This study aims to predict expression of estrogen receptor (ER) in breast cancer by radiomics. Firstly, breast cancer images are segmented automatically by phase-based active contour (PBAC) method. Secondly, high-throughput features of ultrasound images are extracted and quantized. A total of 404 high-throughput features are divided into three categories, such as morphology, texture and wavelet. Then, the features are selected by R language and genetic algorithm combining minimum-redundancy-maximum-relevance (mRMR) criterion. Finally, support vector machine (SVM) and AdaBoost are used as classifiers, achieving the goal of predicting ER by breast ultrasound image. One hundred and four cases of breast cancer patients were conducted in the experiment and optimal indicator was obtained using AdaBoost. The prediction accuracy of molecular marker ER could achieve 75.96% and the highest area under the receiver operating characteristic curve (AUC) was 79.39%. According to the results of experiment, the feasibility of predicting expression of ER in breast cancer using radiomics was verified.
ObjectiveTo detect protein expression of androgen receptor (AR) in patients with estrogen receptor (ER)-positive primary breast cancer and investigate its significances on prognosis.MethodsThe clinicopathologic data of female patients with ER-positive primary breast cancer in the Affiliated Hospital of Southwest Medical University from January 2012 to December 2012 were retrospectively analyzed. The AR protein expression in the breast cancer tissue was detected by the immunohistochemistry. The relationship between the AR protein expression and the clinicopathologic characteristics such as the age, tumor diameter, invasive biological behavior, molecular typing or the survival after the operation was analyzed.ResultsThe positive rate of AR protein expression was 58.5% (76/130) in the patients with ER-positive primary breast cancer. The positive rates of AR protein expression in the patients with the low differentiation, clinical stage Ⅲ+Ⅳ, p53 positive, neurovascular invasion, and lymph node metastasis were significantly lower than those in the patients with the moderate and high differentiations, clinical stage Ⅰ +Ⅱ, p53 negative, without neurovascular invasion, and without lymph node metastasis (P<0.050). The positive rate of AR protein expression was not correlated with the age, menstrual status, tumor diameter, progesterone receptor and Her-2 statuses, Ki-67, or molecular typing (P>0.050). The 3-year and 5-year overall survival and tumor-free survival of the AR-positive patients were significantly higher than those of the AR-negative patients (P<0.050). The 5-year cumulative total survival and tumor-free survival of the AR-positive patients were significantly better than those of the AR-negative patients (χ2=8.134, P=0.004; χ2=9.150, P=0.002).ConclusionsPatient with AR protein positive expression in ER-positive breast cancer has a better differentiation, lower clinical stage, and weaker invasiveness. Long-term survival of patient with AR protein positive expression after standardized treatment is also better than that of patient with AR protein negative expression. It might provide an important additional information on prognosis and become a promising object for targeted therapy.
ObjectiveTo study the correlation of lymph node metastasis and recurrence with body mass index (BMI) and estrogen receptor (ER) in papillary thyroid carcinoma (PTC).MethodThe relevant literatures were retrieved in the past six years through the CNKI, VIP, Wanfang, CBM, PubMed, Medline, Embase, Cochrane Library, etc. databases for meta-analysis of relationship of lymph node metastasis and recurrence of PTC with BMI or ER and its subtypes.ResultsThe meta-analysis showed that the lymph node metastasis of PTC was associated with the BMI and ERα [OR=1.27, 95% CI (1.12, 1.42), P<0.000 1; OR=2.68, 95% CI (1.86, 3.86), P<0.000 01, respectively ], and which not associated with the ER and ERβ [OR=0.87, 95% CI (0.56, 1.35), P=0.53; OR=1.22, 95% CI (0.78,1.89), P=0.39, respectively ]. The ERα was associated with the PTC recurrence [OR=1.87, 95% CI (1.04, 3.35), P=0.04 ], but the BMI was not the risk factor for the recurrence of PTC [OR=1.187 1, 95% CI (0.930 0, 1.515 3), P=0.17 ].ConclusionsAlthough BMI was not found to be associated with PTC recurrence, high BMI promotes PTC metastasis, so lymph node dissection in obese patients should be more careful and comprehensive. Positive ERα increases risk of lymph node metastasis and recurrence of PTC, which can be used as a negative factor in evaluating prognosis of PTC and provide a new idea for endocrine therapy of PTC.
