Vaginal metastasis from breast cancer: A case report.

Breast cancer is one of the most common malignancies in women. However, cases of vaginal metastases of breast cancer are rarely reported in China and abroad. The main clinical symptom of vaginal metastases of breast cancer is vaginal bleeding. This article aims to provide a reference for the diagnosis and clinical management of vaginal metastases from breast cancer. This article describes in detail the management of a 50-year-old woman with vaginal metastases from breast cancer, who was admitted to the hospital with persistent vaginal bleeding without apparent causes. Persistent vaginal bleeding was found after two and a half years when her breast cancer surgery was performed. After comprehensive evaluation, vaginal mass resection was performed. Postoperative histopathology confirmed that the vaginal mass was breast cancer metastasis. The patient was treated with local radiotherapy and three cycles of eribulin and bevacizumab after the vaginal mass was removed. A reexamination of computed tomography showed that the chest wall metastases were less extensive than before. Orbital metastases were also reduced in size, which was revealed by the physical examination. The patient had since failed to return to hospital on time for a regular treatment due to personal reasons. After 9 months of follow-up, the patient died of multiple metastases. The diagnosis of vaginal masses is based on pathological examination, and systemic treatment should be the mainstay when extensive metastases are presented.

Has_circ_0048764 promotes breast cancer progression by sponging miR-578 and regulating HMGA2 expression.

BACKGROUND: Circular RNAs (circRNAs) function as important regulators in the progression of cancers. The role of circRNA_0048764 (circ_0048764) in the development of breast cancer (BC) remains inconclusive. This work investigates the biological function and molecular mechanism of circ_0048764 in BC. METHODS: Quantitative real-time PCR (qRT-PCR) was conducted to measure the expression levels of circ_0048764, microRNA-578 (miR-578) and high mobility group AT-hook 2 (HMGA2) mRNA. The viability of BC cells was examined by cell counting kit 8 (CCK-8) assay. Besides, cyclin D1, proliferating cell nuclear antigen (PCNA) and HMGA2 expression levels were detected by western blot. The migrative and invasive capability of BC cells were probed by transwell assay. The relationships between miR-578 and circ_0048764 or HMGA2 3'-UTR were validated by dual-luciferase reporter gene assay. RESULTS: Circ_0048764 was highly expressed in BC tissues and cells, which was significantly associated with tumor size (≥2 cm), lymph node status (positive), and higher TNM stage of BC patients. Circ_0048764 depletion suppressed the proliferative, migrative, and invasive abilities of BC cells, which was rescued by transfection of miR-578 inhibitors. The binding sites were verified between circ_0048764 and miR-578. HMGA2 was identified to be a target of miR-578 in BC cells, and circ_0048764 positively regulated HMGA2 expression in BC cells via repressing miR-578. CONCLUSION: Circ_0048764 promotes BC cell growth, migration and invasion via absorbing miR-578 and up-regulating HMGA2.

The prognostic role of lymph node ratio in breast cancer patients received neoadjuvant chemotherapy: A dose-response meta-analysis.

Background: As neoadjuvant chemotherapy is widely used in breast cancer patients, the lymph node ratio has not been fully validated as a prognostic indicator of breast cancer received neoadjuvant chemotherapy. This study was conducted to investigate the prognostic value of lymph node ratio in breast cancer patients received neoadjuvant chemotherapy. Methods: Systematic searches were performed in the PubMed, Embase, and Cochrane Library databases until 15 December 2021 for studies on the association between lymph node ratio and the prognosis of breast cancer after neoadjuvant chemotherapy. Overall survival and disease-free survival were used as outcome events, and hazard ratio was chosen as the parameter to evaluate the correlation. The dose-response relationship was assessed by restricted cubic splines. In the subgroup analyses, which were used to explore potential heterogeneity among the included studies according to study region and sample size. Sensitivity analysis was performed to assess the stability of individual studies, and publication bias was determined with funnel plots, Begg's test, and Egger's test. All statistical analyses were performed using Stata 15.1. Results: A total of 12 studies with 4,864 patients were included in this meta-analysis. In this study, high lymph node ratio was significantly associated with decreased overall survival (HR: 4.74; 95%CI: 3.36-6.67; P < 0.001) and disease-free survival (HR: 4.77; 95%CI: 3.69-6.17; P < 0.001). Moreover, the dose-response meta-analysis showed a linear association between higher lymph node ratio and shorter overall survival and disease-free survival in breast cancer patients after neoadjuvant chemotherapy. Conclusions: The meta-analysis suggested that high lymph node ratio was significantly associated with short overall survival and disease-free survival in breast cancer patients after neoadjuvant chemotherapy. Therefore, lymph node ratio is an independent predictive factor for the prognosis of breast cancer patients after neoadjuvant chemotherapy, which may better refine the cancer staging system.

