Three-dimensionally-printed anthropomorphic physical phantom for mammography and digital breast tomosynthesis with custom materials, lesions, and uniform quality control region,"
The association of MAPT (Tau) with various tauopathies and other neurological disorders has long been established. However, the role of microtubule-associated protein Tau (MAPT) expression in brain cancer is largely unknown. To determine whether MAPT expression is related to low-grade glioma (LGG) survival rates, RNASeq data representing samples from the Cancer Genome Atlas (TCGA) were assessed. Results revealed that high expression of the MAPT gene is very strongly associated with increased overall and disease-free survival in LGG but not in breast cancer or melanoma. No such association was apparent for either amyloid precursor protein or α-synuclein gene expression. The expression levels of particular apoptosis-and pro-proliferative-effector genes were consistent with the Tau-associated increased survival rates. It has been well established that the Tau protein plays a neurodegenerative role, and in this study we identified, for the first time, a potential cell apoptosis function that Tau may play in cancers of the central nervous system.
Overstimulation of pro-proliferative pathways and high level expression of pro-proliferative transcription factors (TFs) can lead to apoptosis. This is likely due to TF binding sites for pro-proliferative TFs common to pro-proliferative and pro-apoptosis-effector genes. Certain clinical datasets have indicated that molecular markers associated with higher proliferation rates lead to improved outcomes for patients with cancer. These observations have been extensively assessed on a general basis, however there has been little work dissecting feed-forward apoptosis signaling pathways that may represent specific distinctions between a pro-proliferative mechanism and a pro-apoptotic mechanism in samples from patients with cancer. Using The Cancer Genome Atlas datasets and bioinformatic approaches, the present study reports that higher FOS expression levels, along with higher FOS target apoptosis-effector gene expression, is associated with an increased survival, while higher POU2F1 expression is associated with a reduced survival (average difference of 25.9 months survival). In summary, in the datasets examined FOS represents an apoptosis-driver and high POU2F1 represents a driver mechanism for cancer development.
Background
Although patients with acute myeloid leukemia (AML) were shown to have an increased risk of thrombosis, no thrombosis risk assessment scoring system has been developed for AML patients. The Khorana Risk Score (KRS), which has been widely used for thrombosis risk assessment in the clinical setting, was developed on the basis of solid tumor data and has not been validated among AML patients. This study aims to validate the use of the KRS as a thrombosis risk-scoring system among patients with AML.
Methods
Using data from H. Lee Moffitt Cancer Center and Research Institution’s Total Cancer Care Research Study, we retrospectively identified patients who were histologically confirmed with AML from 2000 to 2018. Clinical and laboratory variables at the time of AML diagnosis were characterized and analyzed. The thrombotic event rate was estimated with the Kaplan-Meier method and compared using the log-rank test.
Results
A total of 867 AML patients were included in the analysis. The median age at AML diagnosis was 75 years (range, 51–96), and the majority were male (65%,
n
= 565). A total of 22% (
n
= 191), 51% (
n
= 445), 24% (
n
= 207), and 3% (
n
= 24) of patients had a KRS of 0, 1, 2, and 3, respectively. A total of 42 thrombotic events (3% [
n
= 6/191] with a KRS of 1; 5% [
n
= 23/445] with a KRS of 2; 6.3% [
n
= 13/207] with a KRS of 3) were observed, with a median follow-up of 3 months (range, 0.1–307). There was no statistical difference in the risk of thrombosis between these groups (
P
= .1949).
Conclusions
Although there was an increased risk of thrombosis associated with a higher KRS among AML patients with a KRS of 1 to 3, the difference was not statistically significant. Furthermore, only a few patients were found to have a KRS > 3, and this was largely due to pancytopenia, which is commonly associated with AML. These results indicate the need for a better thrombotic risk-scoring system for AML patients.
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