ObjectiveTo investigate the effect of circulating estrogen level on the outcome of free fat grafting in nude mice.MethodsEighteen female nude mice aged 6-8 weeks (weighing, 20-25 g) were randomly divided into 3 groups (n=6). The nude mice in the ovariectomized group were treated with ovariectomy. The nude mice in the high estrogen group and the normal estrogen group only made the same incision to enter the peritoneum without ovariectomy. The nude mice in the high estrogen group were given the estradiol (0.2 mg/g) every 3 days for 30 days. The other two groups were given the same amount of PBS every 3 days. At 30 days after operation, the tail vein blood of nude mice in 3 groups were detected by estradiol ELISA kit, and the free fat (0.3 mL) donated by the females was injected into the sub-scalp of nude mice. After 8 weeks of fat grafting, the samples were taken for gross observation and weighing, and the prepared slices were stained with HE staining, CD31-perilipin fluorescence staining, immunohistochemical staining of uncoupling protein 1 (UCP1), and immunofluorescence staining of estrogen receptor α. The diameter of adipocytes and vascular density of adipose tissue were measured. The mRNA expressions of UCP1 and estrogen receptor α were detected by realtime fluorescence quantitative PCR (qRT-PCR).ResultsAll nude mice survived during experiment. ELISA test showed that the concentration of estradiol significantly decreased in the ovariectomized group and increased in the high estrogen group compared with the normal estrogen group (P<0.05). At 8 weeks after fat grafting, the graft volume from large to small was ovariectomized group, normal estrogen group, and high estrogen group. There was significant difference in wet weight between the ovariectomized group and high estrogen group (P<0.05). Section staining showed that compared with the normal estrogen group, the adipocytes in the ovariectomized group were larger, the expression of peri-lipoprotein was weaker, the vascular density decreased, and the expressions of UCP1 was negative, and the estrogen receptor α positive cells reduced. The above observation results in the high estrogen group were contrary to those in the ovariectomized group. There were significant differences in the diameter of adipocytes, the vascular density of adipose tissue, the number of the estrogen receptor α positive cells between groups (P<0.05). The results of qRT-PCR showed that the mRNA expressions of UCP1 and estrogen receptor α significantly increased in the high estrogen group and decreased in the ovariectomized group compared with the normal estrogen group, and the differences were significant (P<0.05).ConclusionThe level of circulating estrogen has a significant effect on the outcome of free fat grafting in nude mice. Low estrogen level leads to hypertrophy of graft adipocytes, while high estrogen level leads to the production of a large amount of beige fat and high vascular density in fat grafts, which may be related to the activation of estrogen receptor α on adipocytes.
The purpose of this study was to investigate the effect of low-magnitude vibration on osteogenesis of osteoblasts in ovariectomized rats with osteoporosis via estrogen receptor α(ERα). The mRNA expression of osteogenic markers were examined with qRT-PCR, based on which the optimal vibration parameter for promoting osteogenesis was determined (45 Hz × 0.9 g, g = 9.8 m/s2). Then we loaded the optimal vibration parameter on the osteoblasts of ovariectomized rats with osteoporosis. The protein expression of osteogenic markers and ERα were detected with Western blot; the distribution of ERα was examined with immunofluorescence technique. Finally, through inhibiting the expression of ERα with estrogen receptor inhibitor ICI182780, the protein and mRNA expression of osteogenic markers were examined. First, the results showed that low-magnitude vibration could promote the expression of osteogenic markers and ERα in osteoblasts of ovariectomized rats with osteoporosis (P < 0.05), and make ERα transfer to the nucleus. On the other hand, the results also showed that after inhibiting the expression of ERα in osteoblasts of ovariectomized rats with osteoporosis, the protein and mRNA expression of osteogenic marker were decreased (P < 0.05). In our study, low-magnitude vibration played an important role in the osteogenesis of osteoblasts in ovariectomized rats with osteoporosis through increasing the expression and causing translocation of ERα. Furthermore, it provides a theoretical basis for the application of low-magnitude vibration in the prevention and treatment of postmenopausal osteoporosis.