Artificial Intelligence-Based Breast Cancer Diagnosis Using Ultrasound Images and Grid-Based Deep Feature Generator.

Purpose: Breast cancer is a prominent cancer type with high mortality. Early detection of breast cancer could serve to improve clinical outcomes. Ultrasonography is a digital imaging technique used to differentiate benign and malignant tumors. Several artificial intelligence techniques have been suggested in the literature for breast cancer detection using breast ultrasonography (BUS). Nowadays, particularly deep learning methods have been applied to biomedical images to achieve high classification performances. Patients and Methods: This work presents a new deep feature generation technique for breast cancer detection using BUS images. The widely known 16 pre-trained CNN models have been used in this framework as feature generators. In the feature generation phase, the used input image is divided into rows and columns, and these deep feature generators (pre-trained models) have applied to each row and column. Therefore, this method is called a grid-based deep feature generator. The proposed grid-based deep feature generator can calculate the error value of each deep feature generator, and then it selects the best three feature vectors as a final feature vector. In the feature selection phase, iterative neighborhood component analysis (INCA) chooses 980 features as an optimal number of features. Finally, these features are classified by using a deep neural network (DNN). Results: The developed grid-based deep feature generation-based image classification model reached 97.18% classification accuracy on the ultrasonic images for three classes, namely malignant, benign, and normal. Conclusion: The findings obviously denoted that the proposed grid deep feature generator and INCA-based feature selection model successfully classified breast ultrasonic images.

MicroRNA-124-3p.1 promotes cell proliferation through Axin1-dependent Wnt signaling pathway and predicts a poor prognosis of triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is one subtype of breast cancer, which is characterized by an aggressive disease. It is commonly accompanied with extremely poor prognosis because of no available molecularly targeted therapy. Thus, understanding the detailed molecular mechanisms of TNBC is urgently needed. METHODS: The levels of Axis inhibition protein 1 (Axin1), Cyclin D1, c-Myc, and miR-124-3p.1 were measured by quantitative real-time PCR (qRT-PCR). Furthermore, the breast cancer cell proliferation was measured by CCK-8 assay, colony formation assays, and EdU staining. Xenograft model was used to show the tumor genesis of breast cancer cells. The regulatory function of miR-124-3p.1 on Wnt/ß-catenin signaling activation through directly targeting Axin1 was proven using qRT-PCR, Western blot analysis, and dual-luciferase reporter assay. To further assess the clinical significance of miR-124-3p.1 in the prognosis of breast cancer patients, we performed Kaplan-Meier survival analysis and log-rank tests. RESULTS: miR-124-3p.1 expression was elevated in advanced TNBC patients, and high miR-124-3p.1 predicts poor overall survival in TNBC patients. Further data showed that miR-124-3p.1 downregulation diminished, while miR-124-3p.1 upregulation increased the growth of TNBC cells in vitro and in vivo. Finally, we proved that miR-124-3p.1 exerted its function via targeting tumor suppressor gene Axin1 and activating the Wnt signaling pathway. CONCLUSION: In summary, all the results demonstrate that miR-124-3p.1 promotes TNBC cell growth by controlling Axin1, suggesting that targeting miR-124-3p.1 might offer an effective therapeutic strategy for TNBC in the future.

Upregulation Of miR-153 Inhibits Triple-Negative Breast Cancer Progression By Targeting ZEB2-Mediated EMT And Contributes To Better Prognosis.

