Dysregulation of post-transcriptional regulation of gene expression has been found to influence various human disorders. Aberrant miRNA-based regulation of gene expression has been found to be associated with differen...Dysregulation of post-transcriptional regulation of gene expression has been found to influence various human disorders. Aberrant miRNA-based regulation of gene expression has been found to be associated with different cancers, including breast cancers. Very little information is available on the effect of dysregulation of miRNA-mediated regulation on luminal B breast cancer. This study was aimed at comprehending the regulation of gene expression through miRNA in luminal B breast cancers by comprehensive analysis of miRNA and mRNA expression data together. Negatively regulated miRNA-target gene pairs were identified, and the target genes were functionally enriched to identify critical pathways associated with luminal B breast cancer. Further, the prognostic significance of these miRNAs and target gene pairs was assessed to identify genes with prognostic value in luminal B breast cancer. A total of 266 differentially expressed miRNAs and 164 dysregulated miRNA-target gene pairs were identified. Four genes, including SRP9, DSN1, RACGAP1, and SLC10A6, and one miRNA, hsa-mir-421, showed significant influence on the prognosis of patients with luminal B breast cancer. Through additional experimental examination of these findings, a deeper comprehension of miRNA-based post-transcriptional regulation in luminal B breast tumors will be possible.展开更多
乳腺癌是女性常见恶性肿瘤,男性相对少见[1]。男性乳腺癌(male breast carcinoma,MBC)在所有乳腺癌患者占比<1%,在男性所有癌症中占比<1%,但发病率呈缓慢上升趋势[2],临床上以中老年患者多见[3]。MBC发病率较低,发现时往往分期较...乳腺癌是女性常见恶性肿瘤,男性相对少见[1]。男性乳腺癌(male breast carcinoma,MBC)在所有乳腺癌患者占比<1%,在男性所有癌症中占比<1%,但发病率呈缓慢上升趋势[2],临床上以中老年患者多见[3]。MBC发病率较低,发现时往往分期较晚,恶性程度较高[4],缺乏特定治疗手段,预后较差[5]。临床上对于MBC的治疗建议通常参考女性乳腺癌的临床试验结果。本文报告1例Luminal B型MBC的诊治,并复习相关文献,为临床诊疗MBC提供参考。展开更多
Background:Luminal A breast cancer has the best prognosis of all malignant breast cancer types.In clinical practice,some patients with luminal A breast cancer present with small tumors(usually<20 mm)but with lymph ...Background:Luminal A breast cancer has the best prognosis of all malignant breast cancer types.In clinical practice,some patients with luminal A breast cancer present with small tumors(usually<20 mm)but with lymph node metastases or even distant organ metastasis.Owing to their insensitivity to chemotherapy and the lack of conclusive clinical evidence,there is a significant gap in research on luminal A breast cancer with high invasiveness.This study aimed to identify genes that drive the invasiveness of luminal A breast cancer and explore the underlying mechanisms.Methods:In this study,we first utilized bioinformatics techniques to analyze differentially expressed mRNAs and enrich common functional pathways to identify the target gene DDHD domain containing 2(DDHD2).We then evaluated the association between DDHD2 expression and patient prognosis,genetic material changes,and transcriptional,translational,and immune responses in luminal A breast cancer.We also conducted experiments at the molecular and cellular levels to validate these biochemical mechanisms.Results:The expression of DDHD2 varied between patients with low-grade luminal A breast cancer with and without lymph node metastases.Our findings demonstrated that DDHD2 exerted carcinogenic effects through various pathways by altering cell adhesion and migration,regulating cell proliferation and apoptosis cycles,and suppressing immune responses.Moreover,a pathway through which DDHD2 inhibited immunity was preliminarily verified.Conclusions:The results revealed a novel role for DDHD2 in promoting the malignant transformation and invasiveness of luminal A breast cancer.Considering its effects on the tumor microenvironment and tumor-infiltrating immune cells in the epithelial-mesenchymal transition,DDHD2 is proposed as a reliable direction for future immunotherapy and a potential target in luminal A breast cancer immune resistance.展开更多
