Objective To genetically investigate the protective effects of statins on breast cancer.Methods In-strumental variables for the statin target gene HMGCR and five other cholesterol-regulated genes(LDLR,PCSK9,ABCG8,APOB,and NPC1L1)were obtained from previous expression quantitative trait locus(eQTL)studies.Cholesterol-regulated genes predicted by these instrumental variables served as the exposure factors.Mendelian randomization based on pooled data(SMR)was conducted to explore the genetic effects of exposure factors on the incidence risk of all breast cancers,ER+breast cancer,and ER-breast cancer.Instrumental variables for total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),and non-high-density lipoprotein cholesterol(non-HDL-C)were derived from a previous human genome-wide association study and restricted to be chromosomally located within 100 kb of the above cholesterol regulatory genes;the instrumental variables could predict TC,LDL-C,or non-HDL-C levels under the regulation of the abovementioned cholesterol-associated genes which were used as exposure factors.Two-sample Mendelian randomization(IVW,MR-PRESSO,and MR-Egger)was used to explore the genetic effects of exposure factors on the risk of all breast cancers,ER+breast cancer,and ER-breast cancer.Results SMR analysis reported that elevated HMGCR expression was significantly associated with the increased incidence risk of all breast cancers and ER+breast cancer(P=0.044 and P=0.039,respectively)but not with the change in incidence risk of ER-breast cancer(P=0.190);the other five regulatory genes were not significantly correlated with the change in incidence risk of all breast cancers,ER+breast cancer,and ER-breast cancer(all P>0.05).IVW analysis reported that under the regulation of HMGCR,elevated levels of peripheral TC,LDL-C,and non-HDL-C significantly increased the incidence risk of all breast cancers(P=1.160e-05,P=1.248e-05,and P=1.869e-05)and the incidence risk of ER+breast cancer(P=3.181e-04,P=2.231e-04,and P=3.520e-04),but they were not associated with a change in the incidence risk of ER-breast cancer(P=0.062,P=0.133,and P=0.055).The results of MR-PRESSO and MR-Egger analyses supported the IVW results.Conclusion Statins could reduce the incidence risk of ER+breast cancer at the genetic level,but there is no such protective effects on ER-breast cancer.

Objective:To investigate the effect of miR-503 targeting CBX2 on drug resistance of breast cancer MDA-MB-231 cells and its potential mechanism.Methods:miR-con group, miR-503 group, si-con group, two groups of si-chromosome homologues (CBX), anti-miR-con group, anti-miR-503 group, miR-503+pcDNA group, miR-503+pcDNA-CBx2 group were set up. Real-time quantitative fluorescence polymerase chain reaction (qRT-PCR) was used to detect the expression levels of miR-503 and CBX2 mRNA. Western blot was used to detect protein expression. Cell activity was detected by MTT assay. The targeted regulatory relationship was detected by double luciferase assay.Results:Compared with normal breast cells HBL-100 (1.02±0.09), the expression level of miR-503 in breast cancer cells MCF-7 (0.41±0.05), MDA-MB-231 (0.25±0.03) and BT474 (0.35±0.04) was significantly decreased. The expression levels of CBX2 mRNA in MCF-7, MDA-MB-231 and BT474 cells were (4.02±0.35), (4.62±0.36) and (3.47±0.33), respectively. The expression levels of CBX2 protein in MCF-7, MDA-MB-231 and BT474 cells were (0.64±0.07), (0.74±0.05) and (0.68±0.06), respectively. The mRNA and protein contents of CBX2 in normal breast cells HPL-100 were (1.01±0.08) and (0.40±0.04), respectively, and the expression of CBX2 in breast cancer cells was significantly higher than that in normal breast cells ( P<0.05). Overexpression of miR-503 (3.64± 0.30) and silting of CBX2 inhibited proliferation, migration and invasion of MDA-MB-231 cells, and inhibited CBX2 (0.26±0.03), cyclin-dependent kinases, CDK) 4 (0.32± 0.03), Cyclin (CCN) D1 (0.58±0.03), matrix metalloproteinases (matrix metalloproteinases), MMP-2 (0.32±0.03) and MMP-9 (0.32±0.04) ( P<0.05). miR-503 targeted the expression of CBX2, and overexpression of CBX2 (0.75±0.03) could reverse the proliferation and drug resistance of miR-503 to MDA-MB-231 breast cancer cells. Conclusion:miR-503 may inhibit the proliferation, migration and invasion of breast cancer cells by down-regulating the expression of CBX2.

