Value of magnetic resonance imaging radiomics features in predicting histologic grade of invasive ductal carcinoma of the breast.

BACKGROUND: Breast cancer has the second highest mortality rate of all cancers and occurs mainly in women. OBJECTIVE: To investigate the relationship between magnetic resonance imaging (MRI) radiomics features and histological grade of invasive ductal carcinoma (IDC) of the breast and to evaluate its diagnostic efficacy. METHODS: The two conventional MRI quantitative indicators, i.e. the apparent diffusion coefficient (ADC) and the initial enhancement rate, were collected from 112 patients with breast cancer. The breast cancer lesions were manually segmented in dynamic contrast-enhanced MRI (DCE-MRI) and ADC images, the differences in radiomics features between Grades I, II and III IDCs were compared and the diagnostic efficacy was evaluated. RESULTS: The ADC values (0.77 ± 0.22 vs 0.91 ± 0.22 vs 0.92 ± 0.20, F= 4.204, p< 0.01), as well as the B_sum_variance (188.51 ± 67.803 vs 265.37 ± 77.86 vs 263.74 ± 82.58, F= 6.040, p< 0.01), L_energy (0.03 ± 0.02 vs 0.13 ± 0.11 vs 0.12 ± 0.14, F= 7.118, p< 0.01) and L_sum_average (0.78 ± 0.32 vs 16.34 ± 4.23 vs 015.45 ± 3.74, F= 21.860, p< 0.001) values of patients with Grade III IDC were significantly lower than those of patients with Grades I and II IDC. The B_uniform (0.15 ± 0.12 vs 0.11 ± 0.04 vs 0.12 ± 0.03, F= 3.797, p< 0.01) and L_SRE (0.85 ± 0.07 vs 0.78 ± 0.03 vs 0.79 ± 0.32, F= 3.024, p< 0.01) values of patients with Grade III IDC were significantly higher than those of patients with Grades I and II IDC. All differences were statistically significant (p< 0.05). The ADC radiomics signature model had a higher area-under-the-curve value in identifying different grades of IDC than the ADC value model and the DCE radiomics signature model (0.869 vs 0.711 vs 0.682). The accuracy (0.812 vs 0.647 vs 0.710), specificity (0.731 vs 0.435 vs 0.342), positive predictive value (0.815 vs 0.663 vs 0.669) and negative predictive value (0.753 vs 0.570 vs 0.718) of the ADC radiomics signature model were all significantly better than the ADC value model and the DCE radiomics signature model. CONCLUSION: ADC values and breast MRI radiomics signatures are significant in identifying the histological grades of IDC, with the ADC radiomics signatures having greater value.

Circular RNA SMARCA5 Promotes a Poor Prognosis and Radiotherapy Resistance for Patients with Hepatocellular Carcinoma.

OBJECTIVE: The involvement of Circular RNA SMARCA5 (cSMARCA5) in several types of cancer has been reported; however, its role in hepatocellular carcinoma (HCC) is unclear. The presented research aimed to explore the expression level of cSMARCA5 in HCC tissues and evaluate the association between cSMARCA5, prognosis, and radiotherapy resistance for patients with HCC. METHODS: This study was designed as a case controlled study and enrolled 106 HCC patients. HCC and paired non-tumor samples were collected from HCC patients. Gene expression was analyzed by RT-qPCR. The association between the expression level of cSMARCA5 and prognosis value and radiotherapy resistance for patients with HCC was analyzed by Kaplan-Meier survival curve and Multivariate Cox analysis. RESULTS: Compared to paracancerous tissue, cSMARCA5 demonstrated higher expression in the tumor tissues (p<0.0001).Higher expression of cSMARCA5 is a risk factor in 3-year overall survival (OS) for HCC patients (HR=1.798, 95%CI: 1.165~3.231, p=0.0321). Multivariate analysis showed that higher expression of cSMARCA5 was related to PVTT (HR=2.136, 95%CI: 1.130~5.218), AFP (>400ng/ml) (HR=2.335, 95%CI: 1.247~5.661), tumor size (>5cm) (HR=3.017, 95%CI: 1.477~5.659), poor histopathologic grading (HR=3.344, 95%CI: 2.175~6.143), and multiple tumor number (HR=2.875, 95%CI: 1.453~3.884). We also found that radiotherapy resistance was related to AFP (>400ng/ml) (OR=2.125, 95%CI: 1.015~3.348), tumor size (>5cm) (OR=2.857, 95%CI: 1.665~4.978), poor histopathologic grading (OR=2.463, 95%CI: 1.389~4.446), multiple tumor number (OR=2.332, 95%CI: 1.538~3.887), and high expression of cSMARCA5 (OR=3.574, 95%CI: 1.663~5.932). CONCLUSION: CircRNA-SMARCA5 is significantly increased in HCC tissues and promotes radiotherapy resistance. More importantly, higher expression level of cSMARCA5 is related to a poorer 3-year OS for patients with HCC.

