A Long Noncoding RNA Signature That Predicts Pathological Complete Remission Rate Sensitively in Neoadjuvant Treatment of Breast Cancer

BACKGROUND: Mounting evidence suggests that long noncoding RNAs (lncRNAs) are closely related to pathological complete response (pCR) in neoadjuvant treatment of breast cancer. Here, we construct lncRNA associated models to predict pCR rate. METHODS: LncRNA expression profiles of breast cancer patients treated with neoadjuvant chemotherapy (NAC) were obtained from Gene Expression Omnibus by repurposing existing microarray data. The prediction model was firstly built by analyzing the correlation between pCR and lncRNA expression in the discovery dataset GSE 25066 (n = 488). Another three independent datasets, GSE20194 (n = 278), GSE20271 (n = 178), and GSE22093 (n = 97), were integrated as the validation cohort to assess the prediction efficiency. RESULTS: A novel lncRNA signature (LRS) consisting of 36 lncRNAs was identified. Based on this LRS, patients with NAC treatment were divided into two groups: LRS-high group and LRS-low group, with positive correlation of pCR rate in the discovery dataset. In the validation cohort, univariate and multivariate analyses both demonstrated that high LRS was associated with higher pCR rate. Subgroup analysis confirmed that this model performed well in luminal B [odds ratio (OR) = 5.4; 95% confidence interval (CI) = 2.7-10.8; P = 1.47e-06], HER2-enriched (OR = 2.5; 95% CI = 1.1-5.7; P = .029), and basal-like (OR = 5.5; 95% CI = 2.3-16.2; P = 5.32e-04) subtypes. Compared with other preexisting prediction models, LRS demonstrated better performance with higher area under the curve. Functional annotation analysis suggested that lncRNAs in this signature were mainly involved in cancer proliferation process. CONCLUSION: Our findings indicated that our lncRNA signature was sensitive to predict pCR rate in the neoadjuvant treatment of breast cancer, which deserves further evaluation.     

NFATc1 Expression as a Prognosticator in Urothelial Carcinoma of the Upper Urinary Tract

We recently found that NFATc1, a member of the NFAT family and a key regulator of the immune response, could induce bladder carcinogenesis and cancer progression. In this study, we immunohistochemically stained for NFATc1 in upper urinary tract urothelial carcinoma (UUTUC) specimens and paired nonneoplastic urothelial tissues. NFATc1 was positive in 51 [52%; 40 (40%) weak (1+), 9 (9%) moderate (2+), and 2 (2%) strong (3+)] of 99 UUTUCs, which was significantly higher than in benign urothelium [30 (36%) of 83; 28 (34%) weak and 2 (2%) moderate] (0 vs 1+/2+/3+, P = .038; 0/1+ vs 2+/3+, P = .023). There were no significant associations between NFATc1 expression pattern and tumor grade or pT stage. However, the positive rates of NFATc1 expression tended to be higher in renal pelvic tumors (60%) than in ureteral tumors (42%; P = .080) as well as in pN+ tumors (75%) than in pN0 tumors (49%; P = .089). Kaplan-Meier and log-rank tests revealed that moderate (2+) to strong (3+) NFATc1 expression correlated with lower progression-free survival (P = .032) and cancer-specific survival (P = .005) rates in the 99 cases. Patients with high (2+/3+) NFATc1 muscle-invasive tumor (n = 9) also had a significantly higher risk of cancer-specific mortality (P = .021) compared to those with low (0/1+) NFATc1 muscle-invasive tumor (n = 53). Thus, compared with nonneoplastic urothelium, a significant increase in the expression of NFATc1 in UUTUC was seen, implying the involvement of NFATc1 signals in the development of UUTUC. The current results further suggest that NFATc1 overexpression serves as a predictor of poor prognosis in patients with UUTUC.     

