RADIOMICS BASED ON TWO-DIMENSIONAL AND THREE-DIMENSIONAL ULTRASOUND FOR EXTRATHYROIDAL EXTENSION FEATURE PREDICTION IN PAPILLARY THYROID CARCINOMA.

Aim: To evaluate the diagnostic performance of radiomics features of two-dimensional (2D) and three-dimensional (3D) ultrasound (US) in predicting extrathyroidal extension (ETE) status in papillary thyroid carcinoma (PTC). Patients and Methods: 2D and 3D thyroid ultrasound images of 72 PTC patients confirmed by pathology were retrospectively analyzed. The patients were assigned to ETE and non-ETE. The regions of interest (ROIs) were obtained manually. From these images, a larger number of radiomic features were automatically extracted. Lastly, the diagnostic abilities of the radiomics models and a radiologist were evaluated using receiver operating characteristic (ROC) analysis. We extracted 1693 texture features firstly. Results: The area under the ROC curve (AUC) of the radiologist was 0.65. For 2D US, the mean AUC of the three classifiers separately were: 0.744 for logistic regression (LR), 0.694 for multilayer perceptron (MLP), 0.733 for support vector machines (SVM). For 3D US they were 0.876 for LR, 0.825 for MLP, 0.867 for SVM. The diagnostic efficiency of the radiomics was better than radiologist. The LR model had favorable discriminate performance with higher area under the curve. Conclusion: Radiomics based on US image had the potential to preoperatively predict ETE. Radiomics based on 3D US images presented more advantages over radiomics based on 2D US images and radiologist.

The inhibition of the breast cancer by PPARγ agonist pioglitazone through JAK2/STAT3 pathway.

Breast cancer, especially triple-negative breast cancer, is one of the deadliest cancers in women. To date, there is a lack of a good therapeutic regimen for it. PPARγ has been reported to be a tumor suppressor and could be activated by many agonists involved in cancer inhibition. Therefore, the expression of PPARγ in breast cancer was analyzed by online software UALCAN whose data were from the TCGA database. The results revealed that the PPARγ expression was reduced in breast cancer tissues. Furthermore, the methylation in the PPARγ promoter was also assayed and the results indicated that the methylation level in the PPARγ promoter in breast cancer tissue was higher than that in normal tissue. In order to verify the methylation in promoter involved in the regulation of gene PPARγ expression, the 5'-Aza and fluorescence assays were performed and the results proved that methylation in promoter participated in gene PPARγ expression regulation. Pioglitazone, a PPARγ agonist, still was not investigated in breast cancer. Therefore, the effects of pioglitazone on breast cancer cells were tested by cell viability, scratch and transwell assays, and results indicated that the pioglitazone has the inhibition effect on the proliferation and migration of breast cancer cells by PPARγ which was correlated with the JAK2/STAT3 pathway. In order to further confirm the inhibition effect of pioglitazone on breast cancer in vivo, the nude mice model was administrated by gavage with pioglitazone. And the results indicated that pioglitazone could inhibit the growth of breast cancer in the PPARγ overexpression group in vivo. In summary, the expression of gene PPARγ was decreased in breast cancer tissues, which was correlated with its methylation in the promoter region. Moreover, pioglitazone could exert its inhibition on breast cancer proliferation and migration by the JAK2/STAT3 pathway.

Association of SNPs in PLA2R1 with idiopathic and secondary membranous nephropathy in two Chinese cohorts.

Objectives: Specific single-nucleotide polymorphisms (SNPs) in the M-type phospholipase A2 receptor-1 (PLA2R1) are associated with increased risk of idiopathic membranous nephropathy (IMN) in European populations. We hypothesized links between IMN and SMN with these SNPs in two Chinese cohorts.Methods: A cohort of 166 IMN patients and 144 controls from southern China (Group A) and a cohort of 212 IMN patients, 118 SMN patients, and 162 controls from northwestern China (Group B) were recruited. SNPs within PLA2R1 (rs3749119, rs3749117, rs35771982, rs3828323, and rs4664308) were identified and the frequencies of genotypes and alleles were determined for the different groups.Results: Relative to controls, IMN patients had a greater prevalence of rs35771982, rs3749117, and rs4664308 in Group A (OR = 1.61, 95% CI = 1.13-2.31, P = 0.011; OR = 1.62 (1.15-2.29), P = 0.006 and OR = 1.17 (1.06-1.28), P = 0.001, respectively) and in Group B (OR = 1.58 (1.13-2.22), P = 0.009; OR = 1.68 (1.22-2.33), P = 0.002 and OR = 1.15 (1.06-1.25), P < 0.001, respectively). Genotype and allele distributions of rs4664308 differed significantly between SMN patients and controls in Group B (OR = 1.58 (1.10-2.26), P = 0.012). Genotype and allele distribution of rs35771982 and rs4664308 differed significantly between PLA2R-Ab(+) and PLA2R-Ab(-) IMN patients in Group B (OR = 1.59 (1.09-2.31), P = 0.018 and OR = 1.15 (1.03-1.29), P = 0.005, respectively).Conclusion: This study of two cohorts from different regions of China indicate that specific PLA2R1 polymorphisms are associated with IMN and SMN.

