Dysregulated expression of circular RNAs serve as diagnostic and prognostic markers in ovarian and cervical cancer: A PRISMA-compliant systematic review and meta-analysis

Introduction:Recent studies have reported a connection between non-coding RNAs such as circular RNAs (circRNAs) and the prognosis of various cancers. However, the mechanism of circRNA in ovarian cancer and cervical cancer has not been consistent. We evaluated the diagnostic and prognostic roles of circRNAs in ovarian and cervical cancer by meta-analysis.Methods:Pooled hazard ratios with 95% confidence intervals were to estimate overall survival. Diagnostic efficacy was estimated by sensitivity, specificity and area under curve.Results:By searching PubMed, Embase, the Web of Science databases, and other sources, we obtained a total of 22 studies with 2059 patients from Asia population. High expression levels of oncogenic circRNAs were significantly associated with poor prognoses both in ovarian and cervical cancer. However, elevated expression levels of tumor-suppressor circRNAs were linked with favorable survival time in ovarian cancer. As for diagnostic role, the area under the curve value in ovarian cancer and cervical cancer is 0.89 and 0.93, respectively.Conclusions:CircRNAs have the prospect of becoming a promising biomarker for diagnosis and prognosis of ovarian and cervical cancer. Accordingly, circRNAs might be novel indicators and targets of therapy for ovarian and cervical cancer.     

Clinicopathological and prognostic significance of circRNAs in lung cancer: A systematic review and meta-analysis

Background:Circular RNAs (circRNAs) regulate multiple pathways during lung cancer pathogenesis. Apart from functional significance, many circRNAs have been shown to be associated with clinicopathological characteristics and predict lung cancer prognosis. Our aim is to summarize the expanding knowledge of clinical roles of circRNAs in lung cancer.Methods:A thorough search of literature was conducted to identify articles about the correlation between circRNA expression and its prognostic and clinicopathological values. Biological mechanisms were summarized.Results:This study included 35 original articles and 32 circRNAs with prognostic roles for lung cancer. Increased expression of 25 circRNAs and decreased expression of 7 circRNAs predicted poor prognosis. For non-small cell lung cancer, changes of circRNAs were correlated with tumor size, lymph node metastasis, distant metastasis, tumor node metastasis (TNM) stage, and differentiation, indicating the major function of circRNAs is to promote lung cancer invasion and migration. Particularly, meta-analysis of ciRS-7, hsa_circ_0020123, hsa_circ_0067934 showed increase of the 3 circRNAs was associated with positive lymph node metastasis. Increase of ciRS-7 and hsa_circ_0067934 was also related with advanced TNM stage. The biological effects depend on the general function of circRNA as microRNA sponge.Conclusions:CircRNAs have the potential to function as prognostic markers and are associated with lung cancer progression and metastasis.     

Identification of Key circRNAs in Non-Small Cell Lung Cancer

BackgroundOur work aimed to identify the key differentially expressed circular RNAs (circRNAs) (DECs) in non-small cell lung cancer (NSCLC).Materials and MethodsAn integrated analysis based on public NSCLC datasets obtained from Gene Expression Omnibus was performed. DECs in NSCLC were subsequently identified. Bioinformatics analyses were utilized for describing the predictable functions of DECs including circRNA-miRNA network construction and pathway enrichment. The diagnostic value of candidate DECs among NSCLC and healthy individuals were preliminarily evaluated in GSE101586, GSEE101684, GSE112214 datasets.ResultsA total of 43 up-regulated and 78 down-regulated DECs in NSCLC were identified. The mTOR signaling pathway, ErbB signaling pathway and cell cycle were significantly enriched from the originated genes of DECs in NSCLC. In the circRNA-miRNA network, hsa-circ-0002702, hsa-circ-0049271, hsa-circ-0009150 and hsa-circ-0053958 had high connectivity with miRNAs, which respectively interacted with 122, 42, 41, and 39 miRNAs. hsa_circ_0003028, hsa_circ_0015278, hsa_circ_0043256, hsa_circ_0049657 and hsa_circ_0074930 could distinguish NSCLC patients from healthy individuals in GSE101586, GSEE101684, GSE112214 datasets.ConclusionsDECs including hsa_circ_0003028, hsa_circ_0015278, hsa_circ_0043256, hsa_circ_0049657 and hsa_circ_0074930 had diagnostic value in NSCLC. These DECs might play key roles in NSCLC pathogenesis through the mTOR signaling pathway, ErbB signaling pathway and cell cycle.     

