长链非编码RNA ELFN1-AS1在子宫内膜癌中的表达及其临床意义

目的 基于生物信息学探讨长链非编码RNA(lncRNA) ELFN1-AS1在子宫内膜癌(UCEC)中的表达及其临床意义。方法 从癌症基因组图谱(TCGA)数据库下载552例UCEC组织样本和35例癌旁组织样本的转录组测序(RNA-seq)数据及相关临床资料,基于R语言进行相关生物信息学分析,以解析ELFN1-AS1在UCEC中的表达及其与临床病理特征、预后及免疫细胞浸润的相关性,并评估其在UCEC中的诊断价值。结果 ELFN1-AS1在UCEC组织中的表达呈升高趋势(P<0.001),其表达水平与肿瘤组织学分级、残瘤分级显著正相关(P均<0.05),且高表达患者的总生存期(OS)、疾病相关生存期(DSS)及无进展间隔期(PFI)均显著短于低表达患者(P<0.05),是影响UCEC患者OS的独立危险因素。肿瘤免疫细胞浸润分析显示,ELFN1-AS1与辅助性T细胞2(Th2)的浸润水平呈正相关,而与CD56^bright NK、中性粒细胞、嗜酸性粒细胞以及未成熟树突状细胞(iDC)的浸润呈负相关(|Spearman’s r|>0.15,P<...     

长链非编码RNA IGFBP4-1在鼻咽癌中的表达及临床意义

目的:探讨鼻咽癌(nasopharyngeal carcinoma,NPC)患者癌组织中长链非编码RNA IGFBP4-1(LncRNA IGFBP4-1)的表达及临床意义.方法:选取2014年1月至2014年12月海南省人民医院(海南医学院附属海南医院)耳鼻喉科收治的NPC患者88例为研究组,同期慢性鼻咽炎患者66例...     

肝细胞癌相关长链非编码RNA差异表达的研究

目的分析肝细胞癌与正常肝组织中差异表达的长链非编码RNA(lncRNA),发现可能与肝细胞癌发生发展相关的特异lncRNA。方法采用lncRNA表达谱芯片技术检测5例肝细胞癌和其配对癌旁正常组织中的lncRNA,筛选出差异表达的lncRNA。运用分层聚类分析,对所有的lncRNA进行分类。最后从中选择10个lncRNA用RT-PCR进行定量验证。结果有1359个lncRNA表达水平出现显著性差异,差异倍数〉2倍。其中629个显著上调,占46.2%,其中125个表达5倍以上;730个显著下调,占53.7%,其中110个表达5倍以上。聚类分析(1)基因间lncRNA有11706条,其中与已知编码基因相距300 kb的lncRNA共有352条。(2)增强子型lncRNA共有1802条,其中与已知编码基因相距300 kb的lncRNA共有42条。(3)HOX基因簇共有101条。RT-PCR结果有8条lncRNA表达趋势与基因芯片结果一致。对癌组和癌旁组进行检验,有6条差异有统计学意义(P0.05)。结论与癌旁组织比较,lncRNA肝细胞癌组织中的表达水平明显改变,可能与肝细胞癌的发生发展有关。     

长链非编码RNA及其在免疫系统中的研究

长链非编码RNA(lncRNA)一直被认为是“暗物质”而未受到人们的重视,直至2007年,斯坦福大学的研究者报道了同源异型基因转录反义RNA (HOTAIR)作为一种lncRNA可与蛋白复合体polycomb相互作用,并抑制同源异型基因(HOX)的转录,参与生物体生长发育的调节过程.自此之后,lncRNA受到了广泛的关注.lncRNA可以在表观遗传学水平、转录水平、转录后水平调节包括基因印迹、细胞定向分化、细胞增殖、细胞周期、肿瘤、神经退行性疾病、免疫细胞的发育与分化以及机体免疫反应的调节等多种病理生理过程.因而研究lncRNA的定义、分类及其发挥功能的机制具有重要意义.     

