胰腺导管腺癌中CD74的表达及临床意义

目的 检测CD74蛋白在胰腺导管腺癌(pancreatic ductal adenocarcinoma,PDAC)组织中的表达并探讨其临床意义.方法 收集59例PDAC和23例慢性胰腺炎(chronic pancreatitis,CP)的存档石蜡包埋标本.HE染色、镜下观察神经纤维周围淋巴细胞病灶.免疫组化检测CD74的表达,统计分析其与PDAC临床病理参数的关系.结果 PDAC神经纤维周围淋巴细胞病灶发生率为67.8%.CD74在肿瘤细胞中阳性表达率为61%(36/59),明显高于CP导管上皮(13%,3/23,P=0.000).CD74表达与神经纤维淋巴细胞病灶密切相关(P=0.009),与其它临床病理参数无关.CD74阳性的PDAC患者术后生存时间明显短于CD74阴性患者(P=0.006 9).CD74在肿瘤细胞中的表达(P=0.009;rs=2.590)及Pt(P=0.022;rs=1.482)为影响PDAC患者预后的独立危险因素.结论 CD74在胰腺导管腺癌组织中高表达与神经纤维周围淋巴细胞病灶及肿瘤预后相关,可能成为PDAC预后相关的分子靶标.     

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<...     

胰腺导管腺癌中PDIA6和PD-L1的表达及其临床病理学意义

目的 探讨胰腺导管腺癌(pancreatic ductal adenocarcinoma, PDAC)中PDIA6和PD-L1的表达及与临床病理学特征和预后的相关性。方法 收集2013年1月～2019年12月郑州大学第一附属医院确诊的79例PDAC,采用免疫组化SP法检测PDIA6和PD-L1蛋白在PDAC中的表达,分析两者表达与临床病理特征及预后的关系。结果 79例PDAC中PDIA6和PD-L1的阳性率分别为57.0%(45/79)和7.6%(6/79),且PDIA6和PD-L1在PDAC中的表达均显著高于癌旁正常组织(P<0.05)。PDIA6表达与肿瘤出芽有关(P=0.035),与患者性别、年龄、肿瘤直径、肿瘤部位、分化程度、TNM分期、间质肿瘤浸润淋巴细胞、脉管内癌栓、神经侵犯、淋巴结转移等均无关(P>0.05);PD-L1表达与PDAC临床病理特征均无关(P>0.05)。PDAC预后的单因素生存分析结果显示,PDIA6(P=0.009)和PD-L1(P=0.040)表达与PDAC患者预后不良相关。此外,肿瘤出芽(P=0.016)、淋巴结转移(P<0....     

胰腺导管腺癌大切片中CD8的表达及预后分析

目的 探讨胰腺导管腺癌(pancreatic ductal adenocarcinoma,PDAC)大切片中T淋巴细胞相关抗原CD8的表达与临床病理特征及预后的关系.方法 收集57对术前未行新辅助治疗并经外科手术切除的PDAC石蜡样本大、小切片,采用免疫组化EnVision法检测CD8在大、小切片组的表达,分析其表达与...     

胰腺导管腺癌中DR5蛋白及mRNA的表达及临床意义

目的检测死亡受体5(death receptor 5,DR5)蛋白及mRNA在胰腺导管腺癌癌组织及癌旁正常组织中的表达及临床意义。方法采用免疫组化法检测DR5在117例胰腺导管腺癌石蜡包埋组织和癌旁正常组织中的表达,并对DR5蛋白表达与胰腺导管腺癌临床病理特征的关系进行系统性分析。同时利用qRT-PCR及Western blot法各检测20例配对的新鲜冻存的胰腺导管腺癌癌组织和癌旁正常组织中DR5蛋白及mRNA的表达。结果免疫组化结果显示,DR5主要表达于癌旁组织细胞的细胞膜中,DR5在胰腺导管腺癌组织中的阳性率为41. 02%(48/117),癌旁正常组织中的阳性率为74. 36%(87/117),两组表达差异有统计学意义(P 0. 001); DR5表达与分化程度(P 0. 05)、TNM分期(P 0. 05)、神经浸润(P 0. 001)以及淋巴结转移情况(P 0. 05)均有明显相关性。qRT-PCR及Western blot结果显示,癌旁正常组织中DR5蛋白及mRNA的表达量均远高于胰腺导管腺癌组织,两组相比差异有统计学意义(P 0. 001)。结论 DR5蛋白表达与胰腺导管腺癌分化程度、TNM分期、神经浸润及淋巴结转移均相关,对其进行检测可用于评估胰腺导管腺癌患者的病情严重程度及预后。     