Identification of reference microRNAs and suitability of archived hemopoietic samples for robust microRNA expression profiling

In many cancers, including neuroblastoma, microRNA (miRNA) expression profiling of peripheral blood (PB) and bone marrow (BM) may increase understanding of the metastatic process and lead to the identification of clinically informative biomarkers. The quality of miRNAs in PB and BM samples archived in PAXgene? blood RNA tubes from large-scale clinical studies and the identity of reference miRNAs for standard reporting of data are to date unknown. In this study, we evaluated the reliability of expression profiling of 377 miRNAs using quantitative polymerase chain reaction (qPCR) in PB and BM samples (n = 90) stored at ?80 °C for up to 5 years in PAXgene? blood RNA tubes. There was no correlation with storage time and variation of expression for any single miRNA (r < 0.50). The profile of miRNAs isolated as small RNAs or co-isolated with small/large RNAs was highly correlated (r = 0.96). The mean expression of all miRNAs and the geNorm program identified miR-26a, miR-28-5p, and miR-24 as the most stable reference miRNAs. This study describes detailed methodologies for reliable miRNA isolation and profiling of PB and BM, including reference miRNAs for qPCR normalization, and demonstrates the suitability of clinical samples archived at ?80 °C into PAXgene? blood RNA tubes for miRNA expression studies.     

Utility of Genomic Analysis in Differentiating Synchronous and Metachronous Lung Adenocarcinomas from Primary Adenocarcinomas with Intrapulmonary Metastasis

Distinguishing synchronous and metachronous primary lung adenocarcinomas from adenocarcinomas with intrapulmonary metastasis is essential for optimal patient management. In this study, multiple lung adenocarcinomas occurring in the same patient were evaluated using comprehensive histopathologic evaluation supplemented with molecular analysis. The cohort included 18 patients with a total of 52 lung adenocarcinomas. Eleven patients had a new diagnosis of multiple adenocarcinomas in the same lobe (n = 5) or different lobe (n = 6). Seven patients had a history of lung cancer and developed multiple new tumors. The final diagnosis was made in resection specimens (n = 49), fine needle aspiration (n = 2), and biopsy (n = 1). Adenocarcinomas were non‐mucinous, and histopathologic comparison of tumors was performed. All tumors save for one were subjected to ALK gene rearrangement testing and targeted Next Generation Sequencing (NGS). Using clinical, radiologic, and morphologic features, a confident conclusion favoring synchronous/metachronous or metastatic disease was made in 65% of patients. Cases that proved challenging included ones with more than three tumors showing overlapping growth patterns and lacking a predominant lepidic component. Genomic signatures unique to each tumor were helpful in determining the relationship of multiple carcinomas in 72% of patients. Collectively, morphologic and genomic data proved to be of greater value and achieved a conclusive diagnosis in 94% of patients. Assessment of the genomic profiles of multiple lung adenocarcinomas complements the histological findings, enabling a more comprehensive assessment of synchronous, metachronous, and metastatic lesions in most patients, thereby improving staging accuracy. Targeted NGS can identify genetic alterations with therapeutic implications.     

Serum MicroRNAs Related with Chemoradiotherapy Resistance in Advanced-Stage Cervical Squamous Cell Carcinoma

OBJECTIVE: To investigate the serum microRNAs as biomarkers in predicting chemoradiotherapy resistance in advanced-stage cervical squamous cell carcinoma (ACSCC) patients. METHODS: Serum samples were collected from International Federation of Gynecology and Obstetrics (FIGO) stage IIB to IIIB cervical squamous cell carcinoma patients treated with platinum based Concomitant Chemoradiotherapy (CCRT) in our hospital during September 2013 to November 2015. Twenty well-matched samples (10 resistant and 10 sensitive) were chosen to screen the miRNA expression profile using serum samples pooled with microarrays. miRNAs expressed significantly different between two groups were further verified in 131 patients (29 resistant and 102 sensitive) serum samples with TaqMan Real-time PCR. The AUC was used to evaluate the accuracy of the biomarkers for prediction. RESULTS: MiR-136-5, miR-152-3p and miR-206 were expressed significantly different between sensitive and resistant groups. Results of 131 patients verification showed that the levels of miR-206 in sensitive samples and resistant samples were 2.715 ± 0.2115 and 14.64 ± 1.184, respectively, which was significantly different (P < .0001), while miR-136-5p and miR-152-3p could not be tested without pre-amplification reactions. Univariate analysis revealed that miR-206 expression was significantly associated with patients' DFS. Multivariate analysis demonstrated that miR-206 expression, tumor differentiation and pelvic lymph nodes metastasis were the independent prognostic factors associated with DFS in this cohort (P = .008, 0.000, 0.000, respectively). The probability of the prognostic accuracy of miR-206 expression in predicting chemoradiotherapy sensitivity of ACSCC patients was 91.3% (79.3% sensitivity and 92.2% specificity). CONCLUSION: Serum miR-206 is a powerful tool in predicting chemoradiotherapy sensitivity in ACSCC patients.     