长链非编码RNA在结肠癌组织与癌旁组织中的表达研究

目的:筛选出结肠癌差异表达的长链非编码RNA(lncRNA),并分析其在结肠癌组织和相应癌旁组织中的差异表达情况。方法:从lncRNAtor数据库下载结肠癌组织中差异表达的lncRNA数据(Colon adenocarcinoma:Person neoplasm cancer status),包含36例结肠癌组织及29例正常结肠组织,以P0.01且差异表达倍数大于2或小于0.5的条件筛选出lncRNA,并用real-time PCR进一步验证其在60对结肠癌组织及癌旁组织中的表达情况。结果:分析结肠癌lncRNA数据发现,与正常组织相比,结肠癌组织共有50个lncRNA差异表达,其中28个高表达,22个低表达(P0.01)。筛选的4个lncRNA在60对结肠癌及癌旁组织标本中的验证结果为:HNF1AAS1和ZDHHC8P1的表达均上调(P0.01),SUZ12P表达下调(P0.05)。临床Ⅰ-Ⅱ期结肠癌组织中HNF1AAS1的表达水平明显低于Ⅲ-Ⅳ期(P0.05),ROC曲线分析显示,HNF1A-AS1、ZDHHC8P1和SUZ12P诊断结肠癌的ROC曲线下面积(AUC)分别为0.729(敏感性为78%,特异性为67%)、0.617(敏感性为68%,特异性为55%)和0.689(敏感性为65%,特异性为55%)。结论:长链非编码HNF1A-AS1和ZDHHC8P1在结直肠癌组织中表达上调,SUZ12P在结直肠癌组织中表达下调,其表达水平可能与结肠癌的发生存在关联。     

长链非编码RNA在卵巢癌中的研究进展

长链非编码RNA (lncRNA)是指长度超过200个核苷酸、具有调控基因表达作用的非编码RNA,近年来,因其具有复杂的生物学功能而引起了研究者的广泛关注.目前研究证实,lncRNA与多种肿瘤的发生发展有着密切的关系,可能参与促进或抑制肿瘤的生长和与肿瘤的转移有关.在卵巢癌中,某些lncRNA也被证实可能参与其致病过程.     

长链非编码RNA及其在下咽鳞状细胞癌发生发展中的作用机制

目的 总结长链非编码RNA(LncRNA)在肿瘤发生、发展中的调控机制,以及LncRNA在下咽鳞状细胞癌(HSCC)发生、发展中的作用。方法 在中国知网、万方数据、PubMed、谷歌学术、EMBASE等数据库上,以“长链非编码RNA,下咽癌/下咽鳞状细胞癌” “β-连环蛋白,下咽癌/下咽鳞状细胞癌”“ LncRNA, tumor ” “ LncRNA, Hypopharyngeal carcinoma/ HSCC ”“Wnt/β-catenin ,EMT”“Wnt/β-catenin or/and EMT,Hypopharyngeal carcinoma/HSCC”等为关键词,检索2000年1月—2018年5月国内外针对LncRNA及其在HSCC发生发展中作用机制进行研究的有关文献资料,共检索到文献3 297篇,最终纳入44篇文献,其中中文文献2篇、英文文献42篇。总结LncRNA对肿瘤调控机制的研究进展,并对 LncRNA和Wnt通路在HSCC发生发展中的作用机制进行重点分析。结果 LncRNA广泛参与DNA损伤修复和细胞凋亡等生理或病理过程,在生物调节过程中扮演着重要角色;Wnt信号通路是重要的细胞信号转导通路,在细胞的增殖、分化中发挥重要的作用。LncRNAs与mRNA结合促进了HSCC的发生发展,LncRNA通过Wnt信号通路促进HSCC的转移及复发。结论 LncRNA与许多肿瘤等多种疾病的发生密切相关;HSCC的发生发展受LncRNA的调控,LncRNA通过Wnt信号通路在HSCC肿瘤细胞的生长、迁移、侵袭中发挥重要作用。     

长链非编码RNA亚细胞定位和功能的研究进展

长链非编码RNA(lncRNA)的亚细胞定位和其功能息息相关,定位于细胞核时,lncRNA可以维持染色质结构,调控基因转录,参与mRNA的可变剪接;定位于细胞质时参与信号传导、转录后调控、翻译和翻译后修饰;定位于细胞器时协助完成细胞器的功能。lncRNA的亚细胞定位机制与其自身序列、结合蛋白等密切相关。此外通过构建核滞溜载体Snovector、添加胞质定位元件等强制改变lncRNA的亚细胞定位,以及利用APEX2等技术研究lncRNA亚细胞定位和其功能之间的关系,有利于lncRNA疗法的开发。     

