Downregulation of enhancer RNA EMX2OS is associated with poor prognosis in kidney renal clear cell carcinoma.

Enhancer RNAs are a subclass of long non-coding RNAs transcribed from enhancer regions that play an important role in the transcriptional regulation of genes. However, their role in kidney renal clear cell carcinoma (KIRC) is largely unknown. Herein, we identified the key enhancer RNAs in KIRC via an integrated data analysis method. Gene expression profiles and clinical data of KIRC and 32 other cancer types were acquired using the University of California Santa Cruz Xena platform. Reported enhancer RNAs and genes regulated by them were selected as putative enhancer RNA-target pairs. Kaplan-Meier survival and correlation analyses were performed to identify the key enhancer RNAs. Finally, EMX2OS was identified as the enhancer RNA most associated with survival, with EMX2 as its target. EMX2OS downregulation was significantly associated with higher histological grade, advanced stage, and poorer prognosis. The results were validated in pan-cancer data from The Cancer Genome Atlas and RT-qPCR analysis of 12 pairs of KIRC and normal real-world samples. Functional enrichment analysis indicated that several metabolism-associated signaling pathways were enriched. This study demonstrated that EMX2OS is a key metabolism-associated enhancer RNA in KIRC with a favorable impact on survival and may be a novel therapeutic target in KIRC.

Expression of PD-L1 in tumor-associated nerves correlates with reduced CD8+ tumor-associated lymphocytes and poor prognosis in prostate cancer.

To investigate immune profile consisting of stromal PD-L1 expression, inhibitory or non-T-cell inflamed tumor microenvironment that may predict response to anti-PD-L1/PD-1 immunotherapy in prostate cancer, we validated the specificity of a PD-L1 monoclonal antibody (E1L3N) and identified PD-L1 specific expression in prostatic stromal nerve cells. PD-L1 expression was analyzed in 73 primary prostate cancers and 7 castration-resistant prostate cancers (CRPC) by immunohistochemistry (IHC) and resulting data from primary prostate cancers were correlated with tumor-associated lymphocytes (TALs), clinicopathological characteristics and clinical outcome. PD-L1 was expressed in the tumor cells in only one primary prostate cancer case and none of the CRPC. However, PD-L1 was frequently observed in the nerve branches in the tumor-associated stroma (69 of 73 cases, 94.5%), supported by colocalization with axonal marker PGP9.5. FoxP3-, CD3- and CD8-positive T lymphocytes were observed in 74.6% (47/63), 98.4% (62/63) and 100% (61/61) of the cases, respectively. The density of PD-L1+ tumor-associated nerves (TANs) was inversely correlated with that of CD8+ TALs. Higher density of PD-L1+ TANs was significantly associated with biochemical recurrence (BCR) in Kaplan-Meier survival analysis (p = 0.016). In both univariate and multivariate Cox analysis, the density of PD-L1+ TANs was independently prognostic of BCR. In conclusion, PD-L1 expression is rare in prostate tumor cells but prevalent in TANs and negatively correlated with CD8+ TALs. Neuro-immunological interaction may be a contribution to immune-suppressive microenvironment. Combinatorial treatment regimen designs to neural PD-L1 and TALs should be warranted in future clinical application of anti-PD-L1/PD-1 immunotherapy in prostate cancer.

Early Assessment of Right Ventricular Function in Systemic Lupus Erythematosus Patients using Strain and Strain Rate Imaging / Avaliação Precoce da Função Ventricular Direita em Pacientes com Lúpus Eritematoso Sistêmico pelo Strain e Strain Rate

Abstract Background: Right ventricular function is a crucial factor of the prognosis of systemic lupus erythematosus (SLE). Objectives: To evaluate the right ventricular function in SLE patients with different degrees of pulmonary hypertension (PH) by strain and strain rate imaging. Methods: A total of 102 SLE patients and 30 healthy volunteers were studied between October 2015 and May 2016. Patients were divided into three groups according to pulmonary artery systolic pressure (PASP) estimated by echocardiography: group control (A); PASP ≤ 30 mmHg (group B, n = 37); PASP 30-50 mmHg (mild PH; group C, n = 34); and PASP ≥ 50 mmHg (moderate-to-severe PH; group D, n = 31). Longitudinal peak systolic strain (ε) and strain rate (SR), including systolic strain rate (SRs), early diastolic strain rate (SRe) and late diastolic strain rate (SRa) were measured in the basal, middle and apical segments of the right ventricular free wall in participants by two-dimensional speckle tracking echocardiography (2D-STE) from the apical four-chamber view. A p < 0.05 was set for statistical significance. Results: The parameters of ε, SRs, SRe, and SRa were significantly decreased in groups C and D compared with groups A and B. The ε of each segments was significantly lower in group D than in group C, while there were no differences in SRs, SRe and SRa between groups C and D. Conclusions: Strain and strain rate imaging could early detect the right ventricular dysfunction in SLE patients with PH, and provide important value for clinical therapy and prognosis of these patients. (Arq Bras Cardiol. 2018; [online].ahead print, PP.0-0)