目的 探讨Encor、Mammotome及Hologic 3种真空辅助旋切系统在超声引导下乳腺微创旋切术应用中的差异.方法 收集2020年2月1日至2020年9月30日郑州大学第一附属医院乳腺外科收治的2 528例乳腺肿块手术患者的资料,选取临床资料及随访资料完整的患者共1 019例,按使用系统分为Encor组379例(病灶548个)、Mammotome组362例(病灶513个)及Hologic组278例(病灶433个).回顾分析比较3组病理结果、肿块大小、肿块切除率、手术时间、术中出血量、术后并发症情况及患者对手术满意度.结果 3组患者在病理结果、肿块切除率和术后并发症方面比较,差异无统计学意义(P＞0.05).Hologic系统切除肿块最大直径[13(10,18)mm]大于Encor系统[12(9,16)mm]和Mammotome系统[11(8,15)mm],差异有统计学意义(P＜0.05).Hologic 组手术时间[11.5(7,18)min]短于 Encor 组[27(18,38)min]及 Mammotome 组[24(18,32)min],差异有统计学意义(P＜0.05).Mammotome 组术中出血量[2.5(2,5)mL]少于Encor组[3(2,5)mL]及Hologic组[5(4,10)mL],差异有统计学意义(P＜0.05).Encor系统术后满意度(97.89％)高于 Mammotome 组(96.13％)及 Hologic 组(94.96％),差异有统计学意义(P＜0.05).结论 Encor、Mammo-tome及Hologic均是有效安全的微创旋切系统.Encor系统术后满意度高,但手术时间长.Mammotome系统术后出血量少,但切除肿块较小.Hologic系统切除肿块较大且手术时间短,但术中出血量较多,术后满意度较差.合适的选择将使旋切技术在乳腺手术中得到更有效的应用.

Background:Ultrasound diagnosis is a highly specific tool and widely applied, but is associated with low sensitivity in detection of sentinel lymph nodes (SLNs). The diagnostic value of routine ultrasound combining magnetic resonance lymphangiography (MRL) for the detection of SLNs in breast cancer metastasis is still unclear. This study used ultrasound combined with MRL to explore the diagnostic value of detecting SLN metastasis in breast cancer.Methods:This study included female breast cancer patients who received modified radical mastectomy at the Department of Breast Surgery, the First Affiliated Hospital of Zhengzhou University between January 2016 and January 2019. The gold standard of SLNs is pathological results. The patients were divided into three groups: (I) Group A: an ultrasound plus MRL (contrast agent injected outside the areola) group; (II) Group B: an ultrasound plus MRL (contrast agent injection around the areola) group; and (III) Group C: an ultrasound plus MRL group (this group comprised patients from the two aforementioned groups).Results:A total of 432 patients were included. The overall detection rate and overall diagnostic accuracy of SLNs in breast cancer differed significantly among the three groups (all P<0.05). Ultrasound plus MRL showed a best overall detection rate 56.02%, and a best diagnostic accuracy 95.83%. The detection rate and diagnostic accuracy of axillary SLNs varied markedly among the three groups (P<0.05). The detection rate and diagnostic accuracy when the internal mammary node was the SLN differed notably between the ultrasound plus MRL (contrast agent injected outside the areola) and ultrasound plus MRL (contrast agent injection around the areola) groups and between the ultrasound plus MRL (contrast agent injection around the areola) and ultrasound plus MRL groups (all P<0.05).Conclusions:Ultrasound plus MRL may be advantageous for the detection of SLN metastasis in breast cancer and predicting breast cancer prognosis.

