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.     

硫氧还蛋白还原酶1(TrxR1)在胃癌中的表达及对胃癌细胞生长的影响*

目的: 探讨胃癌组织硫氧还蛋白还原酶1(TrxR1)表达与生存时间的关系及其对胃癌细胞生长的影响。方法: 用Real-time PCR法检测76例胃癌组织及癌旁TrxR1 mRNA表达,并分析其与胃癌患者临床病理特征及预后的关系;随机选取3例胃癌组织及癌旁组织,采用免疫组化法、Western blot法检测TrxR1蛋白表达。采用Western blot法和Real-time PCR法检测胃癌细胞系及人胃粘膜上皮细胞中TrxR1的表达。采用小RNA干扰序列(siRNA)处理AGS细胞,根据处理方法不同将AGS细胞分为3组:阴性对照组:转染NC-siRNA、TRXR1 siRNA干扰1组:转染TRXR1-siRNA1、TRXR1 siRNA干扰2组:转染TRXR1-siRNA2。使用Real-time PCR法检测各组AGS细胞中TrxR1 mRNA的表达,克隆形成试验和MTT法检测AGS细胞生长情况。结果: 胃癌组织中TrxR1 mRNA和蛋白表达量均显著性上调,TrxR1主要定位于细胞质中。TrxR1高表达与患者TNM分期及淋巴结转移有关,且TrxR1高表达组患者的中位生存时间短于低表达组(P＜0.05)。胃癌细胞中TrxR1表达量高于人胃粘膜上皮细胞系中的表达。TRXR1-siRNA1组AGS细胞和TRXR1-siRNA2组AGS细胞中TrxR1 mRNA和蛋白与NC-siRNA组相比均显著性降低(P＜0.05),且AGS细胞克隆形成与增殖能力均降低(P＜0.05)。结论: 胃癌组织中TrxR1高表达提示患者预后不良,沉默TrxR1能抑制胃癌细胞的增殖。     

Down-regulation of RBP4 indicates a poor prognosis and correlates with immune cell infiltration in hepatocellular carcinoma

Recent research has indicated that metabolically related genes play crucial roles in the pathogenesis of hepatocellular carcinoma (HCC). We evaluated the associations between novel biomarkers and retinol-binding protein 4 (RBP4) for predicting clinical HCC outcomes, hub-related genes, pathway regulation, and immune cells infiltration. Bioinformatic analyses based on data from The Cancer Genome Atlas were performed using online analysis tools. RBP4 expression was low in HCC and was also down-regulated in pan-cancers compared with normal tissues. RBP4 expression was also significantly different based on age (41–60 years old versus 61–80 years old), and low RBP4 expression levels were associated with advanced tumor stages and grades. Higher RBP4 expression was associated with better overall survival time in HCC patients, and we identified a deletion-mutation rate of 1.4% in RBP4. We also identified ten co-expressed genes most related to RBP4 and explored the relationships between six hub genes (APOB, FGA, FGG, SERPINC1, APOA1, and F2) involved in RBP4 regulation. A pathway enrichment analysis for RBP4 indicated complement and coagulation cascades, metabolic pathways, antibiotic biosynthesis pathways, peroxisome proliferator-activated receptor signaling pathways, and pyruvate metabolism pathways. These results suggest that RBP4 may be a novel biomarker for HCC prognosis, and an indicator of low immune response to the disease.     

LncRNA AWPPH as a prognostic predictor in human cancers in Chinese population: evidence from meta-analysis

Background: Long non-coding RNA associated with poor prognosis of hepatocellular carcinoma (AWPPH) is dysregulated in a variety of human cancers. However, the prognostic value of AWPPH in various cancers remains unclear.Methods: Comprehensive literature search was performed in PubMed, Web of Science, CNKI and Wangfang databases, and eligible studies were obtained according to the inclusion and exclusion criteria. The pooled hazard ratios (HRs) and odds ratios (ORs) were applied to assess the clinical value of AWPPH expression for overall survival (OS) and clinicopathological features.Results: A total of 19 articles including 1699 cancer patients were included in the study. The pooled results demonstrated that evaluated AWPPH expression was positively related to a poorer overall survival of patients with cancers (HR = 1.79, 95%CI: 1.44–2.14, P<0.001). Subgroup analysis revealed that tumor type and sample size affect the predictive value of AWPPH on OS, whereas cut-off value and HR estimation method have no impact on it. In addition, the pooled data also showed that AWPPH was positively linked to advanced TNM stage (OR = 2.50, 95%CI: 1.94–3.22, P<0.001), bigger tumor size (OR = 2.64, 95%CI: 1.47–4.73, P=0.001), macro-vascular invasion (OR = 2.08, 95%CI: 1.04–4.16, P=0.04) and lymph node metastasis (OR = 2.68, 95%CI: 1.82–3.96, P<0.001). Moreover, the results of the trim and fill analysis confirmed the reliability of our finding.Conclusions: Up-regulation of AWPPH was associated with advanced TNM stage, bigger tumor size, worse lymph node metastasis, macro-vascular invasion and shorter overall survival, suggesting that AWPPH may serve as a biomarker for prognosis and clinicopathological characteristics in human cancers among the Chinese population.     