Expression of IncRNA UCA1 in ovarian cancer and its clinical significance.

OBJECTIVES: To explore the expression and clinical significance of IncRNA-UCA1 in ovarian cancer. MATERIALS AND METHODS: The ex- pression of IncRNA-UCA1 in 26 ovarian cancer tissue and 16 normal and benign ovarian tissue were detected using qRT-PCR method, and the correlation of expression level with clinicopathological features were analyzed. RESULTS: Higher lncRNA-UCA1 expression level were detected in ovarian cancer tissue than those in normal ovarian tissue (p < 0.05). There were significant correlations between higher expression of IncRNA-UCA1 with tumor staging (p = 0.000), histological grades (p = 0.000), peritoneal effusion (p = 0.001), and lymph node metastasis (p = 0.000), but not with age. CONCLUSION: IncRNA-UCA1 may play a vital role in the metastasis of ovarian cancer and it is expected to be a potential novel biomarker and therapeutic target of ovarian cancer.

Validation of associations between ESR1 variants and breast cancer risk in Chinese cohorts.

Estrogen receptor-a (ER) protein plays a key role in breast carcinogenesis, and common genetic variants in the corresponding gene locus have been associated with breast cancer risk in different populations. Here, we analyzed estrogen receptor 1 (ESR1) associations in two hospital-based studies of patients from the south of China. Three single-nucleotide polymorphisms (SNPs; rs3757318, rs2046210, and rs3734805) in ESR1 were selected from previous genome-wide association study results and were genotyped using the Sequenom MassARRAY® iPLEX System in 845 breast cancer patients and 882 healthy controls. Association analysis based on unconditional logistic regression was carried out to determine the odds ratio (OR) and 95% confidence interval (95%CI) for each SNP. Stratified analyses according to the status of ER and progesterone receptor (PR) were also performed. Of the three SNPs, rs3757318 did not pass the Hardy-Weinberg equilibrium test and was excluded from the subsequent analysis. The other two SNPs (rs2046210 and rs3734805) were strongly associated with susceptibility to breast cancer. Allele T of rs2046210 and allele C of rs3734805 were risk alleles and the adjusted ORs were 1.348 (95%CI = 1.172-1.550, P = 0.0001) and 1.319 (95%CI = 1.144-1.522, P = 0.0001), respectively. Furthermore, the risk allele of rs2046210 gave negative results for ER and PR expression in an immunohistochemical test, with ORs of 0.602 (95%CI = 0.384-0.944, P = 0.027) and 0.532 (95%CI = 0.338-0.837, P = 0.006), respectively. Our study further supports associations between rs2046210 and rs3734805 and breast cancer risk in Chinese women.

Increased IL-17 and IL-21 producing TCRαß+CD4-CD8- T cells in Chinese systemic lupus erythematosus patients.

BACKGROUND: Increased numbers of TCRαß(+)CD4(-)CD8(-) T cells in the peripheral blood of systemic lupus erythematosus (SLE) patients in the United States and United Kingdom have been reported. However, the proportions of TCRαß(+)CD4(-)CD8(-) T cells and their involvement in the pathogenesis of SLE in Chinese populations are yet to be determined. METHODS: A total of 120 SLE patients, 38 rheumatoid arthritis (RA) patients and 43 normal control subjects were examined. The proportion of TCRαß(+)CD4(-)CD8(-) T cells in the peripheral blood, Fas expression on these cells, and intracellular cytokine levels in these cells were assessed using flow cytometry. Plasma cytokine concentrations were measured using enzyme-linked immunosorbent assay. RESULTS: The percentages of TCRαß(+)CD4(-)CD8(-) T cells were increased in Chinese SLE patients, particularly in active SLE patients, correlated with decreased Fas expression on these cells. IL-17 and IL-21 levels in the blood and in TCRαß(+)CD4(-)CD8(-) T cells from SLE patients were increased. Moreover, a positive correlation was evident between IL-17- and IL-21-producing TCRαß(+)CD4(-)CD8(-) T cells. CONCLUSIONS: Increased TCRαß(+)CD4(-)CD8(-) T cells expressing inflammatory cytokines, such as IL-17 and IL-21, may be implicated in the pathogenesis of SLE in patients. Appropriate IL-17- and/or IL-21 blockage may be utilized as a novel immunotherapeutic strategy for SLE patients.