非小细胞肺癌中IGF1、IGFBP2表达与预后的相关性分析

目的探讨非小细胞肺癌组织胰岛素样生长因子1(IGF1)、胰岛素样生长因子结合蛋白2(IGFBP2),蛋白表达与患者临床病理特征及预后的关系。方法将226例确诊的非小细胞肺癌患者癌组织为非小细胞肺癌组;选取其癌旁正常组织为癌旁对照组。检测癌组织及癌旁正常组织IGF1、IGFBP2蛋白表达水平;分析非小细胞肺癌患者癌组织IGF1与IGFBP2蛋白表达相关性及其与预后的关系;并分析影响非小细胞肺癌患者预后的因素。结果非小细胞肺癌组IGF1、IGFBP2蛋白高表达率高于癌旁对照组(P<0.05)。非小细胞肺癌患者癌组织IGF1、IGFBP2蛋白表达与肿瘤大小、淋巴结转移、组织分化程度、TNM分期有关(P<0.05)。非小细胞肺癌患者癌组织IGF1与IGFBP2蛋白表达呈正相关(r=0.472,P<0.05)。IGF1、IGFBP2高表达患者五年生存率(33.33%、29.41%)低于低表达患者(69.23%、73.33%)(P均<0.05)。IGF1高表达、IGFBP2高表达、TNMⅢ～Ⅳ期是影响非小细胞肺癌患者死亡的独立危险因素(P<0.05)。结论 IGF1、...     

长链非编码RNA EXOC7在非小细胞肺癌中的表达及临床意义分析

目的分析长链非编码RNA(lncRNA)EXOC7在非小细胞肺癌中的表达及临床意义。方法本研究纳入2015年1月~2018年5月收治的75例非小细胞肺癌患者,采用实时定量反转录聚合酶链反应(qRT-PCR)方法检测lncRNA EXOC7在非小细胞肺癌组织及对应癌旁组织中的表达,比较癌及癌旁组织中lncRNA EXOC7的表达差异性,并分析癌组织中lncRNA EXOC7的表达与患者临床病理特征及预后的关系。结果非小细胞肺癌组织中lncRNA EXOC7的相对表达水平(7.88±1.04)明显高于癌旁组织(1.33±0.79),差异具有统计学意义(P<0.001)。不同性别、年龄、病理类型、组织分化程度的非小细胞肺癌患者组织中lncRNA EXOC7的表达无明显差异性(P>0.05),但不同TNM分期、淋巴结转移状况与非小细胞肺癌患者组织中lncRNA EXOC7的表达存在显著差异性(P<0.05)。lncRNA EXOC7高表达组无进展生存期[(10.09±1.93)个月]明显短于低表达组[(19.77±2.16)个月],差异有统计学意义(P<0.05)。lncRNA EXOC7高表达组总生存期[(14.82±2.05)个月]明显短于低表达组[(26.18±2.87)个月],差异有统计学意义(P<0.05)。结论lncRNA EXOC7在非小细胞肺癌组织中表达上调,其可能作为一种促癌因子参与非小细胞肺癌的发生及发展过程,并与患者的不良预后有关。     

RNA-sequencing of peripheral blood circular RNAs in Parkinson disease

Background:Circular RNAs (circRNAs) play an important role in many neurological diseases and can serve as biomarkers for these diseases. However, the information about circRNAs in Parkinson disease (PD) remained limited. In this study, we aimed to determine the circRNAs expression profile in PD patients and discuss the significance of circRNAs in the diagnosis of PD.Methods and Results:Using RNA-sequencing in peripheral blood RNAs, we showed that a significant number of mRNAs or circRNAs were differentially expressed between PD patients and normal controls (NCs), which included 273 up-regulated and 493 down-regulated mRNAs, and 129 up-regulated and 282 down-regulated circRNAs, respectively. Functional analysis was performed using the Kyoto Encyclopedia of Gene and Genomes (KEGG) pathway analysis, and the results showed that the second most enriched KEGG pathway was PD. These data suggest that the levels of mRNAs and circRNAs in peripheral blood could be potentially used as biomarkers for PD. In addition, we correlated mRNAs and circRNAs by constructing a competing endogenous RNA (ceRNA) network in PD. The resulted-in ceRNA network included 10 differentially expressed mRNAs from PD pathway, 13 predicted miRNAs, and 10 differentially expressed circRNAs.Conclusion:Collectively, we first characterized the expression profiles of circRNAs and mRNAs in peripheral blood from PD patients and proposed their possible characters in the pathogenesis of PD. These results provided valuable insights into the clues underlying the pathogenesis of PD.     