BACKGROUND: Triple-negative breast cancer (TNBC) is the most malignant type of breast cancer. MicroRNAs (miRs) and their corresponding molecular targets are associated with the occurrence and development of various human malignancies. However, the roles of the microRNA-153 (miR-153) and zinc finger E-box-binding homeobox 2 (ZEB2)-induced epithelial-mesenchymal transition (EMT) in TNBC and predictive effect of miR-153 on the prognosis of TNBC have not been fully elucidated. MATERIALS AND METHODS: Relative miR-153 expression level was examined by RT-qPCR assay in TNBC tissues of 60 patients and TNBC cell lines (SKBR3, BT-549 and MDA-MB-231). Cell proliferation ability, invasion ability and migration ability were measured by CCK8 assay, Transwell invasion assay and wound healing assay, respectively. Luciferase reporting experiment was used to confirm that there was a miR-153-binding site in ZEB2 3'-UTR. The expression of ZEB2 in tissues and its relationship with miR-153 were analyzed with immunohistochemistry method. Relative ZEB2, E-cadherin, N-cadherin and Vimentin mRNA and protein expression levels were observed with RT-qPCR and Western blot, respectively. Based on risk factors, a prognostic model was established according to the Cox proportional risk model, and the prognostic risk factors of TNBC patients were predicted and analyzed. RESULTS: The expression of miR-153 in TNBC tissues and cells was declined (all P<0.01), and upregulation of miR-153 inhibited proliferation, invasion and migration of TNBC cells (all P<0.01). In addition, miR-153 regulated ZEB2/EMT link in TNBC, and ZEB2 overexpression reversed the tumor-suppressive effect of miR-153 in TNBC. Moreover, miR-153 was an independent predictive factor that was associated with excellent prognosis in TNBC patients. CONCLUSION: miR-153 may inhibit TNBC proliferation, invasion and migration by regulating ZEB2/EMT link. Therefore, miR-153 is expected to be a molecular target and prognostic marker for TNBC.

Heterogeneous nuclear ribonucleoprotein M promotes the progression of breast cancer by regulating the axin/ß-catenin signaling pathway.

Despite significant progress in the treatment of breast cancer due to advances in surgery, cytotoxic agents, and endocrine therapy, the prognosis for patients has not improved much. Accumulated evidence indicates that heterogeneous nuclear ribonucleoprotein M (hnRNPM) and Wnt/ß-catenin function as tumor oncogenes in the progression of many cancers. The present study aimed to explore whether HnRNPM/ß-catenin signaling molecules might serve as a genetic target for breast cancer treatment. To shed light on this issue, quantitative real-time polymerase chain reaction (qRT-PCR) detection, Western blotting, and immunohistochemical staining were performed. The hnRNPM is expressed at a much higher level in breast cancer tissues and cell lines than in noncancerous tissues and cell lines. In vitro studies revealed that overexpressed hnRNPM promoted cell proliferation and colony formation but inhibited cell apoptosis. In vivo results demonstrated that upregulation of hnRNPM dramatically increased breast cancer xenograft tumor growth. Western blotting and immunofluorescence studies revealed that hnRNPM markedly activated the Wnt/ß-catenin pathway and catalyzed its translocation from the cytoplasm to the nucleus by targeting axin, a negative regulator of Wnt/ß-catenin signaling in MCF-7 and KPL-4 cells. Elevated levels of c-Myc and cyclin D1 were observed when MCF-7 and KPL-4 cells were transfected with a hnRNPM vector. These findings indicate that the hnRNPM/axin/ß-catenin signaling pathway acts as an oncogenic promoter in the progression of breast cancer, suggesting that hnRNPM may be a potential target for the treatment of this disease.

Higher expression level of tyrosine kinase-like orphan receptor 2 and Wnt member 5a in papillary thyroid carcinoma is associated with poor prognosis.

The tyrosine kinase-like orphan receptor 2 (ROR2) has a wnt-mediated, pro-tumorigenic role in certain types of cancer. The present study was designed to assess the protein expression level of ROR2 and its putative ligand Wnt member 5a (Wnt5a), as well as the association with clinicopathological features in papillary thyroid carcinoma (PTC). A total of 58 patients were recruited, resulting in 58 human PTC tissue samples and their paired adjacent noncancerous tissue samples being obtained. The protein expression levels of ROR2 and Wnt5a were evaluated by immunohistochemistry and western blotting, and messenger RNA expression levels were determined by reverse transcription-quantitative polymerase chain reaction. ROR2 and Wnt5a protein and mRNA expression were significantly overexpressed in PTC tissues (P<0.05). The present study also revealed that ROR2 and Wnt5a were significantly associated with tumor stage and lymph node metastasis (P<0.05). There was a positive association between ROR2 and Wnt5a expression levels (r=0.857; P=0.007). In conclusion, ROR2 and Wnt5a may act as tumor suppressor genes in the development of PTC; overexpression of ROR2 and Wnt5a in PTC may be important for tumorigenesis and tumor development.

Association between transforming growth factor-ß1 expression and the clinical features of triple negative breast cancer.