Contrast Enhancement on Cone-Beam Breast-CT for Discrimination of Breast Cancer Immunohistochemical Subtypes

PURPOSE: To evaluate whether contrast enhancement on cone-beam breast-CT (CBBCT) could aid in discrimination of breast cancer subtypes and receptor status. METHODS: This study included female patients age >40 years with malignant breast lesions identified on contrast-enhanced CBBCT. Contrast enhancement of malignant breast lesions was standardized to breast fat tissue contrast enhancement. All breast lesions were approved via image-guided biopsy or surgery. Immunohistochemical staining was conducted for expression of estrogen (ER), progesterone (PR), human epidermal growth factor receptor-2 (HER2) and Ki-67 index. Contrast enhancement of breast lesions was correlated with immunohistochemical breast cancer subtypes (Luminal A, Luminal B, HER2 positive, triple negative), receptor status and Ki-67 expression. RESULTS: Highest contrast enhancement was seen for Luminal A lesions (93.6 HU) compared to Luminal B lesions (47.6 HU, P = .002), HER2 positive lesions (83.5 HU, P = .359) and triple negative lesions (45.3 HU, P = .005). Contrast enhancement of HER2 positive lesions was higher than Luminal B lesions (P = .044) and triple negative lesions (P = .039). No significant difference was evident between Luminal B and triple negative lesions (P = .439). Lesions with high Ki-67 index showed lower contrast enhancement than those with low Ki-67 index (P = .0043). ER, PR and HER2 positive lesions demonstrated higher contrast enhancement than their receptor negative counterparts, although differences did not reach statistical significance (P = .1714; P = .3603; P = .2166). CONCLUSIONS: Contrast enhancement of malignant breast lesions on CBBCT correlates with immunohistochemical subtype and proliferative potential. Thereby, CBBCT might aid in selecting individualized treatment strategies for breast cancer patients based on pre-operative imaging.     

Systematic Analysis of the Expression of the Mitochondrial ATP Synthase (Complex V) Subunits in Clear Cell Renal Cell Carcinoma

Mitochondrial dysfunction is common in cancer and the mitochondrial electron transport chain is often affected in carcinogenesis. To date, little is known about the expression of the ATP synthase subunits in clear cell renal cell carcinoma (ccRCC). The NextBio database was used to determine an expression profile of the ATP synthase subunits based on published microarray studies. We observed down-regulation of 23 out of 29 subunits of the ATP synthase. Differential expression was validated exemplarily for 12 genes (ATP5A1, ATP5B, ATPAF1, ATP5C1, ATP5D, ATP5O, ATP5F1, ATP5G1, ATP5G2, ATP5G3, ATP5I, ATP5S; screening cohort ccRCC n = 18 and normal renal tissue n = 10) using real-time PCR. Additional eight genes (ATP5A1, ATP5B, ATPAF1, ATP5F1, ATP5G1, ATP5G2, ATP5G3, ATP5S) were internally validated within an enlarged cohort (ccRCC n = 74; normal renal tissue n = 36). Furthermore, down-regulation of ATP5A1, ATPAF1, ATP5G1/G2/G3 was confirmed on the protein level using Western Blot and immunohistochemistry. We observed that altered expression of ATPAF1 and ATP5G1/G2/G3 was correlated with overall survival in patients with ccRCC. In conclusion, down-regulation of many ATP Synthase subunits occurs in ccRCC and is the basis for the reduced activity of the mitochondrial electron chain. Alteration of the expression of ATP5A1, ATPAF1, and ATP5G1/G2/G3 is characteristic for ccRCC and may be prognostic for ccRCC patients' outcome.     