Elevated expression of USP9X correlates with poor prognosis in human non-small cell lung cancer

Background

The aim of this study was to investigate the expression of ubiquitin-specific peptidase 9, X-linked (USP9X) in non-small cell lung cancer (NSCLC) patients and to evaluate the relevance of USP9X expression to tumor prognosis.

Methods

Ninety-five patients who underwent surgical resection for clinical stage I-IIIA NSCLC between July 2008 and July 2011 were included in this study. Immunohistochemical analysis of USP9X expression was performed on 95 NSCLC tissues and 32 adjacent normal lung parenchymal tissues from these patients. The Chi-squared test was used to compare the clinicopathological characteristics between different groups. Kaplan-Meier analysis and a Cox regression model were used to determine the independent prognostic factors. A P value <0.05 was considered to be significant.

Results

The expression of USP9X was found to be significantly higher in NSCLC tissue (44.2%) than in adjacent normal lung parenchymal tissue (6.3%) (P<0.001). High USP9X expression was significantly associated with positive lymph node metastasis (P<0.001), clinical stage (P<0.001) and a reduced overall survival rate (P=0.001) in patients with NSCLC. Based on the multivariate analysis, the elevated expression of the USP9X protein was a significant predictor of poor prognosis for NSCLC patients (HR =2.244, P=0.028).

Conclusions

The current study demonstrated that the expression of USP9X in NSCLC tissue was significantly higher than that in normal lung tissue and that this elevated expression level of USP9X was associated with poor prognosis among NSCLC patients, suggesting that USP9X might serve as a prognostic biomarker for NSCLC.     

Cytoplasmic expression of G protein-coupled estrogen receptor 1 correlates with poor postoperative prognosis in non-small cell lung cancer

BackgroundA hormonal role in the development of non-small cell lung cancer (NSCLC) has been well documented, and the classic estrogen receptors (ERs)—ERα and ERβ have been extensively investigated over the past decade. The expression of ERβ was found to be high and display biological activity in NSCLC, but anti-estrogen therapy targeting this receptor has shown limited efficacy for the disease. The third estrogen receptor, G protein-coupled estrogen receptor 1 (GPER1/GPR30), was recently found to be highly expressed in NSCLC. Herein, we aimed to investigate the expression profile of GPER1 and correlate it with clinicopathological factors as well as postoperative prognosis in NSCLC.MethodsWe examined GPER1 and ERβ expression using immunohistochemistry among 183 NSCLC cases, including 132 lung adenocarcinoma (LUAD) with identified epidermal growth factor receptor (EGFR) mutation status and 51 squamous cell carcinoma (SCC) patients. We then conducted correlation analysis between the expression of GPER1 and clinicopathological factors and patients’ postoperative prognosis.ResultsPositive expression of GPER1 was categorized into 2 main classes: nuclei-GPER1 (nGPER1) and concurrent nuclei-and cytoplasm-GPER1 (n/cGPER1), according to its subcellular localization. The LUAD with wild-type EGFR (wt-EGFR) had a higher frequency of n/cGPER1 (50%) but a lower frequency of nGPER1 (31%) when compared with those with mutated EGFR (n/cGPER1: 31%, nGPER1: 41%, respectively). The expression of GPER1, regardless of subcellular localization, was positively correlated with tumor stage and lymph node metastasis. The median recurrence-free survival (mRFS) and overall survival (OS) were significantly worse in participants with n/cGPER1 expression than in those with nGPER1 or without GPER1 expression.ConclusionsThis study revealed that GPER1 is aberrantly highly expressed and presents a unique GPER1 expression profile in NSCLC. The n/cGPER1 expression was significantly associated with EGFR mutation status, tumor stage, lymph node metastasis, and poor postoperative prognosis in NSCLC.     