The aim of the present study was to investigate the association between the expression levels of transforming growth factor-ß1 (TGF-ß1) and the clinical pathological characteristics and prognosis of triple negative breast cancer (TNBC) through study of TNBC patient tissue samples. The biological effects of TGF-ß1 on TNBC cells and the potential signal transduction pathway are additoinally investigated. Immunohistochemistry was utilized to investigate expression changes of the positive rate of TGF-ß1 in the TNBC, compared with the non-TNBC group, to explain the association between TGF-ß1 and clinical pathological characteristics and prognosis. MDA-MB-231 cells were treated with TGF-ß1 and subsequently the invasion and migration abilities, and the expression of proteins in certain signaling pathways were assessed before and after the treatment. Positive expression of TGF-ß1 was observed in 52.5% of TNBC tissue samples, which was higher than that observed in non-TNBC group (27.5%). High levels of TGF-ß1 expression were not significantly associated age, menopausal status, family history of cancer or tumor size; however, tumor histological grade and axillary lymph node metastasis were significantly associated (P<0.05). In addition, when the TGF-ß1 expression levels are higher, the 5-year disease-free survival rate is lower. TGF-ß1 expression promoted the invasion and migration of MDA-MB-231 cells, and the expression of Smad2 protein and P38 protein was increased, indicating that Smad2 protein and the P38 signaling pathway may serve an important role in TNBC.

miR-935 promotes gastric cancer cell proliferation by targeting SOX7.

Gastric cancer is the most common cancer in the world, miRNAs have been demonstrated to play critical role in the development and progression of gastric cancer, such as miR-7, miR-217 and miR-335. Here, we found miR-935 was upregulated in gastric cancer tissues and cells. Overexpression of miR-935 promoted cell proliferation and tumorigenesis in vitro determined by MTT analysis, colony formation analysis, BrdU cell proliferation analysis and soft agar growth analysis, knockdown of miR-935 reduced these effects. Tumor suppressor sex-determining region Y-box 7 (SOX7) was the direct target of miR-935, overexpression of miR-935 inhibited SOX7 expression, but promoted the levels CCND1 and C-MYC which promotes cell proliferation and tumorigenesis, knockdown of miR-935 increased SOX7 level, and inhibited CCND1 and C-MYC expression. Synchronous knockdown of miR-935 and SOX7 promoted cell proliferation and tumorigenesis in vitro, confirming miR-935 regulated gastric cancer cell proliferation by inhibiting SOX7. In summary, we found miR-935 contributed to cell proliferation of gastric cancer through targeting SOX7.

[Correlation between characteristics of lymph node metastases and prognosis in pancreatic cancer treated with pancreaticoduodenectomy].

OBJECTIVE: To study the correlation between characteristics of lymph node metastases and prognosis in pancreatic cancer treated with pancreaticoduodenectomy. METHODS: The clinicopathological data of consecutive series of 122 patients who underwent resection for adenocarcinoma of the pancreas with lymphadenectomy in our hospital were reviewed in this study. The number of metastatic lymph nodes, lymph node metastasis ratio, lymph node levels, and other clinocopathological factors were analyzed by Kaplan-Meier method and Cox proportional hazard model, and their correlation with prognosis was also analyzed. RESULTS: 122 patients met the inclusion criteria and entered the study. There were 90 patients (73.8%) with lymph node metastases. Median (range) metastatic lymph node number was 7 (1-28) for the entire cohort, and median (range) metastatic lymph node ratio was 21.1% (3.6%-62.2%). The numbers of patients with lymph nodes metastases to levels 1, 2, 3 were 39 (43.3%), 40 (44.4%), and 11 (12.2%), respectively. Univariate analysis suggested that the maximum diameter of tumor, lymph node metastases, number, ratio, level, distant metastases and adjuvant chemotherapy were significantly related to survival in the entire cohort (P < 0.05). The maximum diameter of tumor, lymph node metastasis number, ratio, level, and adjuvant chemotherapy were significantly related to the survival in node-positive patients (P < 0.05). Multivariate analysis suggested that the diameter of tumor >2 cm, lymph node metastases, metastatic lymph node number >2, ratio >20%, level >1, and without adjuvant chemotherapy were independent risk factors of survival in the entire cohort (P < 0.05). The maximum diameter of tumor >2 cm, metastatic lymph node number >2, ratio >20%, level >1 and without adjuvant chemotherapy were independent risk factors of survival in node-positive patients (P < 0.05 for all). CONCLUSIONS: The three indexes, metastatic number, ratio and extent of lymph nodal involvement are statistically significant prognostic factors in pancreatic cancer, which can complement the existing lymph node metastasis staging. The standardized pancreaticoduodenectomy combined with proper lymphodenectomy provides an important basis for a correct prognostic evaluation.