LncRNA CRNDE facilitates epigenetic suppression of CELF2 and LATS2 to promote proliferation, migration and chemoresistance in hepatocellular carcinoma.

Our study aimed to investigate the expression, functional significance, and related mechanism of long noncoding RNA CRNDE (colorectal neoplasia differentially expressed) in hepatocellular carcinoma (HCC) pathogenesis. The resulted revealed that CRNDE was significantly overexpressed in HCC tissues and cell lines, and was statistically correlated with poor clinical outcome. CRNDE knockdown markedly decreased HCC cell proliferation, migration, and chemoresistance. In addition, in vivo experiments confirmed the suppressive effect of CRNDE knockdown on HCC progression. Mechanically, CRNDE directly bound to EZH2 (enhancer of zeste homolog), SUZ12 (suppressor of zeste 12), SUV39H1, and mediated their inhibition of tumor suppressor genes, including CUGBP Elav-like family member 2 (CELF2) and large tumor suppressor 2 (LATS2). CELF2 exerted tumor suppressive effect in HCC and was involved in CRNDE-mediated oncogenic effect. In addition, the oncogenic effects of CRNDE on HCC proliferation, migration and tumorigenesis, as well as its inhibition of Hippo pathway were abolished by LATS2 overexpression. Together, our work demonstrated the importance of CRNDE in HCC progression and elucidated the underlying molecular mechanisms. These findings provided new insights into HCC pathogenesis and chemoresistance mediated by CRNDE.

A Nomogram Based on a TRUS Five-Grade Scoring System for the Prediction of Prostate Cancer and High Grade Prostate Cancer at Initial TRUS-Guided Biopsy.

Purpose: To evaluate the efficacy of transrectal ultrasound five-grade scoring system (TRUS-5) in predicting prostate cancer (PCa) and high grade PCa (HGPCa), compared with TRUS two-grade scoring system (TRUS-2), and establish a TRUS-5 based nomogram for the prediction of PCa and HGPCa at initial biopsy (IPBx). Methods: Data were collected from 862 men who underwent initial TRUS-guided 12-core prostate biopsy. Age, prostate-specific antigen (PSA), percent free PSA, digital rectal examination (DRE), prostate volume (PV), PSA density (PSAD) and TRUS findings were included in the analysis. For TRUS-5, the probability of PCa was quantified on a scale from 1 (benign) to 5 (malignant). TRUS-2 used the grades "normal" and "suspicious". After univariate and multivariate logistic regression analyses, nomogram models were developed and internally validated based on independent predictors to predict the probability of PCa and HGPCa. Results: Overall PCa was detected in 42% (362/862) with 26.22% (226/862) showing HGPCa. TRUS-5 significantly outperformed TRUS-2 for the risk prediction of PCa and HGPCa (area under the receiver operating characteristic curve [AUC]: 0.787 vs. 0.694 for PCa, 0.841 vs. 0.713 for HGPCa, P<0.05). The TRUS-5 based nomogram showed higher AUCs (0.905 for PCa, 0.903 for HGPCa) than PSA alone, clinical base model, the TRUS-2 based model, and other predictive models (P<0.05). Conclusions: TRUS-5 represents a better imaging predictor than TRUS-2 for PCa and HGPCa. Our TRUS-5 based nomogram models performed well for the prediction of PCa and HGPCa at IPBx, which may help to make the decision to biopsy.

The utility and limitations of contrast-enhanced transrectal ultrasound scanning for the detection of prostate cancer in different area of prostate.