EFhd1蛋白在非小细胞肺癌组织中的表达及临床意义

目的探讨EFhd1蛋白在非小细胞肺癌(NSCLC)组织中的表达及临床意义。 方法收集南通大学附属医院心胸外科2004年1月至2011年4月收治的178例NSCLC手术患者的病例及其相应的临床病理和随访资料,并制备组织芯片;采用免疫组化方法检测EFhd1蛋白的表达,统计分析EFhd1蛋白与NSCLC患者临床病理参数、预后之间的相关性。 结果EFhd1在NSCLC组织(43.3%,77/178)中的表达明显高于癌旁组织(2.0%,1/51),差异有统计学意义(P<0.05)。统计分析显示：EFhd1的表达与T分期有关(P<0.05);Cox单因素分析显示,患者的TNM分期、T分期、N分期与NSCLC的预后密切相关(P<0.01);多因素分析显示EFhd1的高表达以及TNM分期为NSCLC的独立预后因素(P<0.05)。生存曲线提示EFhd1高表达的患者较EFhd1低表达患者生存期短,预后差,TNM分期越晚则生存时间越短。 结论EFhd1在NSCLC癌组织中的表达较癌旁组织中明显增高;TNM分期和EFhd1蛋白表达程度是影响患者预后的独立危险因素;EFhd1基因的高表达与患者的不良预后密切相关;EFhd1可作为NSCLC诊断及判断预后的潜在分子标记物,为后续研究其作为NSCLC靶向治疗的基因靶点的可能性提供了理论基础。     

非小细胞肺癌细胞凋亡与增殖的关系及其临床意义

目的 探讨非小细胞肺癌(NSCLC)细胞凋亡与增殖的关系及其临床病理意义。方法 采用SABC免疫组化法检测43例NSCLC及20例癌旁正常肺组织石蜡包埋标本增殖细胞核抗原(PCNA)表达；以PCNA标记增殖指数，检测其增殖活性；用TUNEL法检测细胞凋亡的情况，并分别定义凋亡指数(AI)和增殖指数(MI)。结果 ①NSCLC组织细胞AI、MI均明显高于癌旁正常肺组织；②癌旁正常肺组织、NSCLC组织增殖／凋亡比值分别为11．97和10．956，二者无显著差异。③细胞凋亡与肺癌的组织类型、临床分期及淋巴结转移无关，而与患者的预后及组织分化程度相关；细胞增殖与肺癌的组织类型、组织分化程度及淋巴结转移无关，而与患者的预后、临床分期密切相关。结论 NSCLC患者的AI、MI明显增高，可以作为肺癌预后及早期诊断的参考指标。     

CDKN2A基因在非小细胞肺癌中表达及生物学功能生物信息分析

目的探讨细胞周期蛋白依赖激酶抑制剂2A(CDKN2A)在人非小细胞肺癌(NSCLC)中表达、生物学功能和患者预后的关系。方法应用生物信息分析技术探讨癌症基因组图谱数据库(TCGA)中CDKN2A在NSCLC患者肿瘤组织和正常肺组织中的表达情况。采用蛋白-蛋白相互作用(PPI)数据库STRING分析CDKN2A编码蛋白作用网络,并进行聚类分析。采用基因本体论(Gene Ontology,GO)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEEG)富集CDKN2A和相关蛋白的生物学功能和信号通路。同时分析CDKN2A高低表达与NSCLC患者的无疾病进展生存和总生存的关系。同时采用免疫组化检测62例NSCLC患者癌组织和癌旁组织中CDKN2A表达情况分析CDKN2A阳性和阴性表达组患者生存期是否存在差异。结果CDKN2A基因在多种实体肿瘤包括乳腺癌、食管癌、肠癌等中表达水平明显上调。在NSCLC患者癌组织中CDKN2A表达水平明显高于正常肺组织(P<0.05)。而CDKN2A表达水平与肿瘤分期无明显相关性(P>0.05)。CDKN2A相关蛋白PPI网络中,相互作用关系指数为24.8,区域聚类指数为0.74,相互作用蛋白呈现明显的聚类表达(P<0.05)。CDKN2A编码蛋白主要定位在细胞核、细胞膜和囊泡;分子功能主要为蛋白结合、核蛋白结合和铁结合。而生物学过程主要集中于代谢、细胞增殖及对刺激的反应。KEGG信号通路主要为细胞周期调控、DNA蛋白结合以及Wnt信号通路。CDKN2A高表达NSCLC患者总生存期明显低于低表达组,且差异有统计学意义(HR=1.3,P=0.02),而CDKN2A高低表达组间NSCLC患者无疾病进展生存无统计学差异(HR=0.94,P=0.59)。62例NSCLC患者癌组织中CDKN2A阳性表达11例(17.7)而对应癌旁组织中阳性表达49例(79.0%),癌组织中CDKN2A阳性标的率显著高于癌旁组织(P<0.05)。而CDKN2A阳性组与阴性组患者生存期差异无统计学意义(HR=0.99,P>0.05)。结论CDKN2A在NSCLC患者癌组织中表达升高,并与患者预后不良有关,有望成为NSCLC预后和治疗的靶点。     