Dendritic cells (DCs) are recognized as the most potent antigen-presenting cells, capable of priming both naïve and memory T cells. Thus, tumor-resident DCs (tumor-associated DCs: TADCs) play a crucial role in the immune response against tumors. However, TADCs are also well known as a "double-edged sword" because an immunosuppressive environment, such as a tumor microenvironment, maintains the immature and tolerogenic properties of TADCs, resulting in the deterioration of the tumor. Therefore, it is essential to maintain and enhance the anti-tumoral activity of TADCs to aid tumor elimination. This study demonstrated the potential for tumor growth inhibition of Aureobasidium pullulan-derived β-glucan (AP-BG). Administration of AP-BG dramatically limited the development of different types of tumor cell lines transplanted into mice. Examination of the tumor-infiltrating leukocytes revealed that AP-BG caused high expression of co-stimulatory molecules on TADCs and enhanced the production of cytolytic granules as well as pro-inflammatory cytokines by the tumor-resident T cells. Furthermore, the syngeneic mixed lymphoid reaction assay and popliteal lymph node assay showed the significant ability of AP-BG to improve DCs' antigen-specific priming of T cells in vitro and in vivo. Taken together, β-glucan might be an immune-potentiating adjuvant for cancer treatment. This highly widely-used reagent will initiate a new way to activate DC-targeted cancer immune therapy.

The prognostic value of the systemic immune-inflammation index (SII) in patients with pancreatic cancer is conflicting according to previous investigations. Therefore, we performed a meta-analysis to explore the association between SII and pancreatic cancer prognosis. Electronic databases were searched for studies exploring the association of SII with prognostic outcomes in pancreatic cancer. The endpoints were overall survival (OS), disease-free survival (DFS), recurrence-free survival (RFS), progression-free survival (PFS), cancerspecific survival (CSS), and clinicopathological parameters. The prognostic value of SII was estimated by hazard ratio (HR) or odds ratio (OR) with a 95% confidence interval (CI). Nine studies containing 11 cohorts with 2,365 subjects in total were included in this meta-analysis. Elevated SII was associated with poor OS (HR=1.50, 95% CI=1.15-1.96, p=0.002), RFS/PFS/DFS (HR=1.52, 95% CI=1.01-2.28, p=0.045), and CSS (HR=2.60, 95% CI=1.65-4.09, p < 0.001) in patients with pancreatic cancer. Additionally, there was no significant association between SII and other parameters in pancreatic cancer such as sex, tumor location, lymph node metastasis, tumor-nodemetastasis stage, vascular invasion, and grade. This meta-analysis suggested that elevated SII was a significant prognostic marker for short-term and long-term survival outcomes in patients with pancreatic cancer.

目的 分析乳腺癌骨转移患者的临床病理特征,构建乳腺癌骨转移发生的预测模型.方法 回顾性分析2019年6月1日至2019年12月31日郑州大学第一附属医院收治的201例乳腺癌患者的临床资料.根据首次转移部位,将其分为骨转移组与非骨转移组.通过t检验、Mann-Whitney U检验、χ2检验分析各临床病理特征与患者发生骨转移之间的关系.采用logistic回归筛选变量构建预测模型,并制作列线图.采用受试者操作特征曲线(ROC曲线)评估该模型的可靠性.结果 单因素分析结果 显示,淋巴结转移情况、激素受体状态、Ki-67、pS2、CK5/6、TOP-Ⅱ、P53及E-cadherin表达差异有统计学意义(P<0.05).多因素分析结果 显示,患者有淋巴结转移(OR=3.115,95％CI:0.992～9.785,P=0.043)、Ki-67高表达(OR=1.993,95％CI:1.975～2.012,P=0.032)、pS2表达阴性(OR=0.040,95％CI:0.040～0.430,P=0.002)、P120表达阴性(OR=0.261,95％CI:0.078～0.877,P=0.025)、E-cadherin表达阴性(OR=0.129,95％CI=0.037～0.455,P=0.001)及TOP-Ⅱ高表达(OR=1.491,95％CI:1.620～1.020,P=0.001)是患者发生骨转移的独立危险因素,也是构建列线图的显著变量.该列线图通过了校正和验证步骤,训练组和验证组的曲线下面积(AUC)分别为0.767和0.855.结论 该模型是预测乳腺癌患者骨转移的可靠工具,有助于临床医生为患者提供更加准确的决策依据并优化治疗方案.

