Breast-Lesion Characterization using Textural Features of Quantitative Ultrasound Parametric Maps

© 2017 The Author(s). This study evaluated, for the first time, the efficacy of quantitative ultrasound (QUS) spectral parametric maps in conjunction with texture-analysis techniques to differentiate non-invasively benign versus malignant breast lesions. Ultrasound B-mode images and radiofrequency data were acquired from 78 patients with suspicious breast lesions. QUS spectral-analysis techniques were performed on radiofrequency data to generate parametric maps of mid-band fit, spectral slope, spectral intercept, spacing among scatterers, average scatterer diameter, and average acoustic concentration. Texture-analysis techniques were applied to determine imaging biomarkers consisting of mean, contrast, correlation, energy and homogeneity features of parametric maps. These biomarkers were utilized to classify benign versus malignant lesions with leave-one-patient-out cross-validation. Results were compared to histopathology findings from biopsy specimens and radiology reports on MR images to evaluate the accuracy of technique. Among the biomarkers investigated, one mean-value parameter and 14 textural features demonstrated statistically significant differences (p < 0.05) between the two lesion types. A hybrid biomarker developed using a stepwise feature selection method could classify the legions with a sensitivity of 96%, a specificity of 84%, and an AUC of 0.97. Findings from this study pave the way towards adapting novel QUS-based frameworks for breast cancer screening and rapid diagnosis in clinic

Identification of MSRA gene on chromosome 8p as a candidate metastasis suppressor for human hepatitis B virus-positive hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>The prognosis of patients with hepatocellular carcinoma (HCC) still remains very dismal, which is mainly due to metastasis. In our previous studies, we found that chromosome 8p deletions might contribute to metastasis of HCC. In this study, we aimed to identify the candidate metastatic suppressor gene on chromosome 8p.</p> <p>Methods</p> <p>Oligo-nucleotide microarrays which included 322 genes on human chromosome 8p were constructed to analyze the difference in gene expression profiles between HCC tissues with and without metastasis. The leading differentially expressed genes were identified and selected for further analysis by real-time PCR and Western blotting. Recombinant expression plasmid vectors for each target gene were constructed and transfected into HCC cells and its <it>in vitro </it>effects on proliferation and invasion of HCC cells were also investigated.</p> <p>Results</p> <p>Sixteen leading differentially expressed genes were identified from the HCC tissues with metastasis compared with those without metastasis (<it>p </it>< 0.01, <it>q </it>< 16 %). Among of the 10 significantly down-regulated genes in HCC with metastasis, methionine sulfoxide reductase A (<it>MSRA</it>) had the lowest <it>p </it>value and false discovery rate (FDR), and was considered as a potential candidate for metastasis suppressor gene. Real-time PCR and Western blotting confirmed that the mRNA and protein expression levels of <it>MSRA </it>were significantly decreased in HCC with metastasis compared with those without metastasis (<it>p </it>< 0.001), and <it>MSRA </it>mRNA level in HCCLM6 cells (with high metastatic potential) was also much lower than that of other HCC cell lines. Transfection of a recombinant expression plasmid vector and overexpression of <it>MSRA </it>gene could obviously inhibit cell colony formation (4.33 ± 2.92 vs. 9.17 ± 3.38, <it>p </it>= 0.008) and invasion (7.40 ± 1.67 vs. 17.20 ± 2.59, <it>p</it>= 0.0001) of HCCLM6 cell line.</p> <p>Conclusion</p> <p><it>MSRA </it>gene on chromosome 8p might possess metastasis suppressor activity in HCC.</p

Validation of differential gene expression algorithms: Application comparing fold-change estimation to hypothesis testing