Correlation analyses of thyroid-stimulating hormone and thyroid autoantibodies with differentiated thyroid cancer.

PURPOSE: To investigate the feasibilities and clinical values of thyroid-stimulating hormone (TSH) and thyroid autoantibodies in predicting differentiated thyroid cancer (DTC). METHODS: 500 patients with thyroid nodules who underwent surgery for the first time in our hospital from January 2014 to December 2016 were selected, including 250 patients definitely diagnosed pathologically with DTC and 250 patients definitely diagnosed with benign thyroid nodules after operation. Serum thyroglobulin antibody (TgAb), thyroid peroxidase antibody (TPOAb) and TSH levels before operation were evaluated in both groups. According to the reference ranges of TgAb and TPOAb, they were divided into negative and positive groups. According to the TSH reference range, they were divided into decreased, normal and increased groups. Statistical analyses were conducted, respectively. RESULTS: The serum TgAb level in the DTC group was significantly increased compared with that in benign thyroid nodule group (p=0.01). The positive rate of TgAb in DTC group was also significantly higher than that in benign thyroid nodule group (p<0.01). The level of serum TPOAb in the DTC group was not significantly different from that in the benign thyroid nodule group (p=0.25). The level of serum TSH in the DTC group was significantly increased compared with that in the benign thyroid nodule group (p<0.01). There was a statistically significant difference in the comparison of the distribution of TSH between the DTC group and benign thyroid nodule group (p<0.01). Univariate analysis showed that TgAb and TSH were correlated with DTC. Multivariate logistic regression analysis results showed that serum positive TgAb and increased TSH wre significantly correlated with DTC. TSH level in DTC with cervical lymph node metastasis group was significantly increased compared with DTC without such metastasis group (p<0.01). CONCLUSIONS: Increased levels of serum TgAb and TSH may be risk factors for DTC. Whether the two indicators can be used as predictors of DTC screening needs to be confirmed in large-sample prospective trials. Increased serum TSH level is closely related to DTC with cervical lymph node metastasis.

microRNA­145 modulates migration and invasion of bladder cancer cells by targeting N­cadherin.

MicroRNA (miRNA)­145 has been demonstrated to serve a role in several types of tumors, however, the potential molecular mechanism of action of miRNA­145 in bladder cancer metastasis remains to be elucidated. This study aimed to investigate the potential modulation of miRNA­145 in bladder carcinoma and elucidate the underlying molecular mechanism. The expression of miRNA­145 in bladder adenocarcinoma tissues and bladder cancer cells was measured by reverse transcription­quantitative polymerase chain reaction. miRNA­145 mimics and inhibitor were transfected into bladder cancer (BC) cells to determine the role of miRNA­145 on cell motility and invasion measured by wound healing and transwell assays. Luciferase assay was performed to confirm whether N­cadherin was the direct target of miRNA­145. Subsequently, expression of N­cadherin and matrix metalloproteinase­9 (MMP9) in BC cells were detected by western blot analysis. miRNA­145 was significantly downregulated cells and tissues from patients with BC, compared with healthy controls. miRNA­145 markedly inhibited the ability of BC cells to migrate and invade. Furthermore, N­cadherin was identified as a target of miRNA­145 in BC cells. MMP9, acting downstream of N­cadherin, was downregulated in BC cells by miRNA­145. In the present study, miRNA­145 suppressed the migration and invasion of BC cells by regulating N­cadherin. The results of the present study indicated that miRNA­145 may function as a tumor suppressor and may have a potential to be a diagnostic and predictive biomarker, and a therapeutic target for treatment of BC.