Objective:To explore the role and possible mechanism of receptor-interacting serine/threonine protein kinase 4 (RIPK4) in the occurrence and development of breast cancer.Methods:The expression of RIPK4 protein in 96 cases of breast cancer and adjacent normal tissues was detected by immunohistochemistry, and the relationship between the expression of RIPK4 protein and the clinicopathological features of breast cancer was also analyzed. Small interfering RNA (siRNA) targeting RIPK4 was transiently transfected into breast cancer cell lines: MCF-7 and MDA-MB-231, beside the experimental group, there are also the blank control group and the negative siRNA transfection group. Western blotting was used to detect the inhibitory effects of these siRNAs. Cell counting kit-8 (CCK-8) and transwell assays were used to detect the effects of RIPK4 siRNA on the proliferation, invasion and metastasis abilities of MCF-7 and MDA-MB-231 cells. Western blotting was also used to detect the effects of RIPK4 siRNA on Wnt/β-catenin signaling pathway.Results:Immunohistochemistry showed that the expression of RIPK4 was significantly higher in breast cancer tissues (71.9%, 69/96) than that in normal tissues (21.9%, 21/96) and the differences were statistically significant ( χ2=48.188, P<0.01). The abnormal expression of RIPK4 was positively correlated with TNM stage, histological type and lymph node metastasis in breast cancer ( χ2=17.524, 40.697, 9.458, P<0.05). SiRNA targeting RIPK4 could inhibit the expression of RIPK4 protein in breast cancer cell lines: MCF-7 and MDA-MB-231. CCK-8 and transwell assays also showed that the proliferation, invasion and metastasis abilities of MCF-7 and MDA-MB-231 cells were decreased greatly after transfection with RIPK4 siRNA. Additionally, the expression of β-catenin and Vimentin in Wnt/β-catenin signaling pathway was decreased, and that of E-cadherin was increased in MCF-7 and MDA-MB-231 cells after transfection with RIPK4 siRNA. Conclusion:The expression of RIPK4 protein was abnormally high in breast cancer tissues. Inhibiting the expression of RIPK4 protein reduced the proliferation, invasion and metastasis of breast cancer cells by suppressing the occurrence of Wnt/β-catenin signal pathway related epithelial-mesenchymal transition.

目的 分析不同分子类型乳腺癌患者再发子宫常见良恶性肿瘤的发病率.方法 回顾性分析2015年2月至2019年2月郑州大学第一附属医院乳腺外科和妇科收治的362例乳腺癌患者的临床资料,对不同分子分型乳腺癌患者再发子宫常见良恶性肿瘤的发病率进行统计分析.结果 362例乳腺癌患者中,合并子宫内膜癌21例,宫颈癌14例,子宫肌瘤91例.4种分子分型乳腺癌患者再发子宫良恶性肿瘤发病率比较,差异有统计学意义(均P<0.05).Luminal A型乳腺癌患者再发子宫良恶性肿瘤发病率高于其他3型,差异有统计学意义(均P<0.05).其他3型乳腺癌患者再发子宫良恶性肿瘤发病率比较,差异无统计学意义(均P>0.05).结论不同分子分型乳腺癌患者再发子宫常见良恶性肿瘤的发病率存在差异,针对女性乳腺癌患者,应格外重视对妇科疾病的排查,尤其Luminal A型乳腺癌患者更易再发子宫疾病.

目的 探讨上皮钙黏素(E-cadherin)和人类表皮生长因子受体2(Her-2)在Luminal B型乳腺癌组织中的表达及临床意义.方法 收集2017年10月至2019年1月在郑州大学第一附属医院接受改良根治术的146例Luminal B型乳腺癌患者的临床资料.采用免疫组织化学方法 检测癌组织E-cadherin、Her-2的表达情况.分析E-cadherin、Her-2在Luminal B型乳腺癌的表达特点及与临床病理特征的关系.结果 E-cadherin表达与组织学分类和TNM分期有关(均P<0.05).Her-2与原发肿瘤直径、组织学分类和淋巴结转移数目有关(均P<0.05).在Luminal B型乳腺癌组织中,E-cadherin表达与Ki-67、Her-2表达呈正相关(均P<0.05).在Luminal B乳腺癌组织中,Her-2表达与PR表达呈负相关(P<0.05),与Ki-67表达呈正相关(P<0.05).结论 在Lu-minal B型乳腺癌中,E-cadherin低表达者和Her-2阳性表达者更容易出现肿瘤细胞的侵袭转移,促使Luminal B型乳腺癌恶性生物行为的发生.