Sex-specific reliability and multidimensional stability of responses to tests assessing neuromuscular function

The objective of this study was to estimate sex-specific effects in the test–retest cross-reliability of peripheral and central changes in nonlinear and linear measures of a surface electromyography signal during a brief (5 second) and sustained (2 minute) isometric maximal voluntary contraction, combined with superimposed electrical stimulation involving the ankle plantar flexors over five identical trials. In this study, we repeated the testing protocol used in our previous study of 10 women (age 20.9, SD = 0.3 years) (Bernecke et al., 2015) in a group of 10 men (age 21.2, SD = 0.4 years). Despite the central (sex effect; p < 0.05, η_p² > 0.71, SP > 70%) and peripheral fatigability (sex effect; p < 0.01, η_p² > 0.8, SP > 90%) during sustained isometric maximal voluntary contraction, and lower reliability for central activation ratio during brief (intraclass correlation coefficient [ICC] = 0.95 for men and ICC = 0.82 for women) and sustained maximal voluntary contraction (ICC > 0.82 for men and ICC > 0.66 for women) over ankle plantar flexors expressed in women more than in men, all the ICCs of all indices measured by tests assessing neuromuscular function across the five identical test–retest trials were found as meaningful (correlation significance of p < 0.05 was reached) and no significant differences were found between trials for any of the measured variables. In conclusion, the present study demonstrated greater central and peripheral fatigue for female participants following sustained (2 minute) isometric maximal voluntary contraction of the plantar flexor muscles for all repeated trials and indicated an acceptable agreement between measurements of the characteristic variables made using the three different devices (dynamometry, electrical stimulation, and surface electromyography) over time for both sexes.     

Anthropometric dimensions provide reliable estimates of abdominal adiposity: A validation study

Abdominal fat accumulation is a major risk factor for cardiometabolic morbidity and mortality. The purpose of the study is to assess the possibility of developing accurate estimation equations based on body measurements to determine total abdominal (TFA), subcutaneous (SFA) and visceral fat area (VFA). Hungarian volunteers (n = 198) aged between 20 and 81 years were enrolled in the study, which was conducted between July and November 2014. All persons underwent anthropometric measurements and computer tomographic (CT) scanning. Sex-specific multiple linear regression analyses were conducted in a subgroup of 98 participants to generate estimation models, then Bland–Altman's analyses were applied in the cross-validation group to compare their predictive efficiency. The variables best predicting VFA were hip circumference, calf circumference and waist-to-hip ratio (WHR) for males (R² = 0.713; SEE = 5602.1 mm²) and sagittal abdominal diameter (SAD), WHR, thigh circumference and triceps skinfold for females (R² = 0.845; SEE = 3835.6 mm²). The SFA prediction equation included SAD, thigh circumference and abdominal skinfold for males (R² = 0.848; SEE = 4124.1 mm²), body mass index and thigh circumference for females (R² = 0.861; SEE = 5049.7 mm²). Prediction accuracy was the highest in the case of TFA: hip circumference and WHR for males (R² = 0.910; SEE = 5637.2 mm²), SAD, thigh circumference and abdominal skinfold for females (R² = 0.915; SEE = 6197.5 mm²) were used in the equations. The results suggested that deviations in the predictions were independent of the amount of adipose tissue. Estimation of abdominal fat depots based on anthropometric traits could provide a cheap, reliable method in epidemiologic research and public health screening to evaluate the risk of cardiometabolic events.     

MRI Texture Analysis Reflects Histopathology Parameters in Thyroid Cancer – A First Preliminary Study