新辅助化疗后腋窝病理完全缓解乳腺癌的预后分析

摘要 目的：研究乳腺癌患者新辅助化疗（NAC）后达到腋窝淋巴结病理完全缓解（pathologic complete response of axillary,apCR）的远期生存以及影响远期生存的相关因素分析。方法：回顾性分析哈尔滨医科大学附属肿瘤医院乳腺外科624例乳腺癌患者的住院资料,采用Kaplan-Meier生存分析以及COX回归分析的统计学分析方法,分析乳腺癌患者新辅助化疗后腋窝状态与无病生存（DFS）和总生存（OS）的关系及影响apCR预后的因素。结果：apCR与非apCR患者比较DFS（P=0.013）和OS（P=0.037）差异具有统计学意义,apCR患者的预后与年龄、肿瘤大小、肿瘤受体状态、HER-2、ki67状态、分子分型等因素无相关性。结论：与非apCR患者相比,乳腺癌患者新辅助化疗后apCR患者预后更好,但apCR患者预后良好的因素仍需进一步临床试验分析。     

NEDD9 overexpression: Prognostic and guidance value in acute myeloid leukaemia

It has been demonstrated that neural precursor cell expressed developmentally downregulated protein (NEDD) plays crucial roles in tumorigenesis and may serve as potential biomarkers in cancer diagnosis and prognosis. However, few studies systematically investigated the expression of NEDD family members in acute myeloid leukaemia (AML). We systemically determined the expression of NEDD family members in AML and determined their clinical significance. We identified that NEDD9 expression was the only member among NEDD family which was significantly increased in AML. NEDD9 overexpression was more frequently classified as FAB-M4/M5 (p = 0.008 and 0.013, respectively), hardly as FAB-M2/M3. Moreover, NEDD9 overexpression was significantly associated with complex karyotype and TP53 mutation. The significant association between NEDD9 overexpression and survival was also observed in whole-cohort AML and non-M3 AML patients. Notably, AML patients with NEDD9 overexpression may benefit from hematopoietic stem cell transplantation (HSCT), whereas those cases without NEDD9 overexpression did not. Finally, a total of 822 mRNAs and 31 microRNAs were found to be differentially expressed between two groups. Among the microRNAs, miR-381 was also identified as a microRNA that could direct target NEDD9. Taken together, our findings demonstrated that NEDD9 overexpression is associated with genetic abnormalities as well as prognosis and might act as a potential biomarker guiding the choice between HSCT and chemotherapy in patients with AML after achieving complete remission.     

Development and validation of glycolysis-related prognostic score for prediction of prognosis and chemosensitivity of pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with aggressive biological behaviour. Its rapid proliferation and tumour growth require reprogramming of glucose metabolism or the Warburg effect. However, the association between glycolysis-related genes with clinical features and prognosis of PDAC is still unknown. Here, we used the meta-analysis to correlate the hazard ratios (HR) of 106 glycolysis genes from MSigDB by the cox proportional hazards regression analysis in 6 clinical data sets of PDAC patients to form a training cohort, and a single group of PDAC patients from the TCGA, ICGC, Arrayexpress and GEO databases to form the validation cohort. Then, a glycolysis-related prognosis (GRP) score based on 29 glycolysis prognostic genes was established in 757 PDAC patients from the training composite cohort and validated in 267 ICGC-CA validation cohort (all P < .05). In addition, including PADC, the prognostic value was also confirmed in other 7 out of 30 pan-cancer cohorts. The GRP score was significantly related to specific metabolism pathways, immune genes and immune cells in the patients with PADC (all P < .05). Finally, by combining with immune cells, the GRP score also well-predicted the chemosensitivity of patients with PADC in the TCGA cohort (AUC = 0.709). In conclusion, this study developed a GRP score for patients with PDAC in predicting prognosis and chemosensitivity for PDAC.     

Serum interleukin-17 as a diagnostic and prognostic marker for non-small cell lung cancer

Abstract

Objective: The aim of this study was to explore the clinical role of serum interleukin (IL)-17 in patients with non-small-cell lung cancer (NSCLC).

Materials and method: Serum specimens from 128 patients with NSCLC and 60 healthy controls were collected. The concentrations of IL-17 were measured using enzyme-linked immunosorbent assay.

Results: Serum IL-17 levels were higher in the NSCLC group in comparison with the control group (p?<?0.01). With a cut-off value of 16?pg/ml, IL-17 showed a good diagnostic performance for NSCLC. Multivariate survival analysis indicated that IL-17 was an independent prognostic factor in NSCLC.

Conclusion: Measurement of IL-17 might be a useful diagnostic and prognostic value for patients with NSCLC.     

Genotyping of IL-8-251 T > A yields prognostic information in patients with gastric carcinoma

Abstract

This study was designed to investigate the association of the IL-8-251?T?>?A gene polymorphism with clinicopathological features and the prognostic role of the gene polymorphism in patients with gastric adenocarcinoma. The gene polymorphism was detected by the polymerase chain reaction–restriction fragment length polymorphism method, followed by univariate and multivariate analyses to elicit its prognostic role. The frequency of IL-8-251?A/A, A/T and T/T genotypes were 11.0% (23/210), 43.8% (92/210) and 45.2% (95/210), respectively. The IL-8-251 gene polymorphism was closely correlated with depth of invasion (p?=?0.007), grade of differentiation (p?=?0.002) and TNM stage (p?=?0.009). A/A genotype carriers showed more frequency of serosa involvement, low grade of differentiation and advanced stage of gastric carcinoma. IL-8-251?T?>?A gene polymorphism have no significant correlation with other clinicopathological features. The 5-year overall survival of IL-8-251?A/A genotype and T allele carriers were 30.8% and 59.2%, respectively. There is a significant discrepancy among the different genotype carriers. Multivariate analysis with the Cox regression model revealed that the IL-8-251?A/A genotype is an independent prognostic indicator (HR?=?2.285, 95% Confidence Interval?=?1.06–4.93, p?=?0.035). We conclude that the IL-8-251?A/A genotype may indicate a poor prognosis for gastric adenocarcinoma patients.