Integrated analysis of circRNAs and mRNAs expression profile revealed the involvement of hsa_circ_0007919 in the pathogenesis of ulcerative colitis

Background

Ulcerative colitis (UC) is characterized by chronic inflammation in the colon and epigenetic factors underlying the occurrence. Circular RNAs (circRNAs) have been under intensive focus due to the circular construct and gene-regulating functions. However, the changes and roles of circRNAs in UC remain unknown.

Methods

Microarrays were used to detect the differentially expressed genes, and quantitative real-time PCR was used to identify the changes in UC. In silico analyses were performed to predict the functions of circRNAs and mRNAs. In vitro, epithelial cell lines were stimulated by pro-inflammation effectors to test the alterations in circRNAs. CircRNAs–microRNAs–mRNAs network clarified the potential mechanisms underlying circRNAs in UC. The binding site between hsa_circ_0007919 and miR-138 or let-7a was verified using dual-luciferase assay.

Results

A total of 264 significantly dysregulated circRNAs and 1869 differentially expressed mRNAs in inflamed mucosa were compared with the non-inflamed mucosa in UC. Hsa_circ_0004662 and hsa_circ_0007919 were altered largely in UC tissues. Hsa_circ_0007919 was reduced persistently after inflammatory treatments, and it was relevant to Mayo endoscopic subscores and the expression of tight junction molecules. Finally, hsa_circ_0007919 could harbor miR-138, and let-7a to regulate the targeted mRNAs EPC1 and VIPR1.

Conclusions

Several circRNAs were differentially expressed in UC. Hsa_circ_0007919 is related to clinical characteristics and epithelial integrity by binding to hsa-let-7a, hsa-miR-138 to regulate the target genes. CircRNAs, especially hsa_circ_0007919, are associated with the pathogenesis and development of UC, with potential diagnostic and therapeutic implications.

     

miR-1290 is a potential prognostic biomarker in non-small cell lung cancer

Background

miR-1290 is a newly discovered microRNA (miRNA), and its role in non-small cell lung cancer (NSCLC) remains unknown. This study aimed to evaluate the expression levels of miR-1290 in NSCLC tissues and serum, and explore its associations with clinicopathological characteristics and prognosis of NSCLC patients.

Methods

A total of 33 pairs of tissues and 73 serum samples were obtained from NSCLC patients and expression levels of miR-1290 were detected by specific TaqMan qRT-PCR. The relationship between miR-1290 expression levels in NSCLC tissues and serum and clinicopathological characteristics was estimated respectively. The correlation between serum miR-1290 expression levels and overall survival of NSCLC patients was performed by Kaplan-Meier analysis and Cox proportional hazards model.

Results

We determined that miR-1290 expression levels were increased significantly in NSCLC tissues compared with non-tumor adjacent normal tissues, and higher miR-1290 expression levels were positively correlated with high tumor stage (P=0.004) and positive lymph node metastasis (P=0.013). Compared with benign lung disease and healthy controls, serum levels of NSCLC patients exhibited higher expression of miR-1290. Furthermore, the up-regulation of serum miR-1290 more frequently occurred in NSCLC patients with high TNM stage, positive lymph node metastasis (P=0.022 and P=0.024, respectively). Kaplan-Meier analysis demonstrated that high serum miR-1290 expression levels predicted poor survival (P=0.022). Cox proportional hazards risk analysis indicated that miR-1290 was an independent prognostic factor for NSCLC.

Conclusions

Our study suggests that miR-1290 is overexpressed in NSCLC, and serum miR-1290 may be used as a potential prognostic biomarker for NSCLC.     