<p>Abstract</p> <p>Background</p> <p>Sustained research on the problem of determining which genes are differentially expressed on the basis of microarray data has yielded a plethora of statistical algorithms, each justified by theory, simulation, or ad hoc validation and yet differing in practical results from equally justified algorithms. Recently, a concordance method that measures agreement among gene lists have been introduced to assess various aspects of differential gene expression detection. This method has the advantage of basing its assessment solely on the results of real data analyses, but as it requires examining gene lists of given sizes, it may be unstable.</p> <p>Results</p> <p>Two methodologies for assessing predictive error are described: a cross-validation method and a posterior predictive method. As a nonparametric method of estimating prediction error from observed expression levels, cross validation provides an empirical approach to assessing algorithms for detecting differential gene expression that is fully justified for large numbers of biological replicates. Because it leverages the knowledge that only a small portion of genes are differentially expressed, the posterior predictive method is expected to provide more reliable estimates of algorithm performance, allaying concerns about limited biological replication. In practice, the posterior predictive method can assess when its approximations are valid and when they are inaccurate. Under conditions in which its approximations are valid, it corroborates the results of cross validation. Both comparison methodologies are applicable to both single-channel and dual-channel microarrays. For the data sets considered, estimating prediction error by cross validation demonstrates that empirical Bayes methods based on hierarchical models tend to outperform algorithms based on selecting genes by their fold changes or by non-hierarchical model-selection criteria. (The latter two approaches have comparable performance.) The posterior predictive assessment corroborates these findings.</p> <p>Conclusions</p> <p>Algorithms for detecting differential gene expression may be compared by estimating each algorithm's error in predicting expression ratios, whether such ratios are defined across microarray channels or between two independent groups.</p> <p>According to two distinct estimators of prediction error, algorithms using hierarchical models outperform the other algorithms of the study. The fact that fold-change shrinkage performed as well as conventional model selection criteria calls for investigating algorithms that combine the strengths of significance testing and fold-change estimation.</p

Overexpression of circulating MiR-30b-5p identifies advanced breast cancer

Breast cancer (BrC) remains the leading cause of cancer-related death in women, mainly due to recurrent and/or metastatic events, entailing the need for biomarkers predictive of progression to advanced disease. MicroRNAs hold promise as noninvasive cancer biomarkers due to their inherent stability and resilience in tissues and bodily fluids. There is increasing evidence that specific microRNAs play a functional role at different steps of the metastatic cascade, behaving as signaling mediators to enable the colonization of a specific organ. Herein, we aimed to evaluate the biomarker performance of microRNAs previously reported as associated with prognosis for predicting BrC progression in liquid biopsies. Background Breast cancer (BrC) remains the leading cause of cancer-related death in women, mainly due to recurrent and/or metastatic events, entailing the need for biomarkers predictive of progression to advanced disease. MicroRNAs hold promise as noninvasive cancer biomarkers due to their inherent stability and resilience in tissues and bodily fluids. There is increasing evidence that specific microRNAs play a functional role at different steps of the metastatic cascade, behaving as signaling mediators to enable the colonization of a specific organ. Herein, we aimed to evaluate the biomarker performance of microRNAs previously reported as associated with prognosis for predicting BrC progression in liquid biopsies. Methods Selected microRNAs were assessed using a quantitative reverse transcription-polymerase chain reaction in a testing cohort of formalin-fixed paraffin-embedded primary (n = 16) and metastatic BrC tissues (n = 22). Then, miR-30b-5p and miR-200b-3p were assessed in a validation cohort #1 of formalin-fixed paraffin-embedded primary (n = 82) and metastatic BrC tissues (n = 93), whereas only miR-30b-5p was validated on a validation cohort #2 of liquid biopsies from BrC patients with localized (n = 20) and advanced (n = 25) disease. ROC curve was constructed to evaluate prognostic performance. Results MiR-30b-5p was differentially expressed in primary tumors and paired metastatic lesions, with bone metastases displaying significantly higher miR-30b-5p expression levels, paralleling the corresponding primary tumors. Interestingly, patients with advanced disease disclosed increased circulating miR-30b-5p expression compared to patients with localized BrC. Conclusions MiR-30b-5p might identify BrC patients at higher risk of disease progression, thus, providing a useful clinical tool for patients’ monitoring, entailing earlier and more effective treatment. Nonetheless, validation in larger multicentric cohorts is mandatory to confirm these findings.Research Center of Portuguese Oncology Institute of Porto (PI 74-CI-IPOP-19-2016). JL and CSG are supported by a PhD fellowship from FCT - Fundação para a Ciência e Tecnologia (SFRH/ BD/132751/2017 and SFRH/BD/92786/2013, respectively). SS is supported by a PhD fellowship IPO/ESTIMA-1 NORTE-01-0145-FEDER-000027. BMC is funded by FCT-Fundação para a Ciência e a Tecnologia (IF/00601/2012