目的:探讨GATA3与FOXA1在luminal亚型乳腺癌细胞中的相互作用。方法:基于cBioportal For Cancer Genomics公共数据库中乳腺癌临床病例数据集,分析luminal A、luminal B和basal-like亚型乳腺癌组织中GATA3与FOXA1mRNA表达水平的相关性;...目的:探讨GATA3与FOXA1在luminal亚型乳腺癌细胞中的相互作用。方法:基于cBioportal For Cancer Genomics公共数据库中乳腺癌临床病例数据集,分析luminal A、luminal B和basal-like亚型乳腺癌组织中GATA3与FOXA1mRNA表达水平的相关性;利用蛋白-蛋白相互作用数据库STRING和分析工具Cytoscape预测GATA3与FOXA1的相互作用。以luminal亚型的MCF-7和T-47D乳腺癌细胞以及basal-like亚型的MDA-MB-231和SUM-149PT乳腺癌细胞为研究对象,采用RT-qPCR和Western印迹检测GATA3和FOXA1的mRNA和蛋白表达水平;细胞免疫荧光检测GATA3和FOXA1的细胞定位;蛋白质免疫共沉淀验证GATA3与FOXA1之间的相互作用。结果:临床病例数据分析显示GATA3与FOXA1在luminal A、luminal B和basal-like亚型乳腺癌组织中mRNA的表达均呈正相关(r=0.4047、0.4761、0.5876,均P<0.0001)。蛋白质相互作用预测显示GATA3与FOXA1存在潜在的相互作用关系。Luminal乳腺癌细胞中GATA3和FOXA1的mRNA(t=80.95、79.73、33.84、33.60,均P<0.0001;t=15.24、5.21、14.95、14.93,均P<0.001)和蛋白(t=29.63、28.48、36.60、35.60,均P<0.0001;t=34.06、35.30、75.01、74.32,均P<0.0001)表达水平显著高于basal-like细胞。GATA3与FOXA1在MCF-7和T-47D细胞核中共定位。GATA3与FOXA1存在蛋白相互作用。结论:GATA3与FOXA1可能通过相互作用维持luminal亚型乳腺癌表型稳态,抑制肿瘤恶性进展。展开更多
Chondroitin sulfate synthase 2(CHPF)is characterized as an oncogenic and poor prognosis-related gene in breast cancer.However,this gene has alternative splicing products encoding proteins of different lengths.Breast c...Chondroitin sulfate synthase 2(CHPF)is characterized as an oncogenic and poor prognosis-related gene in breast cancer.However,this gene has alternative splicing products encoding proteins of different lengths.Breast cancer is a group of heterogeneous tumors with distinct clinical and genomic characteristics.In this study,we explored the expression profile and prognostic value of the two transcripts of CHPF using data from The Cancer Genome Atlas(TCGA)-BRCA.The functional regulation of the two transcripts was also studied in MCF-7 and BT-474 cells.Among the two transcripts of CHPF,ENST00000535926 expression was significantly upregulated in the tumor samples and was the dominant isoform.ENST00000535926,but not ENST00000243776 upregulation,was associated with significantly worse progression-free survival(PFS)and disease-specific survival(DSS)in luminal A/B cases.However,no significant association was observed in PFS or DSS in other Prediction Analysis of Microarray 50(PAM50)subgroups.CHPF isoform 2 protein(encoded by ENST00000535926)significantly elevated the expression of P3H1 and RCN3 at the mRNA and protein levels in MCF-7 and BT-474 cells.The effect of ENST00000535926 was significantly stronger than ENST00000243776 in promoting tumor cell colony formation.The expression of P3H1 and RCN3 was negatively correlated with CD8+T cell infiltration but was positively correlated with cancer-associated fibroblast infiltration in luminal A/B tumors.In summary,this study revealed that ENST00000535926 is an unfavorable prognosis-related and tumor-promoting transcript of the CHPF gene in luminal A/B breast cancer.展开更多
