Identification of hemoglobin-alpha and -beta subunits as potential serum biomarkers for the diagnosis and prognosis of ovarian cancer

The development of new biomarkers for ovarian cancer is clearly necessary for the improved detection and monitoring of the disease. Surface enhanced laser desorption and ionization time-of-flight mass spectrometry (SELDI-TOF-MS) can be employed in the identification of differentially expressed proteins in cancer cells. The objective of this study was, then, to identify potential diagnostic serological biomarkers for ovarian cancer. We performed protein expression difference analyses of 45 serum samples using SELDI protein chip array. Forty-five sera obtained from ovarian cancer patients (n=35) and normal healthy females (n=10), were profiled on the surface of SELDI protein chip. The candidate biomarkers were purified by CM-Sepharose, and their N-terminal amino sequence was determined. The amounts of hemoglobin (Hb) in cancer patient's sera versus that of normal sera were measured by ELISA. Nine sera proteins that were found to be significantly differentially expressed (P<0.05) between the sera of ovarian cancer patients and that of normal healthy females were selected using the WCX2 array. The most distinctive polypeptide peaks detected in the ovarian cancer samples were at 15.1 and 15.8 kDa and these two peaks were identified as the hemoglobin-alpha (Hb-alpha) and -beta (Hb-beta) chain, respectively. ELISA indicated that the sensitivity for intact Hb level was 77% in sera obtained from ovarian cancer patients, as compared with normal healthy female sera. In conclusion, two ovarian cancer biomarker proteins were discovered and identified as Hb-alpha and Hb-beta. Hb levels were significantly different in ovarian cancer serum samples and those obtained from normal healthy females, as determined by ELISA. Additional studies are required to further validate Hb-alpha and Hb-beta biomarkers.     

Cell-free 59 kDa immunoreactive integrin-linked kinase: a novel marker for ovarian carcinoma.

PURPOSE: We reported that the expression of integrin-linked kinase (ILK) is up-regulated in ovarian carcinomas and that ovarian cancer cells have high expression of ILK. In this study, we have examined the expression of cell-free 59 kDa immunoreactive (ir)ILK in the serum and peritoneal fluid (PTF) of patients with ovarian cancer and evaluated its potential as a serum biomarker for early-stage screening and for monitoring clinical status of patients after chemotherapy treatment. EXPERIMENTAL DESIGN: Thirty-six serum specimens, including normal (n = 6), benign (n = 6), borderline (n = 4), grade 1 (n = 5), grade 2 (n = 5), and grade 3 (n = 10), were evaluated for the expression of irILK by Western blotting. The expression of irILK was evaluated in PTF (n = 10) and peritoneal washings from women with benign ovarian cysts (n = 4). In addition, tissue-conditioned medium obtained from the cultures of primary ovarian tumors (n = 9) was examined for the presence of irILK. Finally, the potential of serum irILK as a biomarker for ovarian cancer screening was evaluated by comparison with cancer antigen 125 (CA 125) concentrations in cancer patients before and after chemotherapy. RESULTS: irILK expression was present in normal serum and in serum of patients with benign ovarian tumors. irILK expression was 6-9-fold higher in the serum of patients with grade 1, grade 2, and grade 3 ovarian cancer than in the serum of healthy volunteers and patients with benign ovarian tumors (P < 0.01). Enhanced expression of irILK in the serum of ovarian cancer patients correlated with the concentration of CA 125. High expression of irILK was present in all 10 PTF tested. Tissue-conditioned medium prepared from malignant ovarian tumors had 4-fold more irILK expression than conditioned medium obtained from borderline and benign tumors (P < 0.01). irILK expression in serum of cancer patients was reduced to basal normal levels after six cycles of Taxol/carboplatin and was consistent with the change of CA 125 levels before and after chemotherapy. CONCLUSIONS: These data suggest that irILK is an ovarian tumor-associated antigen and implicates its potential not only as a biomarker for early-stage screening but also as a marker for monitoring the clinical condition of patients after treatment.     

表面增强激光解析电离飞行时间质谱技术在前列腺癌蛋白质组研究中的应用

目的应用表面增强激光解析电离飞行时间质谱（SELDI—TOF—MS）和蛋白质芯片技术分析前列腺癌（PCa）差异蛋白表达及其与病理分级和临床分期的关系,初步探讨雄激素难治性前列腺癌（HRPC）的发病机制。方法以病理确诊的PCa和良性前列腺增生（BPH）各45例,另以HRPC与激素依赖性前列腺癌（ADPC）各21例患者血清为研究对象,采用SELDI—TOF-MS固相金属亲和芯片技术检测血清的蛋白表达图谱,用BiomarkerWizard软件分析差异蛋白。结果在PCa和BPH患者血清中检测到9个差异蛋白（P〈0．01）,各差异蛋白在不同病理分级间表达差异有统计学意义。HRPC与ADPC有6个血清蛋白表达,差异有统计学意义（P〈0．05）。结论通过SELDI—TOF—MS蛋白质芯片技术检测PCa的标志蛋白可以提高PCa诊断的敏感度和特异度;差异蛋白在PCa不同病理分级间表达差别可能与PCa分化、肿瘤侵袭生长有关。HRPC与ADPC患者血清的差异蛋白可能在ADPC向HRPC转变过程中发挥着重要作用,检测差异蛋白可以明确诊断,评估预后,指导治疗。     

Prostasin, a potential serum marker for ovarian cancer: identification through microarray technology