OBJECTIVE: To evaluate the ability of contrast-enhanced transrectal ultrasound (CETRUS) scanning for prostate cancer detection in different area, compared with conventional transrectal ultrasound (TRUS). METHODS: 228 patients underwent TRUS-guided prostate biopsy after examinations of TRUS and CETRUS scanning. Cancer detection between CETRUS and TRUS were compared by patient and by site in different areas (right, left; base, mid-gland, apex). The receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic performance of CETRUS. RESULTS: 89 patients were malignant and 48 patients were significant cancer. Compared with TRUS, CETRUS could increase the detection rates of overall and significant cancer (P = 0.008; P = 0.031). CETRUS had higher sensitivity, specificity (except right lobe), accuracy, positive predictive value (PPV) and negative predictive value (NPV) in total, right and left lobe (P < 0.05). The sensitivity were greater for CETRUS in all areas except left base and right apex (P < 0.05). The accuracy were greater for CETRUS in all areas except left mid-gland and right apex (P < 0.05). ROC analysis showed CETRUS totally got the AUC of 0.816. The AUC was higher in left lobe than right lobe (0.837 vs. 0.793). It was most accurate at the base (0.833), then mid-gland (0.826), and lowest in apex (0.772). CONCLUSIONS: CETRUS had a significant advantage over conventional TRUS for prostate cancer detection in different areas. CETRUS much more easily missed the cancer in apex, we must focus more on apex and may add other imaging modalities to improve the visualization and detection of prostate cancer.

Influence of serum prostate-specific antigen (PSA) level, prostate volume, and PSA density on prostate cancer detection with contrast-enhanced sonography using contrast-tuned imaging technology.

OBJECTIVES: The purpose of this study was to evaluate the influence of the serum prostate-specific antigen (PSA) level, prostate volume, and PSA density on prostate cancer detection with contrast-enhanced sonography using contrast-tuned imaging technology compared with baseline imaging (combination of grayscale and power Doppler imaging). METHODS: In all, 161 patients were evaluated with grayscale, power Doppler, and contrast-tuned imaging. Biopsy was performed at 10 sites in each patient. When an abnormality was shown on any of these examinations, the biopsy was directed toward the abnormality. Cancer detection between contrast-tuned imaging and baseline imaging was compared for different subgroups according to PSA level (4-10, 10-20, and >20 ng/mL), prostate volume (<35, 35-50, 50-65, and >65 mL), and PSA density (<0.15, 0.15-0.30, 0.30-0.50, and >0.50). RESULTS: In total, 413 sites were malignant in 78 patients. By biopsy site, the accuracy was greater for contrast-tuned imaging than for baseline imaging in all PSA level, prostate volume, and PSA density subgroups except 0.30 to 0.50 (all P < .05). Contrast-tuned imaging had significantly higher sensitivity in the subgroups with PSA levels between 4 and 20 ng/mL, prostate volumes between 35 and 65 mL, and PSA densities between 0.15 and 0.50 than baseline imaging (all P < .05); it also had significantly higher specificity for all PSA level subgroups except 10 to 20 ng/mL, all prostate volume subgroups except 35 to 50 mL, and all PSA density subgroups except 0.30 to 0.50 (all P < .05). CONCLUSIONS: Contrast-tuned imaging could improve cancer detection over baseline imaging in patients with different PSA levels, prostate volumes, and PSA densities.

Value of contrast-enhanced sonographic micro flow imaging for prostate cancer detection with t-PSA level of 4-10 ng/mL.

OBJECTIVES: To compare the efficiency of contrast-enhanced ultrasonographic micro flow imaging (MFI) with conventional transrectal ultrasound (TRUS) in detecting prostate cancer with serum total prostate-specific antigen (t-PSA) of 4.0-10.0 ng/mL. To evaluate the value of contrast-enhanced ultrasonographic MFI in detecting prostate cancer with t-PSA in diagnostic gray zone. METHODS: 47 patients with t-PSA 4.0-10.0 ng/mL underwent gray scale, power Doppler TRUS and MFI examinations before ultrasound guided biopsies. Biopsies were performed at twelve sites in the base, the mid-gland and the apex of the prostate in each patient, when there was no abnormal ultrasound finding. When an abnormality was present at MFI, the biopsy specimen from the corresponding site was directed toward the abnormal finding. With histological results of prostate biopsy as reference standards, we assessed the cancer detection of these three methods. RESULTS: 564 specimens were collected in this study, in which 101 were prostate cancer confirmed histologically. 152 of 564 specimens were demonstrated abnormal on MFI images, in which 71 were malignant and 81 were benign confirmed histologically. The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) for MFI in detecting prostate caner were 70.3%, 82.5%, 80.3%, 46.7% and 92.7%, respectively. The sensitivity and NPV for MFI were significantly better than gray scale (38.6%, 86.9%) and power Doppler (32.7%, 86.0%) (P<0.001) TRUS. CONCLUSIONS: Contrast-enhanced ultrasonographic MFI could significantly improve the detection rate of prostate cancer with t-PSA in diagnostic gray zone (4-10 ng/mL) than conventional ultrasound.