胰腺导管腺癌中microRNA的研究进展

微小RNA(microRNA,miRNA)是近年来发现的、长度多在22～24个核苷酸广泛存在于动植物体内的非编码、单链RNA分子.研究表明miRNA参与生命过程中一系列的重要进程,包括早期发育、细胞增殖、分化、凋亡和免疫调节等.近年研究发现,miRNA与肿瘤的关系密切,不同miRNA在肿瘤的发生、发展、侵袭及转移等多个方面起到促进或抑制的作用.胰腺导管腺癌(pancreatic ductal adenocarcinoma,PDAC)是预后极差的恶性肿瘤,miRNA在PDAC中的研究为其诊断、治疗、评价预后及了解其恶性生物学行为带来新方向和新思路.     

胰腺导管腺癌患者血清中microRNA-155的表达及其临床意义

目的 检测microRNA-155(miR-155)在胰腺导管腺癌(pancreatic ductal adenocarcinoma,PDAC)组织中、患者血清中的含量,探讨其作为PDAC血清学诊断标志物的可能性.方法 应用荧光实时定量PCR法检测miR-155在20对PDAC组织和癌旁组织、70例PDAC患者和40例健康人血清、10对荷人PDAC小鼠和对照组小鼠血清及6株PDAC细胞株和其培养上清中的含量.结果 实验结果 显示,PDAC组织中miR-155表达高于癌旁胰腺组织(P=0.005);并且miR-155在PDAC患者血清中表达量高于健康对照组(P=0.004);在荷人PDAC小鼠血清中miR-155含量高于对照组小鼠(P=0.012);同时,6株PDAC细胞株miR-155的表达存在差异(P=0.000),miR-155在细胞内和在其培养上清中的表达具有高度一致性(r=0.628,P=0.005).结论 miR-155在PDAC组织和患者血清中表达上调,提示其可能是PDAC血清学的潜在标志物.     

长链非编码RNA WIF1-1在食管鳞状细胞癌组织中的表达及其临床意义

目的:探究食管鳞状细胞癌组织及癌旁组织中长链非编码RNA(long noncoding RNA,lncRNA)WIF1-1的表达水平,并评估其对患者预后的价值.方法:使用实时荧光定量PCR检测50例食管鳞状细胞癌组织样本及其对应同源的癌旁组织样本中lncRNA WIF1-1的表达水平,分析临床病理特征及其与患者预后的相关性.结果:食管鳞状细胞癌组织中lncRNA WIF1-1的表达水平明显低于癌旁组织,差异有统计学意义(P<0.001).进一步分析发现:lncRNA WIF1-1的表达水平与食管鳞状细胞癌的淋巴结转移、TNM分期和临床分期之间呈负相关.对预后资料分析发现:lncRNA WIF1-1表达水平较低的食管鳞癌患者的总生存时间(overall survival,OS)以及无进展生存期(progression-free survival,PFS)均较短.单因素及多因素分析结果显示:lncRNA WIF1-1可作为食管鳞状细胞癌患者OS和PFS的独立危险因素.结论:lncRNA WIF1-1可能在食管鳞状细胞癌中发挥抑癌基因的作用,其表达量与患者预后具有相关性,有可能成为食管鳞状细胞癌的治疗靶点.     

胰腺导管腺癌中胰腺星形细胞的研究进展

胰腺星形细胞(pancreatic stellate cells,PSC)是胰腺导管腺癌(pancreatic ductal adenocarcinoma,PDAC)肿瘤微环境中最重要的成分,在PDAC发生发展中具有非常关键的作用.目前大量研究关注于PSC与胰腺癌细胞(pancreatic cancer cells,PCC)之间的相互作用及PSC在PDAC微环境中发挥的作用.PSC在许多情况下发生活化,如乙醇、氧化应激和高血糖等.PDAC早期即可出现PSC的活化,PCC可以诱导刺激PSC发生活化,活化的PSC可以产生大量胶原纤维,形成适宜PCC生长的间质微环境,促进PCC的增殖,减少化疗药物对肿瘤细胞的杀伤作用.另外,PSC还可以与间质中各种细胞成分如内皮细胞和各种免疫细胞相互作用,在血管生成、免疫逃逸和神经侵犯等方面协助肿瘤进展.因此,阐明PSC与肿瘤细胞以及其他间质成分之间复杂的相互作用至关重要.     