胃癌相关长链非编码RNA的作用及其意义

近年来,研究显示长链非编码RNA(long non-coding RNA,lncRNA)与包括胃癌在内的多种人类肿瘤的发生发展有关.一些lncRNA可能作为胃癌诊断的生物标志物或治疗靶点.因此,探索lncRNA的具体功能,不仅有助于更好地了解胃癌的发病机制,而且对胃癌患者的个体化治疗极其重要.现结合国内外相关研究报道,...     

长链非编码RNA在肺癌中的研究进展

长链非编码RNA（LncRNA）是一类转录本长度超过200nt的RNA,不编码蛋白,大多数位于细胞核,以RNA的形式在多层面上（表观遗传调控、转录调控以及转录后调控等）调控基因的表达水平。其广泛参与机体的生理和病理过程,在恶性肿瘤的发生和发展中起着重要作用。     

Overexpression of long non-coding RNA UCA1 predicts a poor prognosis in patients with esophageal squamous cell carcinoma

Introduction: Long non-coding RNAs (lncRNAs) have been shown to have important regulatory roles in cancer biology, and the lncRNA UCA1 is upregulated in several cancers such as bladder cancer, breast cancer and colorectal cancer, however, the contributions of UCA1 to esophageal cancer remain largely unknown. Methods: Expression levels of lncRNA UCA1 in esophageal squamous cell carcinoma (ESCC) patients and esophageal cancer cell lines were evaluated by quantitative real-time PCR (qRT-PCR), and its association with overall survival of patients was analyzed by statistical analysis. Small interfering RNA was used to suppress UCA1 expression in esophageal cancer cell line. In vitro assays were conducted to further explore its underlying roles in tumor progression. Results: The relative level of UCA1 was significantly higher in ESCC tissues compared to the adjacent non-tumor tissues, and remarkably higher expression of UCA1 was found in esophageal cancer cell lines compared with the immortalized esophageal epithelial cell line NE1. The ESCC patients with higher UCA1 expression had an advanced clinical stage and a poorer prognosis than those with lower expression. In vitro assays, our data indicated that downregulation of UCA1 decrease cell proliferation, migration, and invasion ability. Conclusions: lncRNA UCA1 might be considered as a novel molecule involved in ESCC progression, which provides a potential prognostic biomarker and therapeutic target.     

DNA修复酶HOGG1在食管鳞癌的表达和临床意义

目的探讨食管鳞状上皮癌组织中DNA损伤修复酶HOGG1表达与8-oxoG氧化损伤的关系及其表达改变的临床意义。方法免疫组化和Western blot检测鳞癌和癌旁组织中HOGG1的表达和8-oxoG氧化损伤,TUNEL试剂盒检测组织的凋亡指数。相关性统计分析鳞癌组织HOGG1低表达与上述两项指标之间的相关性;χ2检验与秩和检验统计鳞癌组织中HOGG1低表达与临床病理特征之间的关系。结果 HOGG1在食管鳞癌患者的组织中均有不同程度的表达,并且存在个体差异,鳞癌组织中HOGG1表达明显低于其癌旁组织(P<0.05),8-oxoG的氧化损伤程度明显高于癌旁组织(P<0.05),鳞癌组织中HOGG1的低表达与该组织8-oxoG氧化损伤程度、细胞凋亡指数呈负相关,与鳞癌的静脉侵犯、淋巴结转移有关,与患者的年龄、性别、鳞癌组织的病理分化程度无关。结论 HOGG1可作为食管鳞癌术后的检测指标,指导患者术后个体化治疗方案的制定。     