OBJECT: Thyroid cancer represents the most frequent malignancy of the endocrine system with an increasing incidence worldwide. Novel imaging techniques are able to further characterize tumors and even predict histopathology features. Texture analysis is an emergent imaging technique to extract extensive data from an radiology images. The present study was therefore conducted to identify possible associations between texture analysis and histopathology parameters in thyroid cancer. METHODS: The radiological database was retrospectively reviewed for thyroid carcinoma. Overall, 13 patients (3 females, 23.1%) with a mean age of 61.6 years were identified. The MaZda program was used for texture analysis. The T1-precontrast and T2-weighted images were analyzed and overall 279 texture feature for each sequence was investigated. For every patient cell count, Ki67-index and p53 count were investigated. RESULTS: Several significant correlations between texture features and histopathology were identified. Regarding T1-weighted images, S(0;1)Sum Averg correlated the most with cell count (r = 0.82). An inverse correlations with S(5;0)AngScMom, S(5;0)DifVarnc S(5;0), DiffEntrp and GrNonZeros (r = ?0.69, ?0.66, ?0.69 and ?0.63, respectively) was also identified. For T2-weighted images, Variance with r = 0.63 was the highest coefficient, WavEnLL_S3 correlated inversely with cell count (r = ?0.57). WavEnLL_S2 derived from T1-weighted images was the highest coefficient r = ?0.80, S(0;5)SumVarnc was positively with r = 0.74. Regarding T2-weighted images WavEnHL_s-1 was inverse correlated with Ki67 index (r = ?0.77). S(1;0)Correlat was with r = 0.75 the best correlation with Ki67 index. For T1-weighed images S(5;0)SumofSqs was the best with r = 0.65 with p53 count. For T2-weighted images S(1;?1)SumEntrp was the inverse correlation with r = ?0.72, whereas S(0;4)AngScMom correlated positively with r = 0.63. CONCLUSIONS: MRI texture analysis derived from conventional sequences reflects histopathology features in thyroid cancer. This technique might be a novel noninvasive modality to further characterize thyroid cancer in clinical oncology.     

Common variants of ROCKs and the risk of hypertension,and stroke: Two case-control studies and a follow-up study in Chinese Han population

The Rho kinases (ROCKs) are recognized as a critical regulator of vascular functions in cardiovascular disorders. It is crucial to illustrate the association of ROCKs genetic variation and hypertension and/or stroke events. Herein we aimed at investigating the association of ROCK1 and ROCK2 with hypertension and stroke in Chinese Han population. Seven tagSNPs at ROCK1 and ROCK2 were genotyped in a community-based case-control study consisting of 2012 hypertension cases and 2210 normotensive controls and 4128 subjects were further followed up. In stroke case-control study, 1471 ischemic stroke (IS) inpatients and 607 hemorrhagic stroke (HS) inpatients were collected, and 2443 age-matched controls were selected from the follow-up population. Risks were estimated as odds ratio (OR) and hazard ratio (HR) by logistic and Cox regression. The community-based case-control study didn't identify any significant tagSNPs associated with hypertension even after adjustment for covariates. The follow-up analysis showed that rs1481280 of ROCK1 significantly associated with incident hypertension (HR = 1.130, P = 0.048) after adjusting for covariates. rs7589629 and rs978906 of ROCK2 were significantly associated with incident IS (HR = 1.373, P = 0.004; HR = 1.284, P = 0.026) respectively. In stroke case-control study, rs288980, rs1481280 and rs7237677 were significantly associated with IS and the adjusted ORs (P values) of additive model were 0.879 (0.010), 0.895 (0.036) and 0.857 (0.002) respectively. Furthermore, rs288980, rs7237677 and rs978906 were significantly associated with HS and the adjusted ORs (P values) of additive model were 0.857 (0.025), 0.848 (0.018) and 0.856 (0.027) respectively. Our findings suggest that ROCK1 and ROCK2 contribute to the genetic susceptibility of hypertension and stroke.     

Neptuniibacter pectenicola sp. nov. and Neptuniibacter marinus sp. nov., two novel species isolated from a Great scallop (Pecten maximus) hatchery in Norway and emended description of the genus Neptuniibacter.

Nine isolates obtained from a great scallop hatchery in Norway were characterized using a polyphasic approach. Strains were Gram-negative, aerobic and motile rods with oxidative metabolism. Phylogenetic analysis based on the sequences of 16S rRNA and rpoB genes showed that these strains formed two different groups associated with members of the genus Neptuniibacter. DNA–DNA hybridization (DDH) and Average Nucleotide Identity (ANI) demonstrated that the isolates constituted two novel species of this genus, which can be phenotypically differentiated from their closest relatives. The names Neptuniibacter marinus sp. nov. and Neptuniibacter pectenicola sp. nov are proposed, with ATR 1.1^T (=CECT 8938^T = DSM 100783^T) and LFT 1.8^T (=CECT 8936^T = DSM 100781^T) as respective type strains.     

