Retrospective assessment of cyclin-dependent kinase 5 mRNA and protein expression and its association with patient survival in breast cancer

Cyclin-dependent kinase 5 (Cdk5) is an atypical member of the cyclin-dependent kinase family and functions as a serine/threonine kinase that can be activated by non-cyclin binding activators p35 or p39. Cdk5 expression and activity has been linked with the development and progression of cancer; however, its expression in breast cancer has not been fully described. Protein expression of Cdk5 was determined in a large cohort of early-stage invasive breast cancer tumours (n = 1110) with long-term follow-up data using immunohistochemistry. Expression of CDK5 mRNA was assessed in the METABRIC cohort (n = 1980). Low nuclear and cytoplasmic expression of Cdk5 expression was significantly associated with shorter breast cancer-specific survival (P = .004 and P = .001, respectively). Importantly, low nuclear and cytoplasmic expression of Cdk5 remained associated with survival in multivariate analysis, including potentially confounding factors (hazard ratio (HR) = 0.612, 95% confidence interval (CI) = 0.418-0.896, P = .011 and HR = 0.507, 95% CI = 0.318-0.809, P = .004, respectively). In addition, low nuclear and cytoplasmic expression of Cdk5 was significantly associated with clinicopathological criteria associated with adverse patient prognosis. Low CDK5 mRNA expression was associated with shorter patient survival (P = .005) in the METABRIC cohort; no associations between copy gain or loss and survival were observed. These data suggest that low Cdk5 expression is associated with poor clinical outcome of breast cancer patients and may be of clinical relevance.     

鼻咽癌放疗后致迟发性放射性脑病34例临床分析

目的：探讨鼻咽癌放疗后致迟发性放射性脑病的临床特征。方法：对中南大学湘雅医院神经内科所收治的34例鼻咽癌放疗后致迟发性放射性脑病患者临床资料、治疗方法及预后进行回顾性研究。结果：34例迟发性放射性脑病患者的临床特征包括头痛、头晕、记忆力下降、精神异常、抽搐、复视、面瘫或面部麻木、听力下降、言语增多、肢体无力、走路不稳、肢端麻木等。头部MRIT1WI呈低信号,T2WI呈高信号,增强后呈不规则强化。34例均随访,其中死亡11例,占32.35%;现存活23例,17例伴有严重症状,生存质量差,占50%。结论：鼻咽癌放疗后致迟发性放射性脑病临床表现各异,患者预后较差,临床上需尽早诊断,积极治疗,定期随诊。     

Timing of surgery during the menstrual cycle and prognosis of breast cancer

There are conflicting reports on the differential effect of surgery performed during the two phases of the menstrual cycle, namely, follicular and luteal, and prognosis of operable breast cancer. A statistical meta-analysis of the published evidence suggests a modest survival benefit of 15+/-4% when the operation is performed during the luteal phase. Further research in this area might provide a novel avenue to understand the natural history of breast cancer. A spin off from these studies might be the understanding of the importance of events that occur at the time of surgery in determining long term prognosis.     

Prognostic relevance of miR-137 and its liver microenvironment regulatory target gene AFM in hepatocellular carcinoma

MiR-137 has been identified as potential hepatocellular carcinoma (HCC) prognostic biomarkers. Highly relevant HCC prognostic biomarkers may be derived from combinations of miR-137 with its target genes involved in the regulation of liver microenvironment. This study aimed at the discovery of such a combination with improved HCC prognosis performance than miR-137 or its target gene alone in a significantly higher number of HCC patients than previous studies. Analysis of the differentially expressed micro RNAs (miRNAs) between cancer and noncancer tissues reconfirmed miR-137 to be among the most relevant prognostic miRNAs and the data of 375 HCC patients and 50 normal cases were from the Cancer Genome Atlas (TCGA) data sets. Target genes were identified by the established search methods and Kaplan–Meier survival analysis of HCC patients was used to evaluate the overall survival (OS) and recurrence-free survival (RFS). Cox proportional hazards regression indicated that the miR-137 and its target gene AFM combination is an independent prognostic factor for the OS and RFS in HCC. In vitro experiments validated that miR-137 could bind to 3′-untranslated region of the AFM and promote the invasion and metastasis of HCC cell lines. The expressions of miR-137 and its liver microenvironment regulatory target gene AFM in combination significantly correlated with HCC progression in a higher number of patients than in previous studies, which suggested their potential as prognostic biomarkers for HCC.     