Contrast-enhanced ultrasonography with contrast-tuned imaging technology for the detection of prostate cancer: comparison with conventional ultrasonography.

UNLABELLED: Study Type - Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? The present study was to perform contrast-tuned imaging (CnTI) technology to detect prostate cancer and compare the use of CnTI technology for the detection of prostate cancer with conventional ultrasonography. The preliminary data from our study suggested that targeted biopsy of the prostate with CnTI technology could improve the cancer detection and detect higher grade prostate cancers. OBJECTIVES: To perform contrast-enhanced ultrasonography (CEUS) using contrast-tuned imaging (CnTI) technology to detect prostate cancer. To evaluate the detection of prostate cancer with CnTI compared with conventional grey-scale and power Doppler ultrasonography. PATIENTS AND METHODS: In all, 150 patients referred for prostate biopsy were evaluated using transrectal grey-scale, power Doppler and CnTI ultrasonography. Biopsy was performed at 10 sites in each patient. If an abnormality was found at any of these three ultrasonography examinations, a biopsy specimen was targeted towards from the corresponding site. The performances of the three ultrasonography techniques for prostate cancer detection were compared. RESULTS: Prostate cancer was detected at 383 sites from 73 patients. The combination of these three examinations detected more patients with prostate cancer than grey-scale (P= 0.002), power Doppler (P= 0.001) or baseline imaging (the combination of grey-scale and power Doppler; P= 0.031) alone. By biopsy site, CnTI had higher sensitivity and accuracy (73.1% and 83.7%) than grey-scale (50.9%; P < 0.001 and 78.8%; P < 0.001) or power Doppler (48.3%; P < 0.001 and 77.7%; P < 0.001), while the specificity was similar for grey-scale (88.4%), power Doppler (87.8%) and CnTI (87.3%; P > 0.05 in each case). CnTI had higher sensitivity (73.1% vs 62.9%; P < 0.001), specificity (87.3% vs 82.1%; P < 0.001) and accuracy (83.7% vs 77.2%; P < 0.001) than baseline imaging. The mean Gleason score of CnTI-positive cases was significantly higher than CnTI-negative cases (7.1 vs 6.3; P= 0.002). CONCLUSIONS: CEUS using CnTI technology enables a visualization of the microvasculature associated with prostate cancer. CnTI technology could be used to guide biopsy and improve the detection rate of prostate cancer. CnTI technology was able to detect higher grade prostate cancers.

Value of contrast-enhanced sonography with micro flow imaging in the diagnosis of prostate cancer.

BACKGROUND: To evaluate the effectiveness of contrast-enhanced sonographic micro flow imaging (MFI) in the diagnosis of prostate cancer. METHODS: A total of 74 patients referred for prostate biopsy were prospectively evaluated with MFI. The abnormalities were categorized into four patterns: pattern 1: indistinct separation between the inner and outer gland; pattern 2: asymmetrical or focally increased enhancement in the outer gland; pattern 3: enhancement with focal defect; pattern 4: enhancement in the outer gland equal to that of the inner gland. The findings were correlated with Gleason scores. RESULTS: Prostate cancer was detected in 264 sites in 41 patients. The sensitivity, specificity, accuracy, and positive and negative predictive values for MFI were 81.1%, 84.3%, 83.3%, 68.6%, and 91.3%, respectively. Positive predictive values for the four patterns were 46.0 (pattern 1), 53.6 (pattern 2), 94.3 (pattern 3), and 95.4 (pattern 4). Gleason scores of cancers with patterns 3 (7.09) or 4 (7.51) were significantly higher than those with patterns 1 (6.17) or 2 (6.59) (p = 0.001, p = 0.005, p < 0.001, p < 0.001). CONCLUSIONS: Some MFI patterns had high positive predictive values and were associated with more aggressive cancers. This could be used to reduce the number of biopsy sites and detect clinically significant cancers.