Endoscopic luminal stenting(ELS)represents a minimally invasive option for the management of malignant obstruction along the gastrointestinal tract.Previous studies have shown that ELS can provide rapid relief of symp...Endoscopic luminal stenting(ELS)represents a minimally invasive option for the management of malignant obstruction along the gastrointestinal tract.Previous studies have shown that ELS can provide rapid relief of symptoms related to esophageal,gastric,small intestinal,colorectal,biliary,and pancreatic neoplastic strictures without compromising cancer patients’overall safety.As a result,in both palliative and neoadjuvant settings,ELS has largely surpassed radiotherapy and surgery as a first-line treatment modality.Following the abovementioned success,the indications for ELS have gradually expanded.To date,ELS is widely used in clinical practice by well-trained endoscopists in managing a wide variety of diseases and complications,such as relieving non-neoplastic obstructions,sealing iatrogenic and non-iatrogenic perforations,closing fistulae and treating post-sphincterotomy bleeding.The abovementioned development would not have been achieved without corresponding advances and innovations in stent technology.However,the technological landscape changes rapidly,making clinicians’adaptation to new technologies a real challenge.In our mini-review article,by systematically reviewing the relevant literature,we discuss current developments in ELS with regard to stent design,accessories,techniques,and applications,expanding the research basis that was set by previous studies and highlighting areas that need to be further investigated.展开更多
Study of marine noctilucence in marine is important to fishery, environmental monitoring and military affairs. A luminous bacterial strain D2 was isolated from the marine sediment samples collected near Donghai Island...Study of marine noctilucence in marine is important to fishery, environmental monitoring and military affairs. A luminous bacterial strain D2 was isolated from the marine sediment samples collected near Donghai Island in Zhanjiang, China. The primary cultural and luminescent conditions of luminous bacterium D2 which was identified as Vibrio sp. were determined in liquid culture. The results showed that pH 7.0, 35 ℃, with 2.0 % NaCI, were the best growth conditions, and pH5 - 6, 20℃, OD600 0.08, with 3.0 % NaCI, were the optimal luminescent conditions.展开更多
文摘Dysregulation of post-transcriptional regulation of gene expression has been found to influence various human disorders. Aberrant miRNA-based regulation of gene expression has been found to be associated with different cancers, including breast cancers. Very little information is available on the effect of dysregulation of miRNA-mediated regulation on luminal B breast cancer. This study was aimed at comprehending the regulation of gene expression through miRNA in luminal B breast cancers by comprehensive analysis of miRNA and mRNA expression data together. Negatively regulated miRNA-target gene pairs were identified, and the target genes were functionally enriched to identify critical pathways associated with luminal B breast cancer. Further, the prognostic significance of these miRNAs and target gene pairs was assessed to identify genes with prognostic value in luminal B breast cancer. A total of 266 differentially expressed miRNAs and 164 dysregulated miRNA-target gene pairs were identified. Four genes, including SRP9, DSN1, RACGAP1, and SLC10A6, and one miRNA, hsa-mir-421, showed significant influence on the prognosis of patients with luminal B breast cancer. Through additional experimental examination of these findings, a deeper comprehension of miRNA-based post-transcriptional regulation in luminal B breast tumors will be possible.
文摘乳腺癌是女性常见恶性肿瘤,男性相对少见[1]。男性乳腺癌(male breast carcinoma,MBC)在所有乳腺癌患者占比<1%,在男性所有癌症中占比<1%,但发病率呈缓慢上升趋势[2],临床上以中老年患者多见[3]。MBC发病率较低,发现时往往分期较晚,恶性程度较高[4],缺乏特定治疗手段,预后较差[5]。临床上对于MBC的治疗建议通常参考女性乳腺癌的临床试验结果。本文报告1例Luminal B型MBC的诊治,并复习相关文献,为临床诊疗MBC提供参考。
基金funded by the National Natural Science Foundation of China(no.82103671).