Breast cancer (BC) is a frequently diagnosed malignancy in women. Increasing evidence implicates mis-expression of the long non-coding RNA (lncRNA) RHPN1 antisense RNA 1 (RHPN1-AS1) in the development of multiple cancer types. However, little is known about the expression pattern and function of lncRNA RHPN1-AS1 in the pathobiology of BC. We evaluated the expression of RHPN1-AS1 in The Cancer Genome Atlas dataset, and analyzed associations between RHPN1-AS1 expression and clinicopathologic features of BC patients. Additionally, we compared the expression of RHPN1-AS1 between BC and breast non-tumor samples via quantitative real-time polymerase chain reaction, and in situ hybridization, and evaluated the prognostic value of RHPN1-AS1 in a BC tissue microarray. We examined the impact of RHPN1-AS1 knockdown on proliferation, migration, and invasion of BC cells in vitro, and tumor growth in vivo. Bioinformatics analyses were used to predict the function of RHPN1-AS1 in BC. RHPN1-AS1 expression was upregulated in BC and elevated RHPN1-AS1 expression was strongly associated with poor prognosis of BC patients. Moreover, both univariate and multivariate analyses revealed that RHPN1-AS1 was a significant and independent predictor of BC prognosis. Functionally, RHPN1-AS1 silencing attenuated BC cell proliferation, migration, and invasion in vitro, and reduced tumor growth in xenograft models. Furthermore, RHPN1-AS1 silencing was associated with a decrease in the expression of epithelial-to-mesenchymal transition (EMT) markers in the xenograft tumors, suggesting that RHPN1-AS1 promotes invasion in BC cells by enhancing EMT. These findings suggest that RHPN1-AS1 is a potential prognostic biomarker and therapeutic target for BC.

目的 总结近年来乳腺Paget病特点.方法 回顾性分析郑州大学第一附属医院2011年10月至2017年12月123例乳腺Paget病患者的入院情况、手术方式、病理特点.结果 患者发病年龄26～86岁,平均(52.6±11.0)岁.发病时间3 d～20 a,中位发病时间为1 a.就诊原因中,以皮肤病变就诊占70.7％(87/123),肿块就诊占18.7％(23/123),合并病变占10.6％(13/123).术前彩超发现肿块占41.5％(49/118),其他回声异常占28.8％(34/118),合并异常占13.6％(16/118),无明显异常占16.1％(19/118).手术方式中,保乳术占3.3％(4/123),改良根治术占52.0％(64/123),单纯切除术占44.7％(55/123).病理结果中单纯乳腺Paget病占9.8％(12/123),乳腺Paget病合并导管原位癌占29.3％(36/123),乳腺Paget病合并浸润癌占60.9％(75/123).免疫组化表现为ER、PR低表达,Her-2高表达,Ki-67<15％占9.6％(11/115),Ki-6715％ ～30％占18.5％(21/115),Ki-67≥30％占72.2％(83/115).淋巴结转移占15.4％(19/123).根据是否伴有浸润将病例分为非浸润癌和浸润癌两组,两组肿块、淋巴结比例比较,差异有统计学意义(P<0.05);两组ER、PR、HER-2、Ki-67的表达比较,差异无统计学意义(P>0.05).结论 乳腺Paget病有其独特的临床特征,病程进展缓慢,ER、PR呈低表达,Her-2、Ki-67呈高表达;早期乳腺彩超对乳腺Paget病的分期较为重要.