ObjectiveTo investigate whether Osteoglycin (OGN) gene inhibits the proliferation of Luminal breast cancer cells by up-regulating the expression of estrogen receptor (ER). Methods① Ualcan online database was used to analyze the expression of OGN in the breast cancer, and Kaplan-Meier Plotter was used to analyze the effect of OGN on the prognosis of patients with breast cancer. The median OGN mRNA expression level was taken as the cut-off point for high or low OGN expression. ② The expression of OGN mRNA in the Luminal breast cancer tissue of clinical case was examined using real time quantitative PCR (qRT-PCR). ③ Up-regulation of OGN expression in the Luminal breast cancer cell lines MCF-7 and T47D cells by transfection of overexpressing OGN plasmid, the expressions of OGN and ER were detected by qRT-PCR and Western blot, respectively. CCK8 assay and colony formation assay were applied to detect the cell proliferation and colony formation of Luminal breast cancer cells. ④ siRNA transfection was used to interfere with the expression of ER (ESR1) of breast cancer cells in the overexpressing OGN of breast cancer cells, then the CCK8 assay was used to detect the proliferation ability of the breast cancer cell lines after down-regulating the expression of ER in the overexpressing OGN patients. Results① The results of Ualcan online database showed that the expression of OGN mRNA in the breast cancer tissues of different types of breast cancer was lower than that in the normal breast tissues (P<0.001), and which was highest in the Luminal breast cancer tissues (P<0.001). The Kaplan-Meier Plotter prognosis analysis showed that in all breast cancer or Luminal breast cancer patients, the prognosis of patients with high OGN expression was better than those with low OGN expression (P=0.000 14, P=0.001 80). ② The OGN mRNA expression was decreased in the 30 Luminal breast cancer samples as compared with the corresponding adjacent normal breast tissues (t=4.774, P=0.000 019). ③ The expressions of OGN and ER in the MCF-7 and T47D cells were up-regulated after transfection of overexpressing OGN plasmid (P=0.000 002, P=0.000 001). The cell proliferation was inhibited (P<0.05) and the number of cell clones was decreased significantly (P<0.05). ④ After transient transfection of siRNA interfered with breast cancer cell lines of overexpressing OGN, ER mRNA level decreased (P<0.05), and cell proliferation ability increased significantly (P<0.05). Conclusion OGN could exert a tumor suppressor effect in Luminal breast cancer by mediating expression of ER.
ObjectiveTo analyze the clinicopathologic characteristics and prognosis of human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients with different expression status of estrogen receptor (ER). MethodsThe patients with HER2-negative breast cancer met the inclusion and exclusion criteria and were treated in the Affiliated Hospital of Southwest Medical University from January 1, 2017 to December 31, 2019 were retrospectively collected, and then were assigned into 3 groups according to the ER expression status: ER-negative (ER expression positive rate <1%) group, ER-low expression (ER expression positive rate 1%–10%) group, and ER expression positive rate >10% group. The differences of clinicopathologic characteristics, therapy, and prognosis among the 3 groups were compared. And the risk factors affecting recurrence and metastasis of patients with ER-low expression were analyzed by Cox proportional hazards regression model. ResultsA total of 610 patients with HER2-negative breast cancer were included in this study, including 130 patients in the ER-negative group, 48 patients in the ER-low expression group, and 432 patients in the ER expression positive rate >10% group. The Bonferroni method was used to correct the test level after pairwise comparison, it was found that the histological grade was later (P<0.001, P=0.023) and the Ki-67 expression was higher (P<0.001, P=0.023) in the ER-negative group and ER-low expression group as compared with the ER expression positive rate >10% group; The proportion of the patients receiving chemotherapy in the ER-negative group was higher than that of the ER expression positive rate >10% group (χ2=10.310, P=0.001), while which had no statistical difference between the ER-low expression group and the ER-negative group or the ER expression positive rate >10% group (Fisher exact probability method, P=1.000; χ2= 3.585, P=0.058); The proportion of patients receiving endocrine therapy in the ER-low expression group was higher than that in the ER-negative group (χ2=36.333, P<0.001) and lower than the ER expression positive rate >10% group (χ2=246.996, P<0.001). The difference in disease-free survival (DFS) curves among 3 groups was statistically significant (χ2=46.805, P<0.001); There were no statistical differences in the overall survival (OS) curve and DFS curve between the ER-negative group and the ER-low expression group (Two stage test, P=0.786; χ2=1.141, P=0.286), and which in the ER expression positive rate >10% group were significantly better than thoses in the ER-negative group (χ2=10.137, P=0.001; χ2=39.344, P<0.001) and the ER-low expression group (χ2=4.075, P=0.044; χ2=31.911, P<0.001). The results of multivariate Cox proportional hazards regression analysis showed that N1 and N2 [N0 as reference: RR (95%CI)=7.740 (1.939, 30.897), P=0.004; RR (95%CI)=9.513 (1.990, 45.478), P=0.005) and T3 [T1 as reference: RR (95%CI)=27.357 (2.188, 342.041), P=0.010] increased the probabilities of recurrence and metastasis HER2-negative breast cancer patients with ER-low expression. ConclusionsAccording to results of this study, patients with HER2-negative breast cancer showed certain differences in histological grade and Ki-67 expression among patients with three different ER expression status, but no statistical difference is found between ER-low expression and ER-negative breast cancer, and the prognoses of both are worse than that of ER expression positive rate >10% breast cancer patients. Lymph node metastasis and larger tumor are risk factors affecting recurrence and metastasis in ER-low expression breast cancer patients.