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...     

Expression of long non-coding RNA LOC285194 and its prognostic significance in human pancreatic ductal adenocarcinoma

Introduction: Dysregulation of long non-coding RNAs (lncRNAs) plays critical roles in tumor progression. lncRNA LOC285194 was previously shown to be correlated with aggressive clinicopathological features and poor prognosis in several cancers. The aim of this study was to investigate relationship between LOC285194 expression and clinical outcomes in human pancreatic ductal adenocarcinoma (PDAC). Methods: Quantitative real-time PCR (qRT-PCR) assay was performed to detect the expression of lncRNA LOC285194 in human PDAC cells and tissue samples. The association of LOC285194 expression with clinicopathologic features was analyzed. Kaplan-Meier analyses were used to assess survival of patients. Univariate and multivariate analyses were performed using the Cox proportional hazards model to analyze the prognostic significance of LOC285194 expression. Results: Our data showed that the relative level of LOC285194 in PDAC cells was significantly lower than that in normal human pancreatic duct epithelial cell line. Also, the expression of LOC285194 in PDAC tissues was significantly lower than that in adjacent non-tumor tissues. By statistical analyses, low LOC285194 expression was observed to be closely correlated with clinical stage, lymphnode metastasis and liver metastasis. Kaplan-Meier survival analysis revealed that patients with low LOC285194 expression had a poor overall survival compared with the high LOC285194 group (P < 0.05). Univariate and multivariate analyses showed that low LOC285194 expression was an independent poor prognostic factor for PDAC patients. Conclusions: Our data provided the first evidence that reduced LOC285194 in PDAC tissues was correlated with tumor progression, and lncRNA LOC285194 might be a potential molecular biomarker for predicting the prognosis of patients.     

PNMA1 promotes cell growth in human pancreatic ductal adenocarcinoma

Paraneoplastic Ma1 (PNMA1) is a member of an expanding family of ‘brain/testis’ proteins involved in an autoimmune disorder defined as paraneoplastic neurological syndrome (PNS). Although it is widely studied in PNS, little is known about the underlying clinical significance and biological function of PNMA1 in tumors. Here, we find that elevated PNMA1 expression is more commonly observed in pancreatic ductal adenocarcinoma (PDAC) cell lines, compared with normal pancreatic cell and tissues from pancreatic ductal adenocarcinoma patient. Besides, higher PNMA1 expression is closely correlated with large tumor size. Suppression of endogenous PNMA1 expression decreases cell viability and promotes cell apoptosis. Subsequent studies reveal that the PI3K/AKT, MAPK/ERK pathway and members of the anti-apoptotic Bcl-2 family may be involved in the pro-survival and anti-apoptotic effect of PNMA1 on PDAC. Taken together, this study provides evidence that PNMA1 is involved in tumor growth of pancreatic carcinoma and PNMA1-related pathways might represent a new treatment strategy.     

Abnormal expression of Nek2 in pancreatic ductal adenocarcinoma: a novel marker for prognosis

Nek2 is a serine/threonine kinase that has a critical role in mitosis during the cell division process. Despite its importance in centrosome regulation and spindle formation, no direct binders are reported between human pancreatic cancer and Nek2 protein. Our aim in studying Nek2 expression and survival in PDA patients is to determine whether Nek2 is a valuable prognostic factor in PDA tumorigenesis. We found that Nek2 mRNA was elevated in PDA tissues. A high level of expression of Nek2 was significantly correlated with histological differentiation (P=0.042), lymph node metastasis (P=0.003) and tumor stage (P=0.001). Patients with a high Nek2 expression had a significantly worse overall survival (OS) than those patients with low Nek2 expression (P=0.002). Univariate and multivariate analysis revealed that high expression of Nek2 could serve as an independent predictor of poor prognosis. These results indicate that Nek2 could be a promising prognostic molecular marker and an attractive therapeutic target for PDA.     

