Genetic evidence supporting potential causal roles of EIF4 family in breast cancer: a two-sample randomized Mendelian study.

Translational control plays a crucial role in the regulation of apoptosis, with the EIF4 family serving as one of the mRNA translation factors that modulate the process of mRNA translation based on mRNA characteristics. To address this potential causal role of EIF4 family proteins and breast cancer, Mendelian randomization was employed. The study incorporated four sets of genetics instrumental variables, namely EIF4E, EIF4B, EIF4A, and EIF4EBP2. The outcome variables selected for analysis were the BCAC consortium, which included estrogen receptor positive (ER+) and estrogen receptor negative (ER-) samples. To assess the potential violations of the MR assumption, the primary MR analysis employed inverse variance weighted (IVW), and several sensitivity analyses were conducted. The findings of the two-sample MR analysis indicate that EIF4E has an adverse effect on breast cancer risk (p = 0.028). However, the evidence for the relationship between EIF4E and ER status of breast cancer suggests a weak association with ER+ breast cancer (p = 0.054), but not with ER- breast cancer (p > 0.05). The study findings indicate that EIF4A is not causally linked to the risk of ER+ breast cancer, but is significantly associated with an elevated risk of ER- breast cancer (p = 0.028). However, the evidence is inadequate to support the effects of EIF4B and EIF4EBP2 on breast cancer (p > 0.05). Our results suggest that EIF4 may be a potential factor in the occurrence and development of breast cancer, which may lead to a better understanding of its causes and prevention.

High GPER expression in triple-negative breast cancer is linked to pro-metastatic pathways and predicts poor patient outcomes.

Triple-negative breast cancer (TNBC) is a particularly aggressive and heterogeneous disease with few effective targeted therapies and precision therapeutic options over a long period. It is generally considered that TNBC is an estrogen-independent breast cancer, while a new estrogen receptor, namely G protein-coupled estrogen receptor (GPER), is demonstrated to mediate estrogenic actions in TNBC. Based on our transcriptomic analysis, expression of GPER was correlated with clinicopathological variables and survival of 360 TNBC patients. GPER expression at mRNA level was significantly correlated with immunohistochemistry scoring in 12 randomly chosen samples. According to the cutoff value, 26.4% (95/360) of patients showed high GPER expression and significant correlation with the mRNA subtype of TNBC (P = 0.001), total metastatic events (P = 0.019) and liver metastasis (P = 0.011). In quantitative comparison, GPER abundance is correlated with the high-risk subtype of TNBC. At a median follow-up interval of 67.1 months, a significant trend towards reduced distant metastasis-free survival (DMFS) (P = 0.014) was found by Kaplan-Meier analysis in patients with high GPER expression. Furthermore, univariate analysis confirmed that GPER was a significant prognostic factor for DMFS in TNBC patients. Besides, high GPER expression was significantly linked to the worse survival in patients with lymph node metastasis, TNM stage III as well as nuclear grade G3 tumors. Transcriptome-based bioinformatics analysis revealed that GPER was linked to pro-metastatic pathways in our cohort. These results may supply new insights into GPER-mediated estrogen carcinogenesis in TNBC, thus providing a potential strategy for endocrine therapy of TNBC.

RETRACTED: Loss of microRNA-30e induced by extracellular vesicles from cancer-associated fibroblasts promotes breast cancer progression by binding to CTHRC1.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the authors as "some data in this study are not solid enough and need to be further explored". The authors stated that they "found abnormalities in the re-identification of CAF-EVs, the extracted extracellular vesicles may be polluted and the elliptical structure under electron microscope is not owned by CAF-EVs. The identification of CAF-EVs by Western Blots did not refer to the definition of international society." The authors informed the journal that, after the re-experiment, they found that "there is no vesicle specific protein expression, whether the results of subsequent experiments are generated by CAF-EVs needs to be re-tested".

Idiopathic Granulomatous Mastitis with Skin Rupture: A Retrospective Cohort Study of 200 Patients Who Underwent Surgical and Nonsurgical Treatment.

BACKGROUND: Idiopathic granulomatous mastitis (IGM) can clinically and radiographically mimic an abscess or breast cancer. Although IGM is benign, it can cause the breast skin to appear "riddled with holes" and can even result in the loss of the breast. The optimal treatment has not been established. METHODS: We retrospectively studied the medical records of 200 patients with IGM who were treated for skin rupture from June 2015 to June 2017 in our institute. The patients' treatment modalities (including surgery after steroid therapy and steroid therapy alone), outcomes, and scores of satisfaction questionnaires were analyzed. The time to healing and recurrence rate were compared with a focus on the treatment modalities to identify the most effective treatments for IGM. RESULTS: The median follow-up time was 15.64 months (range, 12-36 months). In total, 156 patients were treated with surgery after steroid therapy and 44 were treated with steroid therapy alone. The median times to healing in the surgical and nonsurgical groups were 25 and 258 days, respectively (p = 0.003). Four of 156 (2.56%) patients developed post-excision wound complications. Eight of 156 patients (5.1%) in the surgical group and 10 of 44 (22.7%) patients in the nonsurgical group developed recurrence (p < 0.01). The scores of the satisfaction questionnaire were 36 ± 4.28 in the surgical group and 24 ± 8.62 in the nonsurgical group (p = 0.017). CONCLUSION: IGM is a benign disease but can have serious consequences. Surgery after steroid therapy is an effective and more satisfactory treatment than steroid therapy alone.