文摘Background:Luminal A breast cancer has the best prognosis of all malignant breast cancer types.In clinical practice,some patients with luminal A breast cancer present with small tumors(usually<20 mm)but with lymph node metastases or even distant organ metastasis.Owing to their insensitivity to chemotherapy and the lack of conclusive clinical evidence,there is a significant gap in research on luminal A breast cancer with high invasiveness.This study aimed to identify genes that drive the invasiveness of luminal A breast cancer and explore the underlying mechanisms.Methods:In this study,we first utilized bioinformatics techniques to analyze differentially expressed mRNAs and enrich common functional pathways to identify the target gene DDHD domain containing 2(DDHD2).We then evaluated the association between DDHD2 expression and patient prognosis,genetic material changes,and transcriptional,translational,and immune responses in luminal A breast cancer.We also conducted experiments at the molecular and cellular levels to validate these biochemical mechanisms.Results:The expression of DDHD2 varied between patients with low-grade luminal A breast cancer with and without lymph node metastases.Our findings demonstrated that DDHD2 exerted carcinogenic effects through various pathways by altering cell adhesion and migration,regulating cell proliferation and apoptosis cycles,and suppressing immune responses.Moreover,a pathway through which DDHD2 inhibited immunity was preliminarily verified.Conclusions:The results revealed a novel role for DDHD2 in promoting the malignant transformation and invasiveness of luminal A breast cancer.Considering its effects on the tumor microenvironment and tumor-infiltrating immune cells in the epithelial-mesenchymal transition,DDHD2 is proposed as a reliable direction for future immunotherapy and a potential target in luminal A breast cancer immune resistance.
文摘目的:探讨GATA3与FOXA1在luminal亚型乳腺癌细胞中的相互作用。方法:基于cBioportal For Cancer Genomics公共数据库中乳腺癌临床病例数据集,分析luminal A、luminal B和basal-like亚型乳腺癌组织中GATA3与FOXA1mRNA表达水平的相关性;利用蛋白-蛋白相互作用数据库STRING和分析工具Cytoscape预测GATA3与FOXA1的相互作用。以luminal亚型的MCF-7和T-47D乳腺癌细胞以及basal-like亚型的MDA-MB-231和SUM-149PT乳腺癌细胞为研究对象,采用RT-qPCR和Western印迹检测GATA3和FOXA1的mRNA和蛋白表达水平;细胞免疫荧光检测GATA3和FOXA1的细胞定位;蛋白质免疫共沉淀验证GATA3与FOXA1之间的相互作用。结果:临床病例数据分析显示GATA3与FOXA1在luminal A、luminal B和basal-like亚型乳腺癌组织中mRNA的表达均呈正相关(r=0.4047、0.4761、0.5876,均P<0.0001)。蛋白质相互作用预测显示GATA3与FOXA1存在潜在的相互作用关系。Luminal乳腺癌细胞中GATA3和FOXA1的mRNA(t=80.95、79.73、33.84、33.60,均P<0.0001;t=15.24、5.21、14.95、14.93,均P<0.001)和蛋白(t=29.63、28.48、36.60、35.60,均P<0.0001;t=34.06、35.30、75.01、74.32,均P<0.0001)表达水平显著高于basal-like细胞。GATA3与FOXA1在MCF-7和T-47D细胞核中共定位。GATA3与FOXA1存在蛋白相互作用。结论:GATA3与FOXA1可能通过相互作用维持luminal亚型乳腺癌表型稳态,抑制肿瘤恶性进展。
基金supported by the Science and Technology Plan Project of Sichuan Province(Provincial Academy and Provincial University Cooperation Project)(2020YFSY0025).