Transforming Growth Factor β Signaling Pathway Associated Gene Polymorphisms May Explain Lower Breast Cancer Risk in Western Indian Women

Transforming growth factor β1 (TGFB1) T29C and TGF β receptor type 1 (TGFBR1) 6A/9A polymorphisms have been implicated in the modulation of risk for breast cancer in Caucasian women. We analyzed these polymorphisms and combinations of their genotypes, in pre menopausal breast cancer patients (N = 182) and healthy women (N = 236) from western India as well as in breast cancer patients and healthy women from the Parsi community (N = 48 & 171, respectively). Western Indian women were characterized by a higher frequency of TGFB1*C allele of the TGF β T29C polymorphism (0.48 vs 0.44) and a significantly lower frequency of TGFBR1*6A allele of the TGFBR1 6A/9A polymorphism (0.02 vs 0.068, p<0.01) as compared to healthy Parsi women. A strong protective effect of TGFB1*29C allele was seen in younger western Indian women (<40 yrs; OR = 0.45, 95% CI 0.25–0.81). Compared to healthy women, the strikingly higher frequencies of low or intermediate TGF β signalers in patients suggested a strong influence of the combination of these genotypes on the risk for breast cancer in Parsi women (for intermediate signalers, OR = 4.47 95%CI 1.01–19.69). The frequency of low signalers in Parsi healthy women, while comparable to that reported in Europeans and Americans, was three times higher than that in healthy women from western India (10.6% vs 3.3%, p<0.01). These observations, in conjunction with the low incidence rate of breast cancer in Indian women compared to White women, raise a possibility that the higher frequency of TGFB1*29C allele and lower frequency of TGFBR1*6A allele may represent important genetic determinants that together contribute to a lower risk of breast cancer in western Indian women

The influence of nativity and neighborhoods on breast cancer stage at diagnosis and survival among California Hispanic women

<p>Abstract</p> <p>Background</p> <p>In the US, foreign-born Hispanics tend to live in socioeconomic conditions typically associated with later stage of breast cancer diagnosis, yet they have lower breast cancer mortality rates than their US-born counterparts. We evaluated the impact of nativity (US- versus foreign-born), neighborhood socioeconomic status (SES) and Hispanic enclave (neighborhoods with high proportions of Hispanics or Hispanic immigrants) on breast cancer stage at diagnosis and survival among Hispanics.</p> <p>Methods</p> <p>We studied 37,695 Hispanic women diagnosed from 1988 to 2005 with invasive breast cancer from the California Cancer Registry. Nativity was based on registry data or, if missing, imputed from case Social Security number. Neighborhood variables were developed from Census data. Stage at diagnosis was analyzed with logistic regression, and survival, based on vital status determined through 2007, was analyzed with Cox proportional hazards regression.</p> <p>Results</p> <p>Compared to US-born Hispanics, foreign-born Hispanics were more likely to be diagnosed at an advanced stage of breast cancer (adjusted odds ratio (OR) = 1.14, 95% confidence interval (CI): 1.09-1.20), but they had a somewhat lower risk of breast cancer specific death (adjusted hazard ratio (HR) = 0.94, 95% CI: 0.90-0.99). Living in low SES and high enclave neighborhoods was associated with advanced stage of diagnosis, while living in a lower SES neighborhood, but not Hispanic enclave, was associated with worse survival.</p> <p>Conclusion</p> <p>Identifying the modifiable factors that facilitate this survival advantage in Hispanic immigrants could help to inform specific interventions to improve survival in this growing population.</p

Propofol-Induced Changes in Neurotrophic Signaling in the Developing Nervous System In Vivo