Cigarette smoking might weaken the prognostic significance of cytochrome P450 2C19*2 polymorphism in acute myocardial infarction patients

Prognostic significance of cytochrome P450 2C19*2 polymorphism in acute myocardial infarction is still not well investigated. The aim of the study was to determine the relationship between the genetic polymorphism and the outcome of the acute myocardial infarction patients, and to further clarify the impact of smoking on such relationship. Six hundred acute myocardial infarction patients were enrolled. All of them provided blood samples and underwent clopidogrel treatment. The genetic polymorphism was determined by polymerase chain reaction–restriction fragment length polymorphism analysis, and the platelet function was assessed using conventional aggregometry. Of the included patients, 287 carried GG wild‐type genotypes, 225 carried GA genotypes and 88 carried AA genotypes. The platelet aggregation rate was significantly elevated in the AA genotype patients, mainly in the non‐smoking patients (P < 0.001) and the former‐smoking patients (P < 0.001). During 5‐year follow‐up period, after adjusted for multiple confounding factors, AA genotypes were associated with the increase in 5‐year mortalities in the non‐smoking patients [OR: 7.06, 95% confidence interval (CI): 2.16–11.49] and the former‐smoking patients (OR: 4.38, 95% CI: 1.05–9.40), but not in the current‐smoking patients (OR: 1.12, 95% CI: 0.60–2.31). In conclusion, the study suggested a potential role of P450 2C19*2 polymorphism as a prognostic indicator in acute myocardial infarction patients. We had also obtained some evidence that current smoking might weaken the prognostic significance of the genetic polymorphism in patients.     

Ets-1在非小细胞肺癌中的表达及其临床意义

原癌基因Ets-1,与肿瘤的发生、浸润转移、血管生成及预后密切相关.通过采用免疫组化SP法和RT-PCR技术检测非小细胞肺癌(non-small cell lung cancer,NSCLC)组织及癌旁正常组织中Ets-1的表达,并分析与临床病理特征及预后的关系.免疫组化结果显示Ets-1蛋白在NSCLC组织中的阳性率为67%(65/97),显著高于对应的癌旁正常组织0%(0/30)(P<0.001).Ets-1阳性率随着肿瘤T分期的增加、淋巴结转移和临床分期的增加而增加(P<0.05),而与性别、年龄、吸烟、组织学类型及分化程度等无关(P>0.05).RT-PCR结果显示Ets-1 mR-NA在20例癌组中和癌旁组中的相对表达强度分别为0.5570±0.0593和0.2965±0.0869(P<0.001).Kaplan-Meier生存曲线显示,Ets-1阳性组的生存时间显著低于阴性组(P<0.05).Cox多因素分析模型显示Ets-1不是NSCLC患者的独立影像因素(P>0.05).结果表明,Ets-1的表达在NSCLC的浸润和转移中扮演了重要的角色,并对NSCLC患者生存期有一定的影响.     

SOX2-induced upregulation of lncRNA LINC01561 promotes non-small-cell lung carcinoma progression by sponging miR-760 to modulate SHCBP1 expression