Resumo Fundamento: A função ventricular direita é fator crucial do prognóstico do lúpus eritematoso sistêmico (LES). Objetivos: Avaliar a função ventricular direita em pacientes com LES e diferentes graus de hipertensão pulmonar (HP) por avaliação do strain e do strain rate. Métodos: Um total de 102 pacientes com LES e 30 voluntários sadios foram estudados entre outubro de 2015 e maio de 2016. Os pacientes foram divididos em três grupos de acordo com a pressão sistólica da artéria pulmonar (PSAP) estimada por ecocardiografia: grupo controle (A); PSAP ≤ 30 mmHg (grupo B, n = 37); PSAP 30-50 mmHg (HP leve; grupo C, n = 34); e PSAP ≥ 50 mmHg (HP moderada a grave; grupo D, n = 31). Foram medidos, nos segmentos basal, medial e apical da parede livre do ventrículo direito, o pico sistólico longitudinal (ε) e o strain rate (SR), incluindo o SR sistólico (SRs), o SR diastólico precoce (SRp) e o SR diastólico tardio (SRt) pela técnica de ecocardiografia bidimensional com rastreamento de "pontos" (two-dimensional speckle tracking echocardiography, 2D-STE) pela visualização apical de quatro câmaras. Um p < 0,05 foi adotado como estatisticamente significativo. Resultados: Os parâmetros ε, SRs, SRp e SRt foram significativamente menores nos grupos C e D em comparação aos grupos A e B. O ε de cada segmento foi significativamente menor no grupo D que no grupo C, ao passo que não houve diferença no SRs, SRp ou SRt entre os grupos C e D. Conclusões: O strain e o SR obtidos por 2D-STE puderam detectar precocemente disfunção ventricular direita em pacientes com LES e HP, contribuindo para o tratamento clínico e prognóstico desses pacientes. (Arq Bras Cardiol. 2018; [online].ahead print, PP.0-0)

Early Assessment of Right Ventricular Function in Systemic Lupus Erythematosus Patients using Strain and Strain Rate Imaging.

BACKGROUND: Right ventricular function is a crucial factor of the prognosis of systemic lupus erythematosus (SLE). OBJECTIVES: To evaluate the right ventricular function in SLE patients with different degrees of pulmonary hypertension (PH) by strain and strain rate imaging. METHODS: A total of 102 SLE patients and 30 healthy volunteers were studied between October 2015 and May 2016. Patients were divided into three groups according to pulmonary artery systolic pressure (PASP) estimated by echocardiography: group control (A); PASP ≤ 30 mmHg (group B, n = 37); PASP 30-50 mmHg (mild PH; group C, n = 34); and PASP ≥ 50 mmHg (moderate-to-severe PH; group D, n = 31). Longitudinal peak systolic strain (ε) and strain rate (SR), including systolic strain rate (SRs), early diastolic strain rate (SRe) and late diastolic strain rate (SRa) were measured in the basal, middle and apical segments of the right ventricular free wall in participants by two-dimensional speckle tracking echocardiography (2D-STE) from the apical four-chamber view. A p < 0.05 was set for statistical significance. RESULTS: The parameters of ε, SRs, SRe, and SRa were significantly decreased in groups C and D compared with groups A and B. The ε of each segments was significantly lower in group D than in group C, while there were no differences in SRs, SRe and SRa between groups C and D. CONCLUSIONS: Strain and strain rate imaging could early detect the right ventricular dysfunction in SLE patients with PH, and provide important value for clinical therapy and prognosis of these patients. (Arq Bras Cardiol. 2018; [online].ahead print, PP.0-0).

Assessment of Right Atrium Function in Patients With Systemic Lupus Erythematosus With Different Pulmonary Artery Systolic Pressures by 2-Dimensional Speckle-Tracking Echocardiography.

OBJECTIVES: To assess right atrium (RA) function of patients with systemic lupus erythematosus (SLE) and pulmonary artery hypertension (PAH) by 2-dimensional speckle-tracking echocardiography. METHODS: Thirty matched healthy adults were selected as group A. Then, 102 patients with SLE were divided into 3 groups according to the severity of PAH. Group B included 37 patients without PAH (pulmonary artery [PA] systolic pressure ≤ 30 mm Hg); group C included 34 patients with PAH (PA systolic pressure of 30-50 mm Hg); and group D included 31 patients with PAH (PA systolic pressure ≥ 50 mm Hg). Parameters evaluated included RA maximum volume, minimum volume, preatrial contraction volume, passive ejection fraction (EF), and active EF. The global peak longitudinal systolic strain rate and early and late diastolic strain rates of the RA were obtained by 2-dimensional speckle-tracking echocardiography. RESULTS: No significant differences were found in all parameters between groups B and A (P > .05). The RA maximum volume, minimum volume, preatrial contraction volume, active EF, and late diastolic strain rate in groups C and D were significantly increased compared with those in groups A and B, and the parameters in group D were significantly higher than those in group C (P < .05). Although the RA passive EF, early diastolic strain rate, and systolic strain rate in groups C and D were significantly decreased compared with those in groups A and B, those in group D were significantly lower than those in group C (P < .05). CONCLUSIONS: Two-dimensional speckle-tracking echocardiography could effectively assess RA function in patients with SLE who have different severities of PAH.