Differential Diagnosis of Benign and Malignant Breast Tumors Using Apparent Diffusion Coefficient Value Measured Through Diffusion-Weighted Magnetic Resonance Imaging.

OBJECTIVE: Apparent diffusion coefficient (ADC) value measurement of nodes in diffusion-weighted imaging was widely used in differentiating different types of human tumors. The aim of this meta-analysis was to evaluate the clinical value of ADC measurement through diffusion-weighted magnetic resonance imaging (DW-MRI) in the differential diagnosis of benign and malignant breast tumors. METHODS: Relevant studies were identified through computer-based search of databases, which were supplemented through manual search strategies. Case-control studies were selected in adherence with our strict inclusion and exclusion criteria. Statistical analysis was conducted using Stata 12.0 statistical software (StataCorp, College Station, Tex). RESULTS: Our database searches initially retrieved 602 studies (320 studies in Chinese and 282 studies in English), and 31 studies (18 studies in English and 13 studies in Chinese) were eventually selected for meta-analysis. These 31 case-control studies included a total of 926 normal breast tissues and 2323 breast tumors (911 benign tumors and 1412 malignant tumors). Our meta-analysis showed that ADC values measured through DW-MRI were higher in benign breast tumors compared with malignant breast tumors, and this difference was statistically significant. In addition, the ADC values in the normal breast tissues were markedly higher than the benign breast tumors, which were also at a statistically significant level. Consistent with these observations, the ADC values in the normal breast tissues were significantly higher when compared with the values found in the malignant breast tumors. CONCLUSIONS: Our data strongly support the conclusion that the ADC value measured through DW-MRI is an important radiographic index for differential diagnosis of benign and malignant breast tumors and is critical to our assessment of the internal structure of tumors.

Dual PI3K/mTOR inhibitor NVP-BEZ235-induced apoptosis of hepatocellular carcinoma cell lines is enhanced by inhibitors of autophagy.

Dysregulation of the phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling has been found in several types of human cancer, including hepatocellular carcinoma (HCC). NVP-BEZ235 is a novel, orally bioavailable dual PI3K/mTOR inhibitor that has exhibited promising activity against HCC in preclinical models. Autophagy is a cellular lysosomal degradation pathway essential for the regulation of cell survival and death to maintain homeostasis. This process is negatively regulated by mTOR signaling and often counteracts the efficacy of certain cancer therapeutic agents. In this study, we explored the role of autophagy in apoptosis induced by NVP-BEZ235 in two HCC cell lines, Hep3B and PLC/PRF/5, and identified the mechanism of combinatorial treatment. NVP-BEZ235 was effective in inhibiting the growth of the two HCC cell lines possibly though induction of apoptosis. NVP-BEZ235 also potently increased the expression of LC3-II and decreased the expression of p62, indicating induction of autophagy. When NVP-BEZ235 was used in combination with Atg5 siRNA or the autophagy inhibitor 3-methyladenine (3-MA), enhancement of the inhibitory effects on the growth of HCC cells was detected. In addition, enhanced induction of apoptosis was observed in cells exposed to the combination of NVP-BEZ235 and Atg5 siRNA or 3-MA. Thus, induction of autophagy by NVP-BEZ235 may be a survival mechanism that counteracts its anticancer effects. Based on these data, we suggest a strategy to enhance the anticancer efficacy of BEZ235 by blockade of autophagy. Thus, our study provides a rationale for the clinical development of combinations of NVP-BEZ235 and autophagy inhibitors for the treatment of HCC and other malignancies.