Introduction: Long non-coding RNAs (lncRNAs) are key regulators in multiple cancers. lncRNA, SNHG1, was shown to be associated with tumorigenesis. However, little is known about the role SNHG1 plays in breast cancer. The aim of the study was to study the role and underlying mechanism of SNHG1 regulation in breast cancer. Methods: Quantitative real-time PCR was used to measure the levels of SNHG1, miR-382 and ZEB1 levels in breast cancer tissue or cells. The proliferation, colony formation, migration and invasion of breast cancer cells, under SNHG1 knockdown achieved by transfection of SNHG1-specific siRNAs, were assessed by Cell Counting Kit-8, colony forming, scratch wound and transwell assays. Bioinformatical analysis and luciferase assay were used to explore the interaction between SNHG1 and its potential miRNA target. Western blot was used to evaluate the expression of epithelial-to-mesenchymal transition (EMT) markers. MDA-MB-231 cells with or without SNHG1 knockdown were used to initiate tumor xenografts in vivo. Tumor growth and expression of SNHG1, miR-382-5p and EMT markers were evaluated. Results: SNHG1 upregulation was observed in breast cancer tissues and cells. Knockdown of SNHG1 attenuated breast cancer proliferation, colony formation, migration and invasion. A miRNA, miR-382-5p, was identified as the target of SNHG1. A reciprocal negative regulation was found between SNHG1 and miR-382-5p. SNHG1 knockdown attenuated EMT both in vitro and in vivo. miR-382-5p transfection reversed the tumor-promoting role by SNHG1. In vivo, SNHG1 knockdown decreased breast tumor growth. Conclusion: SNHG1 promotes breast cancer through the regulation of miR-382-5p and EMT markers. Our results report SNHG1 as a novel miRNA that govern the progression of breast cancer, providing a potential new therapeutic target in breast cancer.

Department of Breast Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan Province 450052, China Introduction: Long non-coding RNAs (lncRNAs) are key regulators in multiple cancers. lncRNA, SNHG1, was shown to be associated with tumorigenesis. However, little is known about the role SNHG1 plays in breast cancer. The aim of the study was to study the role and underlying mechanism of SNHG1 regulation in breast cancer. Methods: Quantitative real-time PCR was used to measure the levels of SNHG1, miR-382 and ZEB1 levels in breast cancer tissue or cells. The proliferation, colony formation, migration and invasion of breast cancer cells, under SNHG1 knockdown achieved by transfection of SNHG1specific siRNAs, were assessed by Cell Counting Kit-8, colony forming, scratch wound and transwell assays. Bioinformatical analysis and luciferase assay were used to explore the interaction between SNHG1 and its potential miRNA target. Western blot was used to evaluate the expression of epithelial-to-mesenchymal transition (EMT) markers. MDA-MB-231 cells with or without SNHG1 knockdown were used to initiate tumor xenografts in vivo. Tumor growth and expression of SNHG1, miR-382-5p and EMT markers were evaluated. Results: SNHG1 upregulation was observed in breast cancer tissues and cells. Knockdown of SNHG1 attenuated breast cancer proliferation, colony formation, migration and invasion. A miRNA, miR-382-5p, was identified as the target of SNHG1. A reciprocal negative regulation was found between SNHG1 and miR-382-5p. SNHG1 knockdown attenuated EMT both in vitro and in vivo. miR-382-5p transfection reversed the tumor-promoting role by SNHG1. In vivo, SNHG1 knockdown decreased breast tumor growth. Conclusion: SNHG1 promotes breast cancer through the regulation of miR-382-5p and EMT markers. Our results report SNHG1 as a novel miRNA that govern the progression of breast cancer, providing a potential new therapeutic target in breast cancer.