Molecular pathogenesis of pancreatic ductal adenocarcinoma

The statistics are alarming; pancreatic ductal adenocarcinoma (PDA) will be the second leading cause of death amongst all cancers by 2020. More worrisome is that incidence is on the rise, and without more effective cancer control of this disease, the trajectory of the virtually indistinguishable rates of incidence and mortality will remain the reality for years to come. Advances in genomics are beginning to clarify the key issues about the pathogenesis of this aggressive tumour type. New insights into classic pathogenic driver genes, such as KRAS, CDKN2A, TP53 and SMAD4, are portraying alternative roles for these genes beyond their function at the preneoplastic level including metastatic dissemination and chemoresistance. Clinically relevant molecular subtypes have recently emerged, which will aid oncologists in making more informed treatment decisions to improve outcomes in the future. A wealth of data surrounding these issues has been generated over the last 5 years. Below, we attempt to bring readers up to speed on recent research findings in PDA.     

Prognostic significance of long non-coding RNA PCAT-1 expression in human hepatocellular carcinoma

Background: Long non-coding RNAs (lncRNAs) play widespread roles in gene regulation and cellular processes. However, the functional roles of lncRNAs in hepatocellular carcinoma (HCC) are not yet well elucidated. The aim of the present study was to measure the levels of lncRNA PCAT-1 expression in HCC and evaluate its clinical significance in the development and progression of HCC. Methods: We examined the expression of PCAT-1 in 117 HCC tissues and adjacent non-tumor tissues using quantitative real-time-PCR and analyzed its correlation with the clinical parameters. Results: Our data showed that PCAT-1 expression in HCC tissues was significantly increased compared with adjacent non-tumor tissues (P<0.05). Up-regulated expression of PCAT-1 was significantly associated with TNM stage and metastasis (P<0.05), but not other clinical parameters. Moreover, Kaplan-Meier survival analysis showed that a high expression level of PCAT-1 resulted in a significantly poor overall survival of HCC patients. The multivariate Cox regression analysis demonstrated that PCAT-1 expression level was an independent prognostic factor for the overall survival rate of HCC patients. Conclusions: Our data suggested that the increased expression of PCAT-1 was associated with advanced clinical parameters and poor overall survival of HCC patients, indicating that PCAT-1 up-regulation may serve as a novel biomarker of poor prognosis in HCC patients.     

EGFR expression in pancreatic intraepithelial neoplasia and ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDA) is an aggressive malignant tumor with poor prognosis. Epidermal growth factor receptor (EGFR) is an important cell adhesion and signaling pathway mediator. The aim of this study was to evaluate the expression of EGFR in both pancreatic intraepithelial neoplasia (PanIN) and PDA and their relationship to clinicopathologic characteristics. Formalin-fixed, paraffin-embedded tissues including 81 cases with pancreatic ductal adenocarcinoma, 27 with normal pancreas, 16 with PanIN-1A, 18 with PanIN-1B, 11 with PanIN-2, and 24 with PanIN-3 were used for construction of tissue microarrays. Imunohistochemistry for EGFR was performed. Normal pancreatic ducts, PanIN-1A, and PanIN-1B did not show EGFR overexpression. EGFR overexpression was observed in 18.2% (2/9) of PanIN-2, 41.7% (10/14) of PanIN-3, and 64.2% (52/81) of PDA, respectively. Significantly higher EGFR overexpression was observed in PDAs than in PanIN lesions (P<0.05). No statistically significant correlation was observed between EGFR overexpression and patient age, sex, tumor location, size, histological grade, vascular invasion, lymph node metastasis and stage at presentation, respectively. In conclusion, EGFR expression increased from PanIN to PDA. EGFR may be involved in early stage in development of PDA.     

