Background
In human breast, adipose tissue represents up to 80% of the total volume and plays a critical role in mammary gland remodeling. Given the emerging role of obesity in breast cancer growth ...and development, we explored the relationship between body mass index (BMI), as a proxy of woman’s obesity status, and the expression in normal breast tissue from healthy women of a selected panel of genes, known to be involved in mammary gland homeostasis.
Methods
Two independent publicly available datasets, composed of 180 specimens of normal breast tissue from reduction mammoplasty were interrogated. Differential gene expression among BMI classes was evaluated by ANOVA, and partial correlation coefficient was used to assay the correlation between genes controlling for BMI.
Results
Despite the differences in microarray platforms and analytical procedures, the two datasets shared a core of 9 genes differentially expressed in BMI classes and significantly correlated with BMI. Four (44%) of these genes belong to the functional class of cytokines and cytokine receptors (
IL1R1
,
IL2RA
,
IL12A
, and
IL12RB2
). The others belong to the functional class of the epigenetic regulation (
MEDAG
and
SETD7
), signal transduction (
STAT1
), cell adhesion (
ITGAV
), and enzymatic activity (
STS
).
Conclusions
Although exploratory, present findings are in agreement with the role of inflammation modulators in the homeostasis of normal breast tissue and the believe that an increase in body adipose tissue may have a potentially dangerous local effect, through the increased expression of inflammation-related genes and the establishment of a low-grade chronic inflammation.
Purpose: To investigate the association between the bird-beak configuration (BBC), a wedge-shaped gap between the undersurface of a thoracic endograft and the lesser curvature of the arch after ...thoracic endovascular aortic repair (TEVAR), and postoperative outcome after TEVAR. Methods: The study was performed according to the PRISMA guidelines. The PubMed, EMBASE, and Cochrane databases were searched to identify all case series reporting BBC after TEVAR between 2006 and April 2018. Data analysis was performed considering the difference in the risk of complications for presence vs absence of BBC. After screening 1633 articles, 21 studies were identified that matched the selection criteria; 12 of these reported detailed information to investigate the postoperative outcome using proportion meta-analysis with a random effects model. The pooled risk difference is reported with the 95% confidence interval (CI). Heterogeneity of the included studies was assessed with the I2 statistic (low 25%, medium 50%, high 75%). Results: Complications occurred within a range of 0 to 72 months in 14.7% (95% CI 7.4% to 27.3%) of patients with BBC and in 6.3% (95% CI 2.5% to 15.4%) of patients without BBC. A cumulative incidence could not be assessed. The summary risk difference was 11.1% (95% CI −0.1% to 22.3%, p=0.052). There was significant heterogeneity (I2=85.6%). The Egger test did not show evidence of publication bias (p=0.975). When specifically considering type Ia endoleak and endograft migration, the risk difference between BBC and non-BBC patients was 8.2% (95% CI 0.3% to 16.1%, p=0.042; I2=69.0%). The specific risk difference for endograft collapse/infolding and thrombosis was 3.7% (95% CI −3.5% to 11.1%, p=0.308; I2=10.2%). Conclusion: At present the literature does not provide statistical evidence to establish an overall prognostic value of the BBC. Nevertheless, the BBC appears to be associated with a high risk of type Ia endoleak and endograft migration, which warrants specific and long-term surveillance. Clinically relevant values for BBC grading should be established to perhaps define indications for preemptive treatment based on the presence of BBC only.
We study event rates over time (event dynamics) in patients undergoing surgery for early-stage non–small-cell lung cancer (NSCLC).
Using a database of patients undergoing initial surgery for NSCLC, ...the event dynamics, based on the hazard rate, were evaluated. Events evaluated included time to any treatment failure, local recurrence, distant metastasis (DM), and development of a second primary lung cancer.
Among 1506 patients, time to any treatment failure dynamics demonstrated an initial surge in the hazard rate 9 months after surgery, followed by two smaller peaks at the end of the second and fourth years, respectively. This pattern was dominated by DM events. Two distinguishable peaks were noted for local recurrence in the first and second years. In contrast, the hazard rate for second primary lung cancer exhibited a more uniform pattern over time. The DM dynamics was analyzed by sex and three peaks emerged for both sexes. The timing of the first peak was similar for both sexes, at 7 to 9 months after surgery. The second peak occurred earlier in men (18–20 months) than women (24–26 months). For both sexes the third peak appeared during the fourth year.