Several studies have revealed a role for neurotrophins in anesthesia-induced neurotoxicity in the developing brain. In this study we monitored the spatial and temporal expression of neurotrophic signaling molecules in the brain of 14-day-old (PND14) Wistar rats after the application of a single propofol dose (25 mg/kg i.p). The structures of interest were the cortex and thalamus as the primary areas of anesthetic actions. Changes of the protein levels of the brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), their activated receptors tropomyosin-related kinase (TrkA and TrkB) and downstream kinases Akt and the extracellular signal regulated kinase (ERK) were assessed by Western immunoblot analysis at different time points during the first 24 h after the treatment, as well as the expression of cleaved caspase-3 fragment. Fluoro-Jade B staining was used to follow the appearance of degenerating neurons. The obtained results show that the treatment caused marked alterations in levels of the examined neurotrophins, their receptors and downstream effector kinases. However, these changes were not associated with increased neurodegeneration in either the cortex or the thalamus. These results indicate that in the brain of PND14 rats, the interaction between Akt/ERK signaling might be one of important part of endogenous defense mechanisms, which the developing brain utilizes to protect itself from potential anesthesia-induced damage. Elucidation of the underlying molecular mechanisms will improve our understanding of the age-dependent component of anesthesia-induced neurotoxicity

The Characteristics of Blood Glucose and WBC Counts in Peripheral Blood of Cases of Hand Foot and Mouth Disease in China: A Systematic Review

Background: Outbreaks of Hand Foot and Mouth Disease (HFMD) have occurred in many parts of the world especially in China. We aimed to summarize the characteristics of the levels of blood glucose and white blood cell (WBC) counts in cases of HFMD in Mainland China and Taiwan, using meta-analysis based on systematic review of published articles. Methods: We systematically reviewed published studies, from the MEDLINE and WANFANG Data, about the levels of blood glucose and WBC counts in cases of HFMD until 15 th June 2011, and quantitatively summarized the characteristics of them using meta-analysis. Results: In total, 37 studies were included in this review. In Mainland China and Taiwan, generally, the average level of blood glucose, the prevalence of hyperglycemia, WBC counts and the prevalence of leukocytosis increased with the severity of the illness. There was no significant difference in the prevalence of leukocytosis between ANS (autonomic nervous system dysregulation)/PE (pulmonary edema) group and CNS (central nervous system) group, and in the average level of blood glucose between healthy controls and mild cases of HFMD. WBC counts in cases infected by EV71 were less than those in cases infected by CA16. Conclusions: our analyses indicated that blood glucose and WBC counts increased with the severity of HFMD disease, which would help doctors to manage patients efficiently

What is the potential for bisexual men in China to act as a bridge of HIV transmission to the female population? Behavioural evidence from a systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>HIV prevalence among men who have sex with men (MSM) in China has rapidly increased in recent years. It is suggested that MSM could be a potential bridge of HIV transmission to the general female population. We investigated the bisexual behaviour of MSM in China through systematic review and meta-analysis.</p> <p>Methods</p> <p>We conducted a systematic review and meta-analyses on published peer-reviewed Chinese and English literature during 2001-2010 according to the PRISMA guidelines. Marital status and sexual behavioural indicators of MSM were presented graphically using forest plots. The pooled effect rates with 95% confidence intervals were also calculated. Meta-regression analyses were performed to examine the factors associated with high heterogeneities across the studies.</p> <p>Results</p> <p>Forty-three eligible articles (11 in English and 32 in Chinese) were identified. Our results showed that 17.0% (95% CI: 15.1-19.1%) of MSM in China are currently married to a woman and 26.3% (95% CI: 23.6-29.1%) of MSM had female sexual partners in the last six months. The pooled estimates for condom use rate between MSM and female sex partners was 41.4% (95% CI: 35.5-47.5%) at the last sex act; and 25.6% (95% CI: 23.0-28.4%) in the last six months. The consistent condom use rates with regular, non-commercial, casual and commercial female sex partners in the last six months were 23.3% (95% CI: 11.25-42.1%), 39.0% (95% CI: 28.8-50.3%) and 55.8% (95% CI: 41.4-69.4%), respectively.</p> <p>Conclusions</p> <p>A substantial proportion of Chinese MSM is currently married or had sexual relations with a female in the past six months. In addition, low condom usage was common between married MSM and their wives, hence posing a higher risk of transmitting HIV. Harm-reduction programs targeting married MSM and their female partners are necessary to curb the further spread of HIV infection to the general female population.</p