Low expression of nucleus accumbens‐associated protein 1 predicts poor prognosis for patients with pancreatic ductal adenocarcinoma

Nucleus accumbens‐associated protein 1 (NAC1) is overexpressed in various carcinomas including ovarian, cervical, breast, and pancreatic carcinomas. High expression of NAC1 is considered to have adverse effects on prognosis through negative regulation of growth arrest and DNA‐damage–inducible 45‐γ interacting protein 1 (GADD45GIP1) in ovarian and cervical carcinomas. In the present study, the expression of NAC1 in pancreatic ductal adenocarcinoma (PDA) was measured using immunohistochemistry and computer‐assisted image analysis in order to investigate its correlation with various clinicopathological parameters and prognosis. Patients with low‐NAC1 PDA had worse overall survival (P = 0.0010) and a shorter disease‐free survival (P = 0.0036) than patients with high‐NAC1 PDA. This was a clinical effect opposite to that reported in ovarian and cervical carcinomas. Furthermore, knockdown of NAC1 in pancreatic carcinoma cell lines did not increase expression of the GADD45GIP1 protein. These results indicate that the gene(s) regulated by NAC1 vary depending on the types of carcinoma or originating tissue, and that low expression of NAC1 predicts poor prognosis for patients with PDA.     

Expression of urocortin in pancreatic ductal adenocarcinoma and pancreatic intraepithelial neoplasia

Urocortin (UCN) is a 40‐aminoacid neuropeptide that regulates angiogenesis and inhibits cell proliferation. Our aim was to examine the relationship of UCN expression to the clinicopathological parameters of pancreatic ductal adenocarcinoma (PDAC) and histological grade of pancreatic intraepithelial neoplasia (PanIN). Tissue microarray was used to analyze UCN protein expression in 89 surgical specimens including 21 PanIN, 3 PDAC arising from PanIN, and 65 PDAC without PanIN. UCN immunoscores ranging from 0 to 12 were obtained by multiplying intensity (scored on a 3‐point scale) by the percentage of stained cells (scored on a 4‐point scale). Strong expression of UCN was detected in 5 specimens of non‐neoplastic pancreatic ductal epithelia. UCN immunoscore was significantly higher in PanIN‐1 than in PanIN‐2 and PanIN‐3 (p = 0.038) and significantly higher in well‐differentiated PDAC or early American Joint Committee on Cancer (AJCC) stage PDAC than in poorly differentiated or advanced stage PDAC (p = 0.025, p = 0.018). Higher expression of UCN correlates with PDAC tumor grade and AJCC pathologic stage as well as PanIN grade. Immunohistochemical assessment of UCN may help clinicians predict tumor recurrence rate and help pathologists make a proper diagnosis.     

Concentrations of trace elements and KRAS mutations in pancreatic ductal adenocarcinoma

Trace elements are a possible risk factor for pancreatic ductal adenocarcinoma (PDAC). However, their role in the occurrence and persistence of KRAS mutations remains unstudied. There appear to be no studies analyzing biomarkers of trace elements and KRAS mutations in any human cancer. We aimed to determine whether patients with KRAS mutated and nonmutated tumors exhibit differences in concentrations of trace elements. Incident cases of PDAC were prospectively identified in five hospitals in Spain. KRAS mutational status was determined through polymerase chain reaction from tumor tissue. Concentrations of 12 trace elements were determined in toenail samples by inductively coupled plasma mass spectrometry. Concentrations of trace elements were compared in 78 PDAC cases and 416 hospital-based controls (case–control analyses), and between 17 KRAS wild-type tumors and 61 KRAS mutated tumors (case–case analyses). Higher levels of iron, arsenic, and vanadium were associated with a statistically nonsignificant increased risk of a KRAS wild-type PDAC (OR for higher tertile of arsenic = 3.37, 95% CI 0.98–11.57). Lower levels of nickel and manganese were associated with a statistically significant higher risk of a KRAS mutated PDAC (OR for manganese = 0.34, 95% CI 0.14–0.80). Higher levels of selenium appeared protective for both mutated and KRAS wild-type PDAC. Higher levels of cadmium and lead were clear risk factors for both KRAS mutated and wild-type cases. This is the first study analyzing biomarkers of trace elements and KRAS mutations in any human cancer. Concentrations of trace elements differed markedly between PDAC cases with and without mutations in codon 12 of the KRAS oncogene, thus suggesting a role for trace elements in pancreatic and perhaps other cancers with such mutations. Environ. Mol. Mutagen., 60:693–703, 2019. © 2019 Wiley Periodicals, Inc.