Recurrence dynamics of resected early-stage NSCLC displays a multipeak pattern, which supports the hypothesis of a metastasis growth model previously described for early-stage breast cancer. The model assumes both cellular and micrometastatic tumor dormancy and a transient phase of acceleration of metastatic growth following surgical excision of the primary tumor.
Background
Localized to cell membrane, γ-glutamyl transferase (GGT) is a reliable marker for the evaluation of cell distress occurring in several pathological conditions including obesity, metabolic ...syndrome, and cancer. In particular, high GGT serum levels are associated with breast cancer incidence and progression.
Methods
The tissue expression of
GGT1,
the gene coding for GGT, was investigated in silico in a large case series of paired samples of breast cancer and adjacent histologically normal (HN) tissue, and in a collection of healthy breast tissues from reduction mammoplasty. The association of
GGT1
with patient’s body mass index (BMI), and the relationship between
GGT1
and a panel of genes involved in apoptosis, IGF-1 signaling, or coding for adipokines and adipokine receptors were also investigated.
Results
GGT1
expression was significantly higher in tumor than in the adjacent HN tissue (
P
= 0.0002). Unexpectedly, the expression of
GGT1
was inversely associated with BMI in normal and HN tissue, whereas no correlation was found in cancerous tissue. In all tissues,
GGT1
correlated positively with
TP53
and negatively with
BCL2
and
LEPR,
whereas only in normal and HN tissue
GGT1
correlated positively with
IGF1R
. The linear regression model, adjusted for BMI, showed no confounding effect on any correlation, except for the correlation of
GGT1
with
LEPR
in normal tissue from healthy women.
Conclusions
Even if present results provide interesting insights on the still elusive mechanism(s) underlying the association between obesity and epithelial cell proliferation, possibly promoting neoplastic transformation, such relationship deserves further investigation in other independent datasets.
Purpose
Scarce information on the prevalence and characteristics of olfactory disfunction (OD) in type 2 diabetic (T2D) patients are available. The aims of this study were (1) to assess the olfactory ...function in T2D patients and to compare it with a control group of individuals without T2D, and (2) to evaluate the differences in OD within T2D patients according to the presence of diabetic complications.
Methods
A group of 39 T2D patients and a control group of 39 healthy individuals were enrolled. Each subject underwent an evaluation of the olfactory performance using the Sniffing Olfactory Screening Test (SOST) and completed a questionnaire assessing the subjective perception of olfaction. According to the presence of diabetic complications, the group of T2D patients was divided into two subgroups. Non-parametric tests and regression analysis were used for statistical analysis.
Results
No differences in the subjective perception of olfaction were demonstrated among T2D patients (with and without complications) and controls. A significant difference for the SOST score was demonstrated among the different groups. In particular, OD was more frequent in T2D patients than in controls. In addition, OD was far more frequent in T2D patients with complications. Regression analysis did not demonstrate any significant association between OD and clinical/demographic characteristics of T2D patients.
Conclusion
T2D patients were more frequently affected by OD. The subgroup analysis suggested a possible relationship between OD and diabetic complications since patients with T2D diabetic complications demonstrated lower olfactory abilities than controls subjects and T2D patients without diabetic complications.
In exploring the time course of a disease to support or generate biological hypotheses, the shape of the hazard function provides relevant information. For long follow-ups the shape of hazard ...function may be complex, with the presence of multiple peaks. In this paper we present the use of a neural network extension of the piecewise exponential model to study the shape of the hazard function in time in dependence of covariates. The technique is applied to a dataset of 247 renal cell carcinoma patients from a randomized clinical trial.
An interaction effect of treatment with number of metastatic lymph nodes but not with pathologic T-stage is highlighted.
Piecewise Exponential Artificial Neural Networks demonstrate a clinically useful and flexible tool in assessing interaction or time-dependent effects of the prognostic factors on the hazard function.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract The pandemic of coronavirus disease 19 (COVID-19), caused by severe respiratory syndrome coronavirus 2 (SARS-CoV-2), had severe repercussions for breast cancer patients. Increasing evidence ...indicates that SARS-CoV-2 infection may directly impact breast cancer biology, but the effects of SARS-CoV-2 on breast tumor cells are still unknown. Here, we analyzed the molecular events occurring in the MCF7, MDA-MB-231 and HCC1937 breast cancer cell lines, representative of the luminal A, basal B/claudin-low and basal A subtypes, respectively, upon SARS-CoV-2 infection. Viral replication was monitored over time, and gene expression profiling was conducted. We found that MCF7 cells were the most permissive to viral replication. Treatment of MCF7 cells with Tamoxifen reduced the SARS-CoV-2 replication rate, suggesting an involvement of the estrogen receptor in sustaining virus replication in malignant cells. Interestingly, a metagene signature based on genes upregulated by SARS-CoV-2 infection in all three cell lines distinguished a subgroup of premenopausal luminal A breast cancer patients with a poor prognosis. As SARS-CoV-2 still spreads among the population, it is essential to understand the impact of SARS-CoV-2 infection on breast cancer, particularly in premenopausal patients diagnosed with the luminal A subtype, and to assess the long-term impact of COVID-19 on breast cancer outcomes.