食管鳞状细胞癌间质细胞中podoplanin的表达及临床意义

目的观察食管鳞状细胞癌间质细胞中podoplanin的表达及与临床病理特征的关系,探讨podoplanin阳性间质细胞在食管鳞状细胞癌进展中的作用。方法应用免疫组化En Vision法检测69例食管鳞状细胞癌中podoplanin的表达,分析阳性间质细胞中podoplanin表达与食管鳞状细胞癌临床病理特征的关系。结果 69例食管鳞状细胞癌中,间质细胞podoplanin阳性者43例,阳性率为62.3%。食管鳞状细胞癌中间质细胞podoplanin阳性者淋巴管密度(lymphatic vessel density,LVD)为45.72±14.36,明显高于间质细胞podoplanin阴性者(21.23±10.49),差异有统计学意义(P<0.01);有淋巴管侵犯的食管鳞状细胞癌间质细胞podoplanin表达明显高于无淋巴管侵犯者(P<0.05)。间质细胞podoplanin表达与患者年龄、性别、肿瘤大小、浸润深度、分化程度、淋巴结转移和临床分期均无关(P>0.05)。结论 podoplanin阳性间质细胞可促进食管鳞状细胞癌淋巴管形成和淋巴管侵犯。     

NOB1mRNA在人食管鳞癌组织的表达及其临床意义

目的 探讨NOB1 mRNA(nin one binding protein)在食管鳞癌(esophageal squamous cell carcinoma,ESCC)患者组织中的表达及其与临床病理参数之间的关系.方法 运用RT-PCR方法检测19例ESCC患者癌组织及对应的癌旁组织中NOB1 mRNA的表达情况,分...     

PINCH expression and its significance in esophageal squamous cell carcinoma

Particularly interesting new cysteine-histidine rich protein (PINCH), as a newly discovered protein of LIM family members, may play a role in signal transduction of integrin and growth factor, and involved in the incidence and development of tumors. PINCH protein is overexpressed in tumor-associated stroma of several types of tumors. However, there is no study of the PINCH in esophageal cancer, therefore we investigated PINCH expression in esophageal squamous cell carcinomas and its clinicopathological significance in the patients. PINCH expression was immunohistochemically examined in 20 normal esophageal samples and 64 esophageal squamous cell carcinomas. The results showed that PINCH expression in the stroma of cancers was heterogeneous, and its positive rate (56%) was higher than that of normal esophageal mucosa (5%, p<0.0001). The stronger staining was observed at the invasive edge of tumor when compared to the inner area of tumor. The rate of positive PINCH (90%) in the cases with lymph node metastasis was higher than that (41%) in the cases without metastasis (p<0.0001). PINCH expression was not correlated with patients' gender, age, tumor location, size and differentiation (p>0.05). The results suggest that PINCH protein may be a marker of tumor associated-stroma involving tumor development, and predicting the ability of invasion and metastasis of esophageal squamous cell carcinoma.     

Nrf2在食管鳞癌组织中的表达及意义

目的:探讨Nrf2(Nuclear factor E2 p45-related factor2)在食管鳞癌组织中的表达及其与临床病理学特征的关系。方法:采用免疫组化SP法检测Nrf2在32例食管鳞癌,30例癌旁组织,21个阳性淋巴结和24个阴性淋巴结组织中的表达。结果:Nrf2阳性表达主要定位于细胞核中,在食管鳞癌中的阳性表达率为78.13%,显著高于癌旁组织(13.33%),淋巴结癌转移阳性组织中的表达率(66.67%)也显著高于淋巴结癌转移阴性组织中的表达水平(20.83%),均具有统计学意义(P<0.05)。Nrf2的阳性表达随淋巴结的转移度的增加而表达增加(P<0.05),但在不同年龄、性别、TNM分期、肿瘤分化程度及不同部位之间差异无统计学意义。结论:Nrf2在食管鳞癌中高表达,表达的高低与淋巴结转移与否及转移度有关。     

Expression and clinical significance of B cell translocation gene 2 in esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma (ESCC) is widely known as a highly fatal cancer, and thus it is important to identify tumor-specific and radiosensitivity-specific markers in ESCC. B cell translocation gene 2 (BTG2) has been considered a novel tumor suppressor gene or radiotherapy sensitivity-associated gene. However, the relationship between BTG2 and ESCC development and radiotherapy sensitivity is uncertain. The present study aims to explore the expression and clinical significance of B cell translocation gene 2 (BTG2) in ESCC by analyzing the RNAseq data from the TCGA and immunohistochemical staining of ESCC samples. We found that the level of BTG2 mRNA was significantly decreased in ESCC patients, and further decreased significantly in radiotherapy resistant patients compared to sensitive patients. The positive expression rate of BTG2 protein was 56.0% (103/184) in 184 ESCC tissue samples and 84.0% (42/50) in normal esophageal mucosal samples, respectively. The positive ratios of BTG2 expression in radiotherapy-sensitive group and radiotherapy resistant group were 57.9% (22/38) and 23.5% (4/17), respectively. Furthermore, the analysis indicates that the expression level of BTG2 significantly correlated with lymph node metastasis and clinical staging in ESCC patients. A multivariate analysis with Cox regression model showed that BTG2 level was an independent risk factor affecting the prognosis of ESCC patients. Above all, the downregulation of BTG2 may be used as a molecular marker to identify and predict ESCC progression and radiosensitivity.     