文摘Chondroitin sulfate synthase 2(CHPF)is characterized as an oncogenic and poor prognosis-related gene in breast cancer.However,this gene has alternative splicing products encoding proteins of different lengths.Breast cancer is a group of heterogeneous tumors with distinct clinical and genomic characteristics.In this study,we explored the expression profile and prognostic value of the two transcripts of CHPF using data from The Cancer Genome Atlas(TCGA)-BRCA.The functional regulation of the two transcripts was also studied in MCF-7 and BT-474 cells.Among the two transcripts of CHPF,ENST00000535926 expression was significantly upregulated in the tumor samples and was the dominant isoform.ENST00000535926,but not ENST00000243776 upregulation,was associated with significantly worse progression-free survival(PFS)and disease-specific survival(DSS)in luminal A/B cases.However,no significant association was observed in PFS or DSS in other Prediction Analysis of Microarray 50(PAM50)subgroups.CHPF isoform 2 protein(encoded by ENST00000535926)significantly elevated the expression of P3H1 and RCN3 at the mRNA and protein levels in MCF-7 and BT-474 cells.The effect of ENST00000535926 was significantly stronger than ENST00000243776 in promoting tumor cell colony formation.The expression of P3H1 and RCN3 was negatively correlated with CD8+T cell infiltration but was positively correlated with cancer-associated fibroblast infiltration in luminal A/B tumors.In summary,this study revealed that ENST00000535926 is an unfavorable prognosis-related and tumor-promoting transcript of the CHPF gene in luminal A/B breast cancer.
文摘Endoscopic luminal stenting(ELS)represents a minimally invasive option for the management of malignant obstruction along the gastrointestinal tract.Previous studies have shown that ELS can provide rapid relief of symptoms related to esophageal,gastric,small intestinal,colorectal,biliary,and pancreatic neoplastic strictures without compromising cancer patients’overall safety.As a result,in both palliative and neoadjuvant settings,ELS has largely surpassed radiotherapy and surgery as a first-line treatment modality.Following the abovementioned success,the indications for ELS have gradually expanded.To date,ELS is widely used in clinical practice by well-trained endoscopists in managing a wide variety of diseases and complications,such as relieving non-neoplastic obstructions,sealing iatrogenic and non-iatrogenic perforations,closing fistulae and treating post-sphincterotomy bleeding.The abovementioned development would not have been achieved without corresponding advances and innovations in stent technology.However,the technological landscape changes rapidly,making clinicians’adaptation to new technologies a real challenge.In our mini-review article,by systematically reviewing the relevant literature,we discuss current developments in ELS with regard to stent design,accessories,techniques,and applications,expanding the research basis that was set by previous studies and highlighting areas that need to be further investigated.
文摘目的:探讨基于T_(2)WI、DCE磁共振影像组学模型对Luminal型乳腺癌分子分型的预测价值。方法:回顾性收集2018年1月—2021年10月昆明医科大学第一附属医院经病理证实的140例Luminal型乳腺癌,其中Luminal A型85例、Luminal B(HER-2阴性)型55例,病例按照7:3比例随机分为训练集和测试集。分别在T_(2)WI、DCE图像逐层勾画全病灶感兴趣区并提取影像组学特征。采用t检验和最小绝对缩减和变量选择算子(least absolute shrinkage and selection operator,LASSO)对影像组学特征降维并建立组学标签,通过逻辑回归分别对两个序列影像组学特征建模、训练并验证。应用受试者工作特征(receiver operating characteristic,ROC)曲线评价模型效能,用曲线下面积(area under the curve,AUC)、灵敏度、特异度、准确度表示。结果:T_(2)WI模型训练集AUC为0.94,灵敏度、特异度、准确度为0.83、0.87、0.85,测试集AUC为0.88,灵敏度、特异度、准确度为0.77、0.94、0.83;DCE模型训练集AUC为0.63,灵敏度、特异度、准确度为0.85、0.26、0.61,测试集AUC为0.65,灵敏度、特异度、准确度为0.88、0.25、0.64。结论:基于T_(2)WI影像组学模型对LuminalA型、Luminal B(HER-2阴性)型乳腺癌分子分型的预测具有良好的效能,预测能力优于DCE影像组学模型。
文摘Study of marine noctilucence in marine is important to fishery, environmental monitoring and military affairs. A luminous bacterial strain D2 was isolated from the marine sediment samples collected near Donghai Island in Zhanjiang, China. The primary cultural and luminescent conditions of luminous bacterium D2 which was identified as Vibrio sp. were determined in liquid culture. The results showed that pH 7.0, 35 ℃, with 2.0 % NaCI, were the best growth conditions, and pH5 - 6, 20℃, OD600 0.08, with 3.0 % NaCI, were the optimal luminescent conditions.