Correlation of EGFR G873R mutation with prognosis of docetaxel in non-small cell lung cancer

BackgroundClinical features of epidermal growth factor receptor (EGFR) mutations have been commonly recognized in variant cancers. The role of EGFR mutations in non-small cell lung cancer (NSCLC) has spurred research and drug development efforts. However, there are still mutations that have not been widely reported, and their influences on NSCLC have not been fully elucidated; EGFR G873R mutation is just one of them. The aim of this study was to investigate the correlation between EGFR G873R mutation and the prognosis of chemotherapy in NSCLC.MethodsA total of 54 patients with NSCLC were enrolled in this study. Immunohistochemical staining was used to detect the expression of EGFR. A DNA extraction kit (GeneRead DNA FFPE Kit) was used to extract total DNA from resected cancer tissues. Genomic DNA targets were amplified by polymerase chain reaction (PCR), and then the amplicons were purified and sequenced. Statistical methods were performed to detect the relationship between EGFR G873R mutation and various clinicopathological features and the effect of EGFR G873R mutation on the prognosis of chemotherapy.ResultsEGFR G873R mutation did not show statistical significance, with EGFR high expression identified in 30 cases (P>0.05). Patients with EGFR G873R mutation had a significantly favorable prognosis of docetaxel (P=0.032), and for patients treated with docetaxel, EGFR G873R mutation was significantly correlated with better 5-year disease-free survival (DFS; P=0.026) and overall survival (OS; P=0.026). However, there was no statistical significance found between EGFR G873R mutation and the prognosis of vinorelbine (P>0.05), and for patients treated with vinorelbine, EGFR G873R mutation had no statistical significance with 5-year DFS (P>0.05) and OS (P>0.05).ConclusionsEGFR G873R mutation was remarkably correlated with the prognosis of docetaxel in NSCLC, which indicates that EGFR G873R may be employed as a promising biomarker to identify individuals with better prognosis of docetaxel and as an antitumor target for NSCLC treatment.     

Current research on circular RNAs associated with colorectal cancer

Representing a novel type of endogenous noncoding RNAs, circular RNAs (circRNAs) have recently gained much attention for their involvement in multiple biological processes. CircRNAs are ubiquitously expressed in eukaryotic cells and modulate gene expression by acting as sponges of microRNAs (miRNAs) or other proteins, such as RNA-binding proteins (RBPs). Due to their unique structure, circRNAs are more stable than linear RNAs. Expression profiles of circRNAs are associated with clinicopathological characteristics of colorectal cancer patients, such as differentiation, TNM classification and distant metastasis. Furthermore, circRNAs play crucial roles in multiple processes associated with malignant phenotypes, including cell proliferation/cycle, apoptosis and invasion. Improvements in RNA-sequencing methods have helped researchers to elucidate molecular interactions between circRNAs and colorectal cancer. This review provides a comprehensive overview of the features and functions of circRNAs, as well as insights into their roles in the onset and development of colorectal cancer. Combined with the reported results, the identification of circRNAs associated with colorectal cancer will certainly contribute to early detection and help to design treatment strategies for colorectal cancer. Screening for circRNAs may provide an accessible, noninvasive yet highly sensitive diagnosis for colorectal cancer. Furthermore, a better understanding of the roles of circRNAs may also provide a novel predictive feature in colorectal cancer therapy and prognosis.     

