other cellular proteins. Considerable work has focused on LRPs in the fields of vascular biology and neurobiology. How these receptors affect cancer progression in humans remains largely unknown. Herein, we mined provisional data-bases in The Cancer Genome Atlas (TCGA) to compare expression of thirteen LRPs in ten common solid malignancies in patients. Our first goal was to determine the abundance of LRP mRNAs in each type of cancer. Our second goal was to determine whether expression of LRPs is associated with improved or worsened patient survival. In total, data from 4,629 patients were mined. In nine of ten cancers studied, the most abundantly expressed LRP was LRP1; however, a correlation between LRP1 mRNA expression and patient survival was observed only in bladder urothelial carcinoma. In this malignancy, high levels of LRP1 mRNA were associated with worsened patient survival. High levels of LDL receptor (LDLR) mRNA were associated with decreased patient survival in pancreatic adenocarcinoma. High levels of LRP10 mRNA were associated with decreased patient survival in hepatocellular carcinoma, lung adenocarcinoma, and pancreatic adenocarcinoma. LRP2 was the only LRP for which high levels of mRNA expression correlated with improved patient survival. This correlation was observed in renal clear cell carcinoma. Insights into LRP gene expression in human cancers and their effects on patient survival should guide future research

Survival disparities in Indigenous and non-Indigenous New Zealanders with colon cancer: the role of patient comorbidity, treatment and health service factors

Background Ethnic disparities in cancer survival have been documented in many populations and cancer types. The causes of these inequalities are not well understood but may include disease and patient characteristics, treatment differences and health service factors. Survival was compared in a cohort of Maori ( Indigenous) and non-Maori New Zealanders with colon cancer, and the contribution of demographics, disease characteristics, patient comorbidity, treatment and healthcare factors to survival disparities was assessed. Methods Maori patients diagnosed as having colon cancer between 1996 and 2003 were identified from the New Zealand Cancer Registry and compared with a randomly selected sample of non-Maori patients. Clinical and outcome data were obtained from medical records, pathology reports and the national mortality database. Cancer-specific survival was examined using Kaplane-Meier survival curves and Cox hazards modelling with multivariable adjustment. Results 301 Maori and 328 non-Maori patients with colon cancer were compared. Maori had a significantly poorer cancer survival than non-Maori ( hazard ratio (HR) 1.33, 95% CI 1.03 to 1.71) that was not explained by demographic or disease characteristics. The most important factors contributing to poorer survival in Maori were patient comorbidity and markers of healthcare access, each of which accounted for around a third of the survival disparity. The final model accounted for almost all the survival disparity between Maori and non-Maori patients ( HR 1.07, 95% CI 0.77 to 1.47). Conclusion Higher patient comorbidity and poorer access and quality of cancer care are both important explanations for worse survival in Maori compared with non-Maori New Zealanders with colon cancer

Preimplantation biopsy predicts delayed graft function, glomerular filtration rate and long-term graft survival of transplanted kidneys

Background The predictive value of preimplantation biopsies for long-term graft function is often limited by conflicting results. The aim of this study was to evaluate the influence of time-zero graft biopsy histological scores on early and late graft function, graft survival and patient survival, at different time points. Methods We retrospectively analyzed 284 preimplantation biopsies at a single center, in a cohort of recipients with grafts from live and deceased donors (standard and nonstandard), and their impact in posttransplant renal function after a mean follow-up of 7 years (range 1–16). Implantation biopsy score (IBS), a combination score derived from 4 histopathological aspects, was determined from each sample. The correlation with incidence of delayed graft function (DGF), creatinine clearance (1st, 3rd and 5th posttransplant year) and graft and patient survival at 1 and 5 years were evaluated. Results Preimplantation biopsies provided somewhat of a prognostic index of early function and outcome of the transplanted kidney in the short and long term. In the immediate posttransplantation period, the degree of arteriolosclerosis and interstitial fibrosis correlated better with the presence of DGF. IBS values between 4 and 6 were predictive of worst renal function at 1st and 3rd years posttransplant and 5-year graft survival. The most important histological finding, in effectively transplanted grafts, was the grade of interstitial fibrosis. Patient survival was not influenced by IBS. Conclusions Higher preimplantation biopsy scores predicted an increased risk of early graft losses, especially primary nonfunction. Graft survival (at 1st and 5th years after transplant) but not patient survival was predicted by IBS

Pancreatic cancer patient survival correlates with DNA methylation of pancreas development genes.