Downregulation of long non-coding RNA B-Raf proto-oncogene-activated non-coding RNA reverses cisplatin resistance in laryngeal squamous cell carcinoma

IntroductionThis study was performed to explore the function of B-Raf proto-oncogene-activated non-coding RNA (BANCR) in laryngeal squamous cell carcinoma (LSCC) and cisplatin resistance.Material and methodsThe relative expression level of long non-coding RNA (lncRNA) BANCR was examined by qRT-PCR in tumor tissues and adjacent tissues, normal laryngeal cells (Het-1A) and laryngeal squamous carcinoma cells (TU686, TU177). Cisplatin-resistant laryngeal squamous carcinoma cell lines (TU686-DDP-R, TU177-DDP-R) were established. Next, we inhibited BANCR expression by transfecting siRNA-BANCR and enhanced BANCR expression by transfecting pcDNA3.1-BANCR into TU686, TU177, TU686-DDP-R and TU177-DDP-R cells. The CCK-8 assay and clone formation assay were performed to detect colony proliferation ability and formation ability of cells. Further, to investigate through which BANCR cell viability/formation is regulated, we detected the expression of MRP1, Bcl-2, p-PKB, and Bax by western blot.ResultsBANCR was highly expressed in laryngeal squamous carcinoma tissues and cells. Chemoresistance was generated in TU686-DDP-R and TU177-DDP-R compared with TU686 and TU177 cells after cisplatin treatment. In addition, upregulated lncRNA BANCR reduced or postponed cell sensitivity to cisplatin by enhancing cell proliferation in TU686 and TU177 cells. Meanwhile, the expression of MRP1, Bcl-2, and p-PKB was increased, while Bax was reduced. After cisplatin treatment, down-regulation of BANCR could consequently attenuate TU686-DDP-R and TU177-DDP-R cell proliferation, and the expression of MRP1, Bcl-2, and p-PKB was decreased and Bax was increased.ConclusionsDown-regulation of BANCR reverses cisplatin resistance of cisplatin-resistant LSCC cell lines.     

PTK7在食管鳞状细胞癌中的表达及临床意义

目的研究酪氨酸蛋白激酶-7（PTK7）在食管鳞状细胞癌、癌旁组织中的表达及其与食管鳞状细胞癌的发展、侵袭、淋巴结转移的关系,分析其在食管鳞癌中的诊断价值及预后变化。方法收集食管鳞状细胞癌标本80例及癌旁组织63例,采用免疫组织化学链霉菌抗生物素蛋白一过氧化物酶连结（SP）法检测PTK7蛋白的表达,结合临床相关因素进行x2检验及Kaplan—meier等统计学分析。结果80例患者食管鳞状细胞癌组织中有45例PTK7蛋白表达阳性（X2=50．17,P〈0．01）,食管癌旁非典型增生及正常鳞状上皮中PTK7蛋白表达均阴性。PTK7表达与食管鳞癌的年龄、性别、分化程度、浸润深度、淋巴结转移、浸润长度、临床分期等比较差异无统计学意义（P〉0．05）;与5年生存率比较差异亦无统计学意义（X2=0．2,P〉0．1）;当肿瘤组织PTK7蛋白表达综合免疫组化评分≥5分时,5年生存率有下降趋势（X2=3．35,P=0．06）。结论PTK7表达与食管鳞癌有关,当PTK7综合免疫评分≥5分时,5年生存率有下降趋势。利用检测PTK7的表达,有助于综合判断食管鳞癌的相关性和临床预后。