目的 探讨Ki-67水平对乳腺癌骨转移患者预后的影响.方法 回顾性分析2009年6月至2015年6月郑州大学第一附属医院收治的347例乳腺癌骨转移患者的临床资料,包括确诊乳腺癌骨转移时的年龄、原发肿瘤大小、组织学分级、有无其他部位转移、Ki-67、雌激素受体(ER)、孕激素受体(PR)、人表皮生长因子受体-2(HER2)、骨转移前无进展生存期(PFS)、骨转移后无进展生存期(BM-PFS)和骨转移后总生存期(BM-OS)等.利用统计学软件分析相关指标与预后的关系.结果 Ki-67水平与骨转移前PFS有关(P<0.05).Ki-67(-)组BM-PFS分别与Ki-67(+)组、Ki-67(++)组比较,差异无统计学意义(P>0.05).Ki-67(++)组BM-PFS较Ki-67(+)组短,Ki-67(+++)组BM-PFS较Ki-67(-)组、Ki-67(+)组、Ki-67(++)组短,差异有统计学意义(均P<0.05).Ki-67低表达组BM-OS较Ki-67高表达组长,差异有统计学意义(P<0.05).PR阴性、PFS≤2 a、存在其他转移、多发骨转移是影响乳腺癌骨转移患者BM-OS的独立危险因素(P<0.05).结论 Ki-67高表达的乳腺癌患者易较早发生骨转移,骨转移后疾病控制效果较差.Ki-67高表达的乳腺癌患者BM-OS较短.PR阴性、PFS≤2 a、多发骨转移、伴有其他转移是乳腺癌骨转移患者预后不良的独立危险因素.

Breast cancer is the second leading cause of cancer-related death among women worldwide. Emerging evidence suggests that chromobox homolog 2 (CBX2) is overexpressed in breast cancer and plays an essential role in tumor progression. However, its expression and functional roles in breast cancer development and progression require further exploration. Here, we evaluated CBX2 expression in breast cancer using mRNA expression data from the TCGA database; CBX2 expression was upregulated in breast cancer. Furthermore, upregulated CBX2 expression was significantly associated with poorer overall survival (OS) and progression-free survival (PFS) of breast cancer patients. Immunohistochemical analysis of CBX2 expression in a tissue microarray (TMA) cohort yielded concordant results. Univariate and multivariate analyses showed that elevated CBX2 expression was significantly and independently associated with poorer OS of patients in this TMA cohort. Additionally, we performed in vitro functional assays to evaluate the proliferation, migration, and invasion abilities of breast cancer cell lines wherein CBX2 was knocked down using short hairpin RNA (shRNA). CBX2 silencing inhibited cell proliferation, migration, and invasion in vitro. Furthermore, knockdown of CBX2 markedly reduced breast tumorigenesis in xenograft mouse models. Functional and pathway enrichment analyses indicated a positive correlation between high CBX2 expression and activation of the PI3K/AKT pathway, which were further confirmed by western blot and immunohistochemical analyses of mouse tumors. Our findings indicate that CBX2 is a potential prognostic biomarker and therapeutic target for breast cancer.

PURPOSE:Long-chain noncoding RNAs (lncRNAs) are involved in regulating the sensitivity of cancer cells to chemotherapeutic drugs, but the specific mechanism of action is not well understood. The aim of this study was to investigate the effect of lncRNA growth-stasis specific transcript 5 (GAS5) on triple-negative breast cancer (TNBC).METHODS:Quantitative real-time polymerase chain reaction and flow cytometry were used to screen lncRNA associated with tumor resistance. Double luciferase reporter gene assay, flow cytometry, and Western blot assay were used to determine whether miRNA 378a-5p and SUFU were involved in tumor cell apoptosis induced by lncRNA GAS5. A mouse model of subcutaneous xenografts was established to investigate the relationship between lncRNA GAS5 and tumor resistance in vivo.RESULTS:In this study, the expression of lncRNA GAS5 was significantly downregulated in cells treated with paclitaxel (PTX) or cisplatin (CIS). Furthermore, TNBC cells with low expression of lncRNA GAS5 had a lower percentage of apoptosis under stress conditions, especially in serum-free medium. More interestingly, the expression level of lncRNA GAS5 in TNBC patients was associated with tumor resistance to PTX and CIS. In addition, RNA immunoprecipitation experiments confirmed that lncRNA GAS5 and miR-378 could directly bind to each other. Moreover, the miR-378a-5p target of SUFU could promote lncRNA GAS5-induced apoptosis of TNBC cells. Finally, lncRNA GAS5 overexpressed MDA-231R could enhance the sensitivity of TNBC to PTX.CONCLUSION:The above results confirmed that lncRNA GAS5 could induce apoptosis in TNBC cells by targeting miR-378a-5p/SUFU signaling.