Antioxidant,anticancer, apoptosis properties and chemical composition of black truffle Terfezia claveryi

Desert truffles are seasonal and important edible fungi that grow wild in many countries around the world. Truffles are natural food sources that have significant compositions. In this work, the antioxidant, chemical composition, anticancer, and antiangiogenesis properties of the Terfezia claveryi truffle were investigated. Solvent extractions of the T. claveryi were evaluated for antioxidant activities using (DPPH, FRAP and ABTS methods). The extracts cytotoxicity on the cancer cell lines (HT29, MCF-7, PC3 and U-87 MG) was determined by MTT assay, while the anti-angiogenic efficacy was tested using ex-vivo assay. All extracts showed moderate anticancer activities against all cancer cells (p < 0.05). The hexane extract inhibited the brain cell line (U-87 MG) with an IC₅₀ of 50 μg/ml and significantly promoted cell apoptosis through the mitochondrial pathway and DNA fragmentation p < 0.001. The ethanol extract demonstrated potent antioxidants; DPPH, FRAP, and ABTS with an IC₅₀ value of 52, 48.5 and 64.7 μg/ml, respectively. In addition, the hexane and ethyl acetate extract significantly (p < 0.001) inhibited the sprouting of microvessels by 100% and 81.2%, at 100 μg/ml, respectively. The GC analysis of the most active extract (hexane) showed the presence of several potent phytochemicals such as stigmasterol, beta-Sitosterol, squalene, lupeol, octadecadienoic acid, and oleic acid.     

Genetic Variations of GWAS-Identified Genes and Neuroblastoma Susceptibility: a Replication Study in Southern Chinese Children

Neuroblastoma is one of the most commonly diagnosed solid cancers for children, and genetic factors may play a critical role in neuroblastoma development. Previous genome-wide association studies (GWASs) have identified nine genes associated with neuroblastoma susceptibility in Caucasians. To determine whether genetic variations in these genes are also associated with neuroblastoma susceptibility in Southern Chinese children, we genotyped 25 polymorphisms within these genes by the TaqMan method in 256 cases and 531 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the strength of the associations. We performed a meta-analysis to further evaluate the associations. Furthermore, we calculated the area under the receiver-operating characteristic curves (AUC) to assess which gene/genes may better predict neuroblastoma risk. We confirmed that CASC15 rs6939340 A > G, rs4712653 T > C, rs9295536 C > A, LIN28B rs221634 A > T, and LMO1 rs110419 A > G were associated with significantly altered neuroblastoma susceptibility. We also confirmed that rs6939340 A > G (G versus A: OR = 1.30, 95% CI = 1.13-1.50) and rs110419 G > A (A versus G: OR = 1.37, 95% CI = 1.19-1.58) were associated with increased neuroblastoma risk for all subjects. We also found that the combination of polymorphisms in CASC15, LIN28B, and LMO1 may be used to predict neuroblastoma risk (AUC = 0.63, 95% CI = 0.59-0.67). Overall, we verified five GWAS-identified polymorphisms that were associated with neuroblastoma susceptibility alteration for Southern Chinese population; however, these results need further validation in studies with larger sample sizes.     

2D and 3D CT Radiomics Features Prognostic Performance Comparison in Non-Small Cell Lung Cancer

OBJECTIVE: To compare 2D and 3D radiomics features prognostic performance differences in CT images of non-small cell lung cancer (NSCLC). METHOD: We enrolled 588 NSCLC patients from three independent cohorts. Two sets of 463 patients from two different institutes were used as the training cohort. The remaining cohort with 125 patients was set as the validation cohort. A total of 1014 radiomics features (507 2D features and 507 3D features correspondingly) were assessed. Based on the dichotomized survival data, 2D and 3D radiomics indicators were calculated for each patient by trained classifiers. We used the area under the receiver operating characteristic curve (AUC) to assess the prediction performance of trained classifiers (the support vector machine and logistic regression). Kaplan–Meier and Cox hazard survival analyses were also employed. Harrell's concordance index (C-Index) and Akaike's information criteria (AIC) were applied to assess the trained models. RESULTS: Radiomics indicators were built and compared by AUCs. In the training cohort, 2D_AUC = 0.653, 3D_AUC = 0.671. In the validation cohort, 2D_AUC = 0.755, 3D_AUC = 0.663. Both 2D and 3D trained indicators achieved significant results (P < .05) in the Kaplan-Meier analysis and Cox regression. In the validation cohort, 2D Cox model had a C-Index = 0.683 and AIC = 789.047; 3D Cox model obtained a C-Index = 0.632 and AIC = 799.409. CONCLUSION: Both 2D and 3D CT radiomics features have a certain prognostic ability in NSCLC, but 2D features showed better performance in our tests. Considering the cost of the radiomics features calculation, 2D features are more recommended for use in the current study.     