DNA methylation is an epigenetic mark associated with regulation of transcription and genome structure. These markers have been investigated in a variety of cancer settings for their utility in differentiating normal tissue from tumor tissue. Here, we examine the direct correlation between DNA methylation and patient survival. We find that changes in the DNA methylation of key pancreatic developmental genes are strongly associated with patient survival

Combined liver-kidney transplantation and the effect of preformed lymphocytotoxic antibodies

Thirty-eight sequentially placed liver and kidney allografts were evaluated with respect to patient and graft survival, and the influence of preformed lymphocytotoxic antibodies was analysed. The results suggest that the survival rate of combined liver and kidney transplantation is similar to the survival rate of liver transplantation alone. Sequentially placed kidney allografts may be protected from hyperacute rejection in the presence of donor specific lymphocytotoxic antibodies, but not in all instances. Both patient and kidney allograft survival was lower in positive crossmatch patients (33% and 17% respectively) than in negative crossmatch patients (78% and 75%). High levels of panel reactive antibodies (>10%) also appeared to have a deleterious effect on survival, although the majority of the patients who failed also had a positive crossmatch. Although preformed lymphocytotoxic antibodies are not an absolute contraindication to combined liver-kidney transplantation, they do appear to have a deleterious effect on long-term graft survival. However, more correlation with clinical parameters is needed. © 1994

Transfusion of red blood cells: the impact on short-term and long-term survival after coronary artery bypass grafting, a ten-year follow-up.

Transfusion of red blood cells (RBC) and other blood products in patients undergoing coronary artery bypass grafting (CABG) is associated with increased mortality and morbidity. We retrospectively analyzed data of patients who underwent an isolated coronary bypass graft operation between January 1998 and December 2007. Mean follow-up was 1696±1026 days, with exclusion of 122 patients lost to follow-up and 80 patients who received 10 units of RBC. Of the remaining patients, 8001 (76.7%) received no RBC, 1621 (15.2%) received 1–2 units of RBC, 593 (5.7%) received 3–5 units and 220 (2.1%) received 6–10 units. The number of transfused RBC was a predictor for early but not for late mortality. When compared to expected survival, survival of patients not receiving any blood product was better, while survival of patients receiving >3 units of RBC was worse. Transfusion of RBC is an independent, dose-dependent risk factor for early mortality after revascularization. Compared to expected survival, receiving no RBC improves patient long-term survival, whereas receiving three or more units of RBC significantly decreases patient survival

Predicting individual patient outcomes using prognostic models in economic evaluations

Objective When estimating incremental quality adjusted life years (QALYs) and costs in economic evaluations, prognostic models can be applied to predict survival times. However, these models do not themselves estimate whether the event, e.g. death or survival, would actually occur or not. When this projection is needed it is important to fully incorporate the uncertainty around it. Study Design and Setting This paper compares two methods for estimating patient specific outcomes. The average probability method uses the mean estimated proportion of survivors at a particular time point and assumes the patients with the longest survival times are the survivors. The second method uses probabilistic sensitivity analysis (PSA) to simulate individual patient outcomes. The two methods are illustrated using a prognostic model for estimating survival in the absence of liver transplantation. Results The mean survival, QALYs, costs and incremental cost-effectiveness ratio (ICER) were similar for the two methods. 95% confidence intervals were slightly wider for survival and QALY estimates and substantially wider for cost and ICER estimates when using PSA to estimate patient outcomes, thus capturing outcome uncertainty at the individual level. Conclusion PSA gives more realistic confidence intervals representing uncertainty than an average probability method and is the recommended method when estimating individual patient outcomes from prognostic models

"Suboptimal" kidney donors: The experience with tacrolimus-based immunosuppression

Female, pediatric, and older donors have been associated with inferior graft survival after renal transplantation. We analyzed these three subgroups in 397 patients receiving tacrolimus-based immunosuppression. There were no differences in recipient age, incidence of retransplantation, or percentage of sensitized patients. Female donors, compared with male donors, were associated with comparable 1- and 3-year patient survival rates (96% and 93% vs. 95% and 92%, respectively) and comparable 1- and 3-year graft survival rates (90% and 80% vs. 88% and 81%, respectively). Renal function was also similar. Recipients of pediatric en bloc kidneys, when compared with recipients of other cadaveric kidneys, also had comparable 1- and 3-year patient survival rates (94% and 94% vs. 95% and 91%, respectively) and comparable 1- and 3-year graft survival rates (84% and 84% vs. 89% and 79%, respectively). Renal function was better in recipients of en bloc kidneys, with a mean serum creatinine level of 1.4±1.8 mg/dl vs. 2.0±1.5 mg/dl (P=0.01). In contrast to the first two subgroups, donors over 60 years of age, when compared with donors under 60 years of age, were associated with worse 1- and 3-year patient survival rates (88% and 80% vs. 96% and 94%, respectively; P<0.03) and worse 1- and 3-year graft survival rates (74% and 62% vs. 91% and 83%, respectively; P<0.0001). Renal function was worse in the older donor group, with a serum creatinine level of 2.7±1.2 mg/ml vs. 1.9±1.5 mg/dl (P=0.01). We conclude that, under tacrolimus-based immunosuppression, kidneys from female or very young pediatric donors are not associated with adverse outcomes, whereas kidneys from donors over 60 years of age are associated with inferior outcomes