Aims: Increasing evidence links the abnormal expression of microRNAs and ATP-binding cassette subfamily C member 4 (ABCC4) with tumor development and progression, as well as with chemoresistance. Our aims were to determine the therapeutic potential of targeting both miR-124-3p and ABCC4 in breast cancer cells and to determine if duel targeting increased their sensitivity to chemotherapeutic drugs, in vitro. Materials and Methods: The expression of the ABCC4 protein and miR-124-3p were detected, respectively, by immunohistochemical staining and quantitative real-time polymerase chain reaction in breast cancer tumor tissue, MCF-7 and MCF-7-ADR cell lines. Suppression of ABCC4 expression and miR-124-3p overexpression were performed in MCF-7-ADR cell lines. Western blot assays were used to detect expression of ABCC4 and permeability glycoprotein 1/multi-drug resistance protein 1 (P-gp) in cells. Cell Counting Kit-8, flow cytometry, transwell, and scratch assays were conducted to detect cell proliferation, cell cycle, invasion, and migration of cells. Results: We found that ABCC4 protein expression was significantly increased, while the miR-124-3p level was significantly decreased in breast cancer tissue and cell lines. Tumor size and clinical tumor node metastasis stage were significantly correlated with elevated expression of ABCC4 and decreased expression of miR-124-3p. Interestingly, ABCC4 expression was significantly increased in MCF-7-ADR cells, while miR-124-3p level was significantly decreased compared with MCF-7 cells. The inhibition of ABCC4 and miR-124-3p overexpression both led to a significant decrease in cell proliferation, invasion, and migration of MCF-7-ADR cells, and combination of suppression of ABCC4 with miR-124-3p overexpression had a synergistic inhibitory effect. Our results further demonstrated that inhibition of ABCC4 expression and overexpression of miR-124-3p significantly enhanced the sensitivity to adriamycin (ADR) in MCF-7-ADR cells, and that simultaneous dual-targeting of miR-124-3p and ABCC4 had a stronger promotive effect on the sensitivity to ADR in MCF-7-ADR cells. Moreover, western blot analysis showed that miR-124-3p overexpression significantly inhibited P-gp expression in MCF-7-ADR cells. Conclusion: Our data demonstrate that the combination of downregulation of ABCC4 with overexpression of miR-124-3p significantly increased sensitivity to ADR in MCF-7-ADR cells. This finding suggests that similar dual targeting may serve as a means to enhance therapies for drug-resistant breast cancers.

e12017 Background: Adjuvant docetaxel-based chemotherapy is frequently used for operable breast cancer. This study investigated the patterns of use of docetaxel (T) in real-life clinical practice in China. Methods: This retrospective pooled analysis included female Chinese adults (≥18 years) with operable breast cancer treated with docetaxel-based adjuvant chemotherapy enrolled in the Asia-Pacific Breast Initiatives (APBI) I (2006-2008) and II (2009-2011) registries, and two Chinese observational studies; BC STATE (2011-2014) and BC Local Registry (2007-2010). Patients with metastatic disease were excluded. The primary endpoint was assessment of treatment patterns and patient profiles. Patient profiles for treatment regimen selection were investigated using regression analysis. Results: Data from 3020 patients were included. The most commonly used regimen was docetaxel/anthracycline combination (n=1421 [47.1%]; of whom 52.0% received T/epirubicin (E)/cyclophosphamide (C)), followed by docetaxel/other (n=705 [23.3%]; of whom 72.8% received TC), docetaxel/anthracycline sequential (n=447 [14.8%]; of whom 40.9% and 39.6% received 5-Fu/EC-T and EC-T), and ‘Other’ (n=447 [14.8%]; of whom 91.5% received T). Multivariate regression analysis revealed a significant association between selection of docetaxel/anthracycline combination and patient weight, menopausal status, and estrogen receptor and HER-2 status (Table). Conclusions: Data from real clinical practice show docetaxel/anthracycline combination is the most commonly used docetaxel-based adjuvant therapy for operable breast cancer in China; of which TEC is the most popular specific regimen. Several patient profile factors were significantly associated with the selection of docetaxel/anthracycline combination. [Table: see text]