Prognostic Value of Molecular Breast Cancer Subtypes based on Her2, ESR1, PGR and Ki67 mRNA-Expression in Muscle Invasive Bladder Cancer

INTRODUCTION: Gene expression analyses have identified similarities between bladder and breast cancer, where clinical risk stratification is based on Her2, ESR1, PGR and Ki67 expression. The aim of the study was to assess the respective marker gene expression in patients treated with radical cystectomy for muscle-invasive bladder cancer (MIBC) and to evaluate the applicability of breast cancer subtypes for MIBC risk stratification. MATERIALS & METHODS: 102 patients treated with radical cystectomy for MIBC were assessed. Using routine FFPE tissue and an IVD validated kit, mRNA expression was measured by single step RT-qPCR. Partition test were employed to define cut-off values for high or low marker gene expression. Association of expression with outcome was assessed using Kaplan-Meier analysis and multivariate cox regression analysis. Finally, we performed validation of our results in the MD-Anderson cohort (n = 57). RESULTS: Cancer specific survival (CSS) was impaired in patients with high gene expression of Her2 (P = 0.0009) and ESR1 (P = 0.04). In the multivariate regression model Her2 expression remained significant for the prediction of CSS (HR = 2.11, CI 1.11-4.21, P = 0.024). Furthermore, molecular stratification by breast cancer subgroups was significant (P = 0.023) for CSS prediction. Especially the differentiation between Her2-positive and Luminal A (HR = 4.41, CI 1.53-18.71, P = 0.004) and Luminal B (HR = 1.96, CI 0.99-4.08, P = 0.053) respectively was an independent prognostic parameter for CSS. External validation resulted in comparable risk stratification with differences in fractional subgroups distribution. CONCLUSION: Gene expression of Her2, ESR1, PGR, Ki67 and corresponding breast cancer subtypes allow a risk-stratification in MIBC, whereby Her2 overexpressing tumors reveal a particularly poor prognosis.     

Bifidobacterium primatium sp. nov., Bifidobacterium scaligerum sp. nov., Bifidobacterium felsineum sp. nov. and Bifidobacterium simiarum sp. nov.: Four novel taxa isolated from the faeces of the cotton top tamarin (Saguinus oedipus) and the emperor tamarin (Saguinus imperator)

Four novel Gram-stain-positive, non spore forming and fructose-6-phosphate phosphoketolase-positive strains were isolated from the faeces of a cotton top tamarin (Saguinus oedipus) and an emperor tamarin (Saguinus imperator). Phylogenetic analyses based on 16S rRNA revealed that bifidobacterial strains TRE 1^T exhibit close phylogenetic relatedness to Bifidobacterium catulorum DSM 103154 (96.0%) and Bifidobacterium tissieri DSM 100201 (96.0%); TRE D^T and TRE H^T were closely related to Bifidobacterium longum subsp. longum ATCC 15708^T with similarity values of 97.4% and 97.5%, respectively; TRI 7^T was closely related to Bifidobacterium tissieri DSM 100201 (96.0%). The Average Nucleotide Identity (ANI) and in silico DDH (isDDH) analysis with closest neighbour supported an independent phylogenetic position of all strains with values ranged from 74 to 85% for ANI and from 24 to 28% for isDDH. DNA base composition of the four strains was in the range of 58.3–63.5 mol% G + C. Based on the phylogenetic, genotypic and phenotypic data, the strains TRE 1^T, TRE D^T, TRE H^T and TRI 7^T clearly represent four novel taxa within the genus Bifidobacterium for which the names Bifidobacterium primatium sp. nov. (type strain TRE 1^T = DSM 100687^T = JCM 30945^T), Bifidobacterium scaligerum sp. nov. (type strain TRE D^T = DSM 103140^T = JCM 31792^T), Bifidobacterium felsineum sp. nov. (type strain TRE H^T = DSM 103139^T = JCM 31789^T) and Bifidobacterium simiarum sp. nov. (type strain TRI 7^T = DSM 103153^T = JCM 31793) are proposed.     