Long noncoding RNAs (lncRNAs) have been shown to have critical regulatory roles in tumorigenesis. lncRNA LINC01561 (LINC01561) is a newly identified tumor-related lncRNA and its dysregulation has been demonstrated in several tumors. However, whether LINC01561 is involved in the progression of non-small-cell lung carcinoma (NSCLC) and its underlying mechanisms remain unknown. In this study, we first provided evidence that LINC01561 expressions were distinctly upregulated in NSCLC tissues and cell lines. Combining with bioinformatics assays and mechanism experiments, our group demonstrated that LINC01561 was activated by SOX2 in NSCLC. Clinical research revealed that upregulation of LINC01561 was related to poorer clinicopathologic features and shorter survival time. Functionally, suppression of LINC01561 exhibited tumor-suppressive functions through impairing cell proliferation, migration, and invasion as well as inducing apoptosis. Moreover, we verified that LINC01561 could directly bind to miR-760, isolating miR-760 from its target gene SHC SH2 domain-binding protein 1 (SHCBP1). We also found that SHCBP1 was lowly expressed in NSCLC and served as a tumor promoter. A functional study indicated that LINC01561 regulated SHCBP1 expression by competitively binding to miR-760. In summary, our findings indicated that SOX2-induced overexpression of LINC01561 promoted the proliferation and metastasis by acting as a competing endogenous RNA to modulate SHCBP1 by sponging miR-760.     

Identification of immune-enhanced molecular subtype associated with BRCA1 mutations,immune checkpoints and clinical outcome in ovarian carcinoma

Ovarian carcinoma has the highest mortality among the malignant tumours in gynaecology, and new treatment strategies are urgently needed to improve the clinical status of ovarian carcinoma patients. The Cancer Genome Atlas (TCGA) cohort were performed to explore the immune function of the internal environment of tumours and its clinical correlation with ovarian carcinoma. Finally, four molecular subtypes were obtained based on the global immune-related genes. The correlation analysis and clinical characteristics showed that four subtypes were all significantly related to clinical stage; the immune scoring results indicated that most immune signatures were upregulated in C3 subtype, and the majority of tumour-infiltrating immune cells were upregulated in both C3 and C4 subtypes. Compared with other subtypes, C3 subtype had a higher BRCA1 mutation, higher expression of immune checkpoints, and optimal survival prognosis. These findings of the immunological microenvironment in tumours may provide new ideas for developing immunotherapeutic strategies for ovarian carcinoma.     

子宫内膜癌中的lncRNA-miRNA-mRNA ceRNA网络的整合分析

子宫内膜癌(uterine corpus endometrial carcinoma,UCEC)是危害女性健康的癌症之一,但其发生发展机制尚不完全清楚.基因的异常表达在细胞癌变过程中发挥着重要的作用.本研究利用生物信息学方法对UCEC中异常表达的基因进行网络调控分析,为UCEC的机制研究及预后治疗提供理论依据.首先,利...     

Early B-cell factors involve in the tumorigenesis and predict the overall survival of gastric cancer

Gastric cancer (GC) is a heavy health burden around the world, which is the fifth most frequent tumor and leads to the third most common cancer-related deaths. It is urgent to identify prognostic markers as the guideline for personalized treatment and follow-up. We accessed the prognostic value of Early B-cell factors (EBFs) in GC. A total of 415 GC tissues and 34 normal tissues from The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) cohort, 616 external patients from {"type":"entrez-geo","attrs":{"text":"GSE15459","term_id":"15459"}}GSE15459, {"type":"entrez-geo","attrs":{"text":"GSE22377","term_id":"22377"}}GSE22377, {"type":"entrez-geo","attrs":{"text":"GSE51105","term_id":"51105"}}GSE51105, {"type":"entrez-geo","attrs":{"text":"GSE62245","term_id":"62245"}}GSE62245 were enrolled for analysis. Univariate and multivariate Cox regression analyses were employed to evaluate the sole and integrative prognostic value of EBFs, respectively. Genetic alterations, DNA methylation of EBFs were also evaluated, as well as the involved signaling pathways. We revealed that increased EBFs associated with the poor prognosis of GC patients, the prognostic model was established in TCGA-STAD cohort, and validated in Gene Expression Omnibus (GEO) cohorts, with effectiveness in both HER2 positive and negative patients. DNA methylation was involved in the impact on prognosis. Cell cycle, immune-associated, and MAPK pathways were influenced by EBFs. Anti-CTLA4 immunotherapy is more suitable for EBFs determining high-risk groups, but not anti-PD-1/PD-L1 therapy. 5-Fluorouracil, methotrexate, vorinostat are suitable to inhibit the function of EBFs. Our new findings provide novel insight into the prediction of prognosis and clinical treatment of GC patients based on EBFs.