PTTG、VEGF-C 的表达及微淋巴管密度与非小细胞肺癌临床病理特征的关系

目的检测非小细胞肺癌（non-small cell lung cancer,NSCLC）、癌旁组织及肺良性病变组织中垂体瘤转化基因（pituitary tumortrans-forming gene,PTTG）及血管内皮生长因子-C（vascular endothelial growth factor,VEGF-C）的表达和微淋巴管密度（lymphatic microvessel density,LMVD）值,并探讨三者间的相互关系。方法应用实时荧光定量PCR和免疫组织化学方法检测非小细胞肺癌组织中PTTG、VEGF-C mRNA和蛋白及LM-VD的表达,分析PTTG、VEGF-C及LMVD与NSCLC临床病理特征的关系,以及PTTG、VEGF-C和LMVD三者之间的相互关系。同时,对随访资料进行生存分析,绘制生存率曲线,探讨PTTG、VEGF-C对肺癌患者预后的影响。结果PTTG、VEGF-C mRNA和LMVD值在不同性质的肺病变组织中的表达均有显著性差异（P均〈0.05）,在不同年龄、性别、是否吸烟、肿瘤大小、组织学类型及分化程度间无显著性差异（P均〉0.05）,在TNM分期、淋巴结转移与否及预后组间有显著性差异（P均〈0.05）。PTTG、VEGF-C蛋白表达在淋巴结转移与否及预后组间有显著性差异（P均〈0.05）。生存率曲线显示PTTG、VEGF-C高表达者生存时间均短于低/无表达者（P=0.030,0.027,n=65）。PTTG在肺癌组织中的表达与VEGF-C、LMVD密切相关,随着PTTG强度增加,VEGF-C分级及LMVD值亦增加。结论PTTG、VEGF-C的过度表达促使肿瘤微淋巴管的生成,进而促进了肿瘤细胞淋巴结转移。PTTG和VEGF-C表达可作为判断NSCLC生物学行为及肺癌患者预后的良好指标,VEGF-C有望成为肺癌抗淋巴管治疗的新靶点。     

Expression of hENTl and ERCC1 genes in tumor tissues non-small cell lung cancer

ObjectiveTo investigate the expression of hENTl and ERCC1 genes in tumor tissues non–small cell lung cancer (NSCLC).MethodsFresh non–small lung cancer specimens were transplanted into nude mice. Twenty mice were randomized into two groups: experimental group receiving gemcitabine plus cisplatin and control group receiving 0.9% physiological saline. The expressions of hENTl and ERCC1 mRNA in tumor tissue were detected by real–time fluorescent quantitative PCR. The volume of tumor, the weight of nude mice and tumor volume were respectively measured and calculated 2–3 times per week. Tissue samples were collected from NSCLC mice treated with gemcitabine plus carboplatin.ResultsThe histological examination showed that many tumor cells were well preserved in nude mice. The rate of transplanted tumor cells was 86.7%. The concomitant treatment study showed that the rate of TV, RTV, T/C in GEM + DDP group was the lowest. LBP + DOC, DDP + DOC obviously influenced the body weight. Compared with NS group, DDP group, GEM group, the survival period and the level of hENTl of DDP+GEM group increased obviously, the level of ERCC1 decreased significantly (P<0.05).ConclusionsThe expression of hENT1 and ERCC1 genes in tumor tissues were closely correlated with the response to chemotherapy and prognosis of patients with NSCLC treated with gemcitabine plus cisplatin.     

The profile analysis of circular RNAs in cervical cancer

Cervical cancer (CC) is the third most common cancer among women and has a high mortality rate at the advanced stage. The mechanisms underlying the development and progression of CC are still elusive. Circular RNAs (circRNAs) play an important role in various physiological and pathological processes. The aim of this study was to identify the circRNAs significantly associated with cervical squamous cell carcinoma (CSCC), in order to discover novel diagnostic markers and elucidate their mechanistic basis.The circRNA expression profiles of CSCC and paired para-cancerous cervical tissues was downloaded from the Gene Expression Omnibus. Bioinformatics analysis were used to screen for the differentially expressed circRNAs (DECRs). The expression levels of hsa_circ_0000745, hsa_circ_0084927, hsa_circ_0002762, hsa_circ_0075341, hsa_circ_0007905, hsa_circ_0031027, hsa_circ_0065898, hsa_circ_0070190, and hsa_circ_0078383 were verified in CC and normal cervical tissues by quantitative real-time PCR.A total of 197 DECRs were identified between the CSCC and normal tissues, including 87 upregulated and 110 downregulated circRNAs. In addition, 37 miRNAs were predicted for the upregulated circRNAs and 39 for the downregulated circRNAs. Functional analysis showed that the DECRs were associated with positive regulation of substrate adhesion-dependent cell spreading, metabolism, positive regulation of GTPase activity, protein regulation, and intercellular adhesion. The MAPK signaling pathway that plays a significant role in the progression of CC, was also enriched. Consistent with the in-silico analysis, hsa_circ_0000745, hsa_circ_0084927, hsa_circ_0002762, hsa_circ_0007905 were upregulated and hsa_circ_0078383 was downregulated in CC tissues (P < .001), whereas hsa_circ_0075341 (P < .001) and hsa_circ_0031027 (P = .001) showed opposite trends.We identified novel diagnostic and therapeutic biomarkers of CSCC along with the mechanistic basis.