In high-dimensional data (HDD) settings, the number of variables associated with each observation is very large. Prominent examples of HDD in biomedical research include omics data with a large ...number of variables such as many measurements across the genome, proteome, or metabolome, as well as electronic health records data that have large numbers of variables recorded for each patient. The statistical analysis of such data requires knowledge and experience, sometimes of complex methods adapted to the respective research questions.
Advances in statistical methodology and machine learning methods offer new opportunities for innovative analyses of HDD, but at the same time require a deeper understanding of some fundamental statistical concepts. Topic group TG9 "High-dimensional data" of the STRATOS (STRengthening Analytical Thinking for Observational Studies) initiative provides guidance for the analysis of observational studies, addressing particular statistical challenges and opportunities for the analysis of studies involving HDD. In this overview, we discuss key aspects of HDD analysis to provide a gentle introduction for non-statisticians and for classically trained statisticians with little experience specific to HDD.
The paper is organized with respect to subtopics that are most relevant for the analysis of HDD, in particular initial data analysis, exploratory data analysis, multiple testing, and prediction. For each subtopic, main analytical goals in HDD settings are outlined. For each of these goals, basic explanations for some commonly used analysis methods are provided. Situations are identified where traditional statistical methods cannot, or should not, be used in the HDD setting, or where adequate analytic tools are still lacking. Many key references are provided.
This review aims to provide a solid statistical foundation for researchers, including statisticians and non-statisticians, who are new to research with HDD or simply want to better evaluate and understand the results of HDD analyses.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
During follow-up patients may experience non-fatal events related to disease progression and death. This is a “semi-competing risks” setting, as the occurrence of death before non-fatal events ...prevents the observation of the latter, but not vice versa. We developed a regression model for non-fatal event free survival in the presence of semi-competing risks based on pseudo-values. It is estimated in three steps: estimate non-parametrically non-fatal event free survival under a defined copula representing the joint distribution of time to fatal and non-fatal events; compute non-fatal event free survival pseudo-values for every individual at predefined time points; fit a GEE model using pseudo-values as a response variable. A simulation study is performed and two clinical examples are analysed. The proposed method provides covariate coefficient estimates almost unbiased, with standard errors slightly higher than those obtained with methods based on maximum likelihood estimation. However, pseudo-values regression, being based on estimation functions, has the advantage of enabling adjusted covariate effects estimation without convergence problems and allowing a direct smoothed estimate of the hazard function. Moreover, standard routines computing pseudo-values and GEE are available in statistical software.
Lung clearance index (LCI) is accepted as an early marker of lung disease in cystic fibrosis (CF), however the utility of LCI to identify subgroups of CF disease in the paediatric age group has never ...been explored. The aim of the study was to characterize phenotypes of children with CF using LCI as a marker of ventilation inhomogeneity and to investigate whether these phenotypes distinguished patients based on time to pulmonary exacerbation (PE).
Data were collected on patients with CF aged < 18 years old, attending the CF Center of Milan during outpatient follow-up visits between October 2014 and September 2019. Cluster analysis using agglomerative nesting hierarchical method was performed to generate distinct phenotypes. Time-to-recurrent event analysis investigated association of phenotypes with PE.
We collected 313 multiple breath washout tests on 125 children aged 5.5-16.8 years. Cluster analysis identified two divergent phenotypes in children and adolescents of same age, presenting with almost normal FEV
but with substantial difference in markers of ventilation inhomogeneity (mean LCI difference of 3.4, 95% Confidence Interval CI 2.6-4.2). A less severe phenotype was associated with a lower risk of PE relapse (Hazard Ratio 0.45, 95% CI 0.34-0.62).
LCI is useful in clinical practice to characterize distinct phenotypes of children and adolescents with mild/normal FEV
. A less severe phenotype translates into a lower risk of PE relapse.
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