BRCA2 c.8827C>T pathogenic mutation in a consanguineous Chinese family with hereditary breast cancer.

BACKGROUND: Mutations in the BRCA2 DNA repair associated gene (BRCA2) are associated with the development of breast cancer, with different ethnic mutations at different sites. Based on different types of BRCA2 variants, the underlying mechanism remains still elusive. METHODS: Next-generation sequencing (NGS) was performed to detect germ line mutations in BRCA2. The expressions of BRCA2 mRNA and BRCA2 protein were detected by Real-time PCR and Western blot, respectively. RESULTS: In a consanguineous Chinese family with hereditary breast cancer, one woman had unilateral breast cancer, two women had bilateral asynchronous breast cancer, and one man had prostate cancer. We identified a mutation site (NM_000059.4: c.8827C>T, NP_ 000050.3: p.(Gln2943*)) in BRCA2 gene, which was a nonsense mutation that predicted disrupting peptide chain synthesis and limiting BRCA2 protein production, validated by the decreased expressions of both BRCA2 mRNA and BRCA2 protein. CONCLUSION: In this study, we identified a BRCA2 c.8827C>T nonsense mutation with a truncated BRCA2 protein in a consanguineous Chinese Han family, suggesting individuals with this mutation should be regularly screened for malignancies such as breast, prostate, and ovarian cancer. Our study verified the function of this BRCA2 mutation site and provided a new target for the precise treatment of such patients.

LncRNA WT1-AS Inhibits Triple-Negative Breast Cancer Cell Migration and Invasion by Downregulating Transforming Growth Factor ß1.

Background: Long noncoding RNA WT1-AS has been demonstrated as a potential tumor suppressor in gastric cancer. However, the functions of WT1-AS in other types of cancer remain unclear. Our study was therefore performed to explore the role of WT1-AS in triple-negative breast cancer (TNBC). Materials and Methods: Tissue specimens were obtained from 62 TNBC patients included in this study. A TNBC cell line BT-549 was used as the cell model of TNBC. Gene expression was detected by qPCR and Western blot. Overexpression experiments were used to analyze gene interactions. Transwell assays were used to explore the effects of transfections on cell invasion and migration. Results: We found that WT1-AS was downregulated in TNBC tissues than in nontumor tissues and decreased with increase in clinical stages. Transforming growth factor ß1 (TGF-ß1) was upregulated in TNBC tissues and inversely correlated with WT1-AS. TGF-ß1 overexpression did not significantly affect WT1-AS in BT-549 cells, but WT1-AS negatively regulated the expression of TGF-ß1. WT1-AS overexpression caused inhibited migration and invasion of TNBC cells. TGF-ß1 overexpression showed opposite functions and reduced the effects of WT1-AS overexpression. Conclusion: WT1-AS may downregulate TGF-ß to inhibit the migration and invasion of TNBC cells.

[Differential expression of miR-21, miR-126, miR-143, miR-373 in normal cervical tissue, cervical cancer tissue and Hela cell].

OBJECTIVE: To investigate the differential expression of miR-21, miR-126, miR-143 and miR-373 in normal cervical tissue, cervical cancer tissue and Hela cell. METHODS: The expressions of miR-21, miR-126, miR-143 and miR-373 were detected by real-time PCR in cervical cancer tissue, cervical tissue of benign uterine tumor and Hela cell. RESULTS: High expression of miR-21 was observed in cervical cancer and Hela cell, while low expression was observed in normal cervical tissue. The relative quantification of miR-21 in cerveical cancer was 11.3196 times that of miR-21 in normal cervical tissue (P < 0.05). The expression levels of miR-143 and miR-373 in cervical cancer and Hela cell were lower than those of normal cervical tissue. The relative quantification of miR-143 in cerveical cancer was 0.1553 times that of normal cervical tissue (P < 0.05), and the relative quantification of miR-373 in cerveical cancer was 0.4907 times that of normal cervical tissue (P < 0.05). The expression of miR-126 had no significant difference among cervical cancer tissue, Hela cell and normal cervical tissue (P > 0.05). CONCLUSION: miRNAs are closely related to the occurrence and regulation of cervical cancer. The high expression of miR-21 in cervical cancer and Hela cell indicate that it may play a possible role of oncogenes, while miR-143 and miR-373 with low expression may play the role of tumor suppressor genes.