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Purpose: Our aim was to verify whether KIF20A has the potential to serve as a prognostic marker for female patients with estrogen receptor (ER)-positive breast cancer (BC) and treated with tamoxifen (TAM). Patients and Methods: Online tools were used to investigate the potential correlation between KIF20A gene expression and survival of patients with ER-positive BC and TAM treatment. Furthermore, immunohistochemistry (IHC) was conducted to assess the expression levels of KIF20A in patients included from our center. The prognostic value of KIF20A for disease-free survival (DFS) and overall survival (OS) was further evaluated using Cox regression analysis. Results: According to the results obtained from online tools, it was found that patients with low KIF20A expression exhibited significantly better survival outcomes in terms of relapse-free survival (RFS), distant metastasis-free survival (DMFS), and OS compared to those with high KIF20A expression (P < 0.001, P < 0.001, and P = 0.008, respectively). Additionally, significantly lower gene expression of KIF20A was found in patients who responded to TAM than in those who did not respond to TAM (P < 0.001). We further included 203 patients with adjuvant TAM therapy, and IHC for KIF20A was performed on sections from paraffin-embedded blocks. Patients with low KIF20A expression had significantly better DFS and OS (P = 0.001 and 0.002, respectively, log rank test), and the expression of KIF20A was identified as an independent factor for predicting both DFS and OS (P = 0.001 and 0.008, respectively). Conclusion: KIF20A expression is an independent prognostic factor for survival in patients with ER-positive BC who received adjuvant TAM therapy. In clinical practice, IHC evaluation of KIF20A expression in surgical samples before administering tamoxifen may assist in predicting the treatment outcomes of these patients.
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Background: Patients with advanced breast cancer usually have poor prognosis. Apatinib is a small-molecule tyrosine kinase inhibitor, and the reports regarding the efficacy and safety of apatinib monotherapy for advanced breast cancer in the current literature are controversial. Therefore, we performed a systematic review and meta-analysis to collect and pool efficacy and safety data of apatinib monotherapy for advanced breast cancer with the aim of providing up-to-date evidence to aid clinical practice. Methods: This study was registered at PROSPERO (CRD42020190049). Three literature databases, including PubMed, EMBASE, and Cochrane Library, were searched. For evaluating efficacy, the objective response rate and disease control rate were extracted or calculated. Safety was evaluated in terms of the proportions of patients with grade 3 or 4 treatment-related adverse events. The pooled proportions of the outcomes and their 95% confidence interval were shown. The Kaplan-Meier curves of overall survival and progression-free survival were pooled from the extracted data of the included studies. Furthermore, pooled medians for overall survival and progression-free survival were calculated. A p-value of < 0.05 was considered statistically significant. Results: Six studies were included and deemed eligible for further quality evaluation and analysis. The pooled objective response rate and disease control rate were 20.4% and 71.6%, respectively. The pooled proportions of four hematologic adverse events ranged from 2.6% to 6.9%. The pooled proportions of hypertension, hand-foot syndrome, transaminase increased, and proteinuria ranged from 4.1% to 24.3%, and other non-hematologic adverse events were <1%. The pooled median progression-free survival and overall survival were 4.00 and 10.43 months, respectively, in cases of advanced breast cancer treated with apatinib. Conclusions: This study confirms the reliable efficacy of apatinib monotherapy for advanced breast cancer. However, non-hematologic grade 3-4 adverse events, especially hypertension, are more frequently observed during apatinib treatment than during treatment with other tyrosine kinase inhibitors, such as sunitinib or sorafenib. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42020190049.
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This study aimed to investigate the effect and potential modulation mechanism of lnc-SLC4A1-1 on breast cancer (BC) carcinogenesis. The expression of lnc-SLC4A1-1 in tissue and serum samples from BC patients, as well as BC cell lines, was detected by real-time quantitative reverse transcription-polymerase chain reactions (qRT-PCRs). Next, the expression of lnc-SLC4A1-1 was silenced or upregulated in BC cells, then cell proliferation, apoptosis, migration and invasion were detected using MTT, flow cytometry analysis and Transwell assay. Meanwhile, the expression of apoptosis-related proteins and epithelial-mesenchymal transition-related proteins were detected by western blotting. Furthermore, potential mechanism of lnc-SLC4A1-1 was explored by chromatin immunoprecipitation and RNA immunoprecipitation assays. CXCL8 was overexpressed to evaluate the relationship between lnc-SLC4A1-1 and CXCL8. Lnc-SLC4A1-1 was significantly up-regulated in BC tissue, serum samples and cell lines. In BC cells, lnc-SLC4A1-1 knockdown promoted cell apoptosis and suppressed cell proliferation, migration and invasion. Furthermore, lnc-SLC4A1-1 is transcriptionally activated by H3K27 acetylation, and lnc-SLC4A1-1 interacted with transcription factor (NF)-κB p65, thereby regulating CXCL8 expression. Meanwhile, CXCL8 overexpression partly reversed the effects of lnc-SLC4A1-1 knockdown on cell viability, apoptosis, migration and invasion in BC cells. Lnc-SLC4A1-1 could promote the development of BC by regulating NF-κB/CXCL8. Highlights Lnc-SLC4A1-1 was overexpressed in BC tissues, blood and cell lines. Lnc-SLC4A1-1 was transcriptionally activated by H3K27 acetylation. Lnc-SLC4A1-1 interacted with NF-κB to promote CXCL8 expression. Lnc-SLC4A1-1 could promote the development of BC.