Integrated Analysis Identifies Molecular Signatures and Specific Prognostic Factors for Different Gastric Cancer Subtypes

BACKGROUND: Gastric cancer (GC) is the fifth leading cause of cancer-related deaths worldwide. As an effective and easily performed method, microscopy-based Lauren classification has been widely accepted by gastrointestinal surgeons and pathologists for GC subtyping, but molecular characteristics of different Lauren subtypes were poorly revealed. METHODS: GSE62254 was used as a derivation cohort, and GSE15459 was used as a validation cohort. The difference between diffuse and intestinal GC on the gene expression level was measured. Gene ontology (GO) enrichment analysis was performed for both subgroups. Hierarchical clustering and heatmap exhibition were also performed. Kaplan-Meier plot and Cox proportional hazards model were used to evaluate survival grouped by the given genes or hierarchical clusters. RESULTS: A total of 4598 genes were found differentially expressed between diffuse and intestinal GC. Immunity- and cell adhesion–related GOs were enriched for diffuse GC, whereas DNA repair– and cell cycle–related GOs were enriched for intestinal GC. We proposed a 40-gene signature (χ² = 30.71, P < .001) that exhibits better discrimination for prognosis than Lauren classification (χ² = 12.11, P = .002). FRZB [RR (95% CI) = 1.824 (1.115-2.986), P = .017] and EFEMP1 [RR (95% CI) = 1.537 (0.969-2.437), P = .067] were identified as independent prognostic factors only in diffuse GC but not in intestinal GC patients. KRT23 [RR (95% CI) = 1.616 (0.938-2.785), P = .083] was identified as an independent prognostic factor only in intestinal GC patients but not in diffuse GC patients. Similar results were achieved in the validation cohort. CONCLUSION: We found that GCs with different Lauren classifications had different molecular characteristics and identified FRZB, EFEMP1, and KRT23 as subtype-specific prognostic factors for GC patients.     

Induction Chemotherapy Has No Prognostic Value in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma and Chronic Hepatitis B Infection in the IMRT Era

BACKGROUND: The effectiveness of induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) over CCRT alone in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) and chronic hepatitis B infection in the intensity-modulated radiotherapy (IMRT) era is unknown. PATIENTS AND METHODS: A total of 249 patients with stage T1-2 N2-3 or T3-4 N1-3 NPC and chronic hepatitis B infection treated with IMRT were retrospectively reviewed. Propensity score matching (PSM) was employed to balance covariates; 140 patients were propensity-matched (1:1 basis). Survival outcomes in the IC + CCRT and CCRT groups were compared using the Kaplan–Meier method, log-rank test and Cox proportional hazards model. RESULTS: No significant survival differences were observed between IC + CCRT and CCRT (5-year overall survival, 88.3% vs. 82.2%; P = .484; disease-free survival, 73.9% vs. 75.2%; P = .643; distant metastasis-free survival, 84.1% vs. 85.1%; P = .781; and locoregional failure-free survival, 87.9% vs. 85.1%; P = .834). After adjusting for known prognostic factors in multivariate analysis, IC was not an independent prognostic factor for any outcome (all P > .05); subgroup analysis based on T category (T1-2/T3-4), N category (N0-1/N2-3), and overall stage (III/IV) confirmed these results. The incidence of hepatic function damage in the IC + CCRT and CCRT groups was not significantly different. CONCLUSION: IC + CCRT leads to comparable survival outcomes and hepatic function damage compared to CCRT alone in patients with locoregionally advanced NPC with chronic hepatitis B infection in the IMRT era. Further investigations are warranted.