BACKGROUND: Screening biomarkers for ovarian cancer are needed because of its late stage at diagnosis and poor survival. We used microarray technology to identify overexpressed genes for secretory proteins as potential serum biomarkers and selected prostasin, a serine protease normally secreted by the prostate gland, for further study. METHODS: RNA was isolated and pooled from three ovarian cancer cell lines and from three normal human ovarian surface epithelial (HOSE) cell lines. Complementary DNA generated from these pools was hybridized to a microarray slide, and genes overexpressed in the cancer cells were identified. Real-time quantitative polymerase chain reaction was used to examine prostasin gene expression in ovarian cancer and HOSE cell lines. Anti-prostasin antibodies were used to examine prostasin expression and to measure serum prostasin by an enzyme-linked immunosorbent assay in 64 case patients with ovarian cancer and in 137 control subjects. Previously determined levels of CA 125, an ovarian cancer marker, were available from about 70% of all subjects. All statistical tests were two-sided. RESULTS: Prostasin was detected by immunostaining more strongly in cancerous ovarian epithelial cells and stroma than in normal ovarian tissue. The mean level of serum prostasin was 13.7 microg/mL (95% confidence interval [CI] = 10.5 to 16.9 microg/mL) in 64 case patients with ovarian cancer and 7.5 microg/mL (95% CI = 6.6 to 8.3 microg/mL) in 137 control subjects (P<.001, after adjustment for the subject's age, year of collection, and specimen quality). In 14 of 16 case patients with both preoperative and postoperative serum samples, postoperative prostasin levels were statistically significantly lower than preoperative levels (P =.004). In 37 case patients with nonmucinous ovarian cancer and in 100 control subjects for whom levels of CA 125 and prostasin were available, the combination of markers gave a sensitivity of 92% (95% CI = 78.1% to 98.3%) and a specificity of 94% (95% CI = 87.4% to 97.7%) for detecting ovarian cancer. CONCLUSIONS: Prostasin is overexpressed in epithelial ovarian cancer and should be investigated further as a screening or tumor marker, alone and in combination with CA 125.     

LncRNA PVT1及PD-L1表达与顺铂耐药上皮性卵巢癌临床病理特征及预后的相关性分析

  目的  探讨顺铂耐药性上皮性卵巢癌（cisplatin resistant epithelial ovarian cancer,CREOC）患者的长链非编码核糖核酸（long non-coding ribose nucleic acid,LncRNA）的浆细胞瘤异位基因1（plasma cytoma variant translocation1,PVT1）和程序性死亡配体1（programmed cell death-ligand 1,PD-L1）的表达关系及其作用。  方法  收集2014年1月至2017年12月139例于天津医科大学肿瘤医院经病理诊断为上皮性卵巢癌患者的临床病理资料,采用实时荧光定量PCR（real-time fluorescent quantitative PCR,RT-qPCR）和免疫组织化学法分别检测CREOC组织中的LncRNA PVT1和PD-L1表达,分析其与临床病理特征及预后的相关性。  结果  CREOC组织中的LncRNA PVT1和PD-L1表达均显著高于正常卵巢组织（P < 0.05）。CREOC组织中的LncRNA PVT1和PD-L1表达呈正相关（r=0.629,P < 0.001）。LncRNA PVT1和PD-L1的高表达与组织学分级、FIGO分期和淋巴结转移有关（P < 0.05）。Ln? cRNA PVT1高表达与残留病灶大小、血清CA125水平有关（P < 0.05）。单因素Logistic生存分析显示,LncRNA PVT1和PD-L1的高表达患者的无进展生存期（progression-free survival,PFS）和总生存期（overall survival,OS）明显低于LncRNA PVT1和PD-L1的低表达者（P < 0.05）。  结论  CREOC患者组织中LncRNA PVT1和PD-L1的表达明显增高,且LncRNA PVT1的表达与PD-L1呈正相关。LncRNA PVT1和PD-L1的高表达与CREOC患者临床病理特征中的更具侵袭性及较差的预后相关。      

卵巢癌患者血清CEA、SCCA和Cyfra21-1含量的检测价值

目的探讨卵巢癌患者血清CEA、SCCA和Cyfra21-1含量的检测价值。方法选择卵巢交界性肿瘤40例(交界组)和上皮性卵巢癌90例(卵巢癌组),检测所有患者的血清CEA、SCCA和Cyfra21-1含量,并进行相关性分析和诊断价值判断。结果卵巢癌组的血清CEA、SCCA和Cyfra21-1含量都显著高于交界组(P<0.05)。卵巢癌组的CEA、SCCA和Cyfra21-1阳性表达率分别为95.0%、80.0%、90.0%,显著高于交界组37.8%、36.6%、30.0%(P<0.05)。在130例患者中,Spearman等级相关分析显示CEA、SCCA和Cyfra21-1阳性率与上皮性卵巢癌存在显著正相关性(P<0.05)。ROC曲线分析显示CEA、SCCA和Cyfra21-1鉴别诊断卵巢交界性肿瘤和上皮性卵巢癌曲线下最大面积分别为0.766、0.674、0.714。结论血清CEA、SCCA和Cyfra21-1在上皮性卵巢癌中呈现高表达状态,与卵巢癌的发生显著相关,可用来鉴别诊断卵巢交界性肿瘤和上皮性卵巢癌。     

前列腺癌的差异蛋白及其临床意义的研究

目的应用表面增强激光解析电离飞行时间质谱（SELDI-TOF-MS）和蛋白质芯片技术,探讨前列腺癌差异蛋白表达及其与病理分级和临床分期的关系。方法以病理确诊的前列腺癌和良性前列腺增生各45例为研究对象,采用SELDI-TOF-MS蛋白质芯片技术检测血清的蛋白表达图谱,用Biomarker Wizard软件分析差异蛋白,对所得差异蛋白进一步分析。结果在前列腺癌和良性前列腺增生患者血清中检测到9个差异蛋白（P〈0.01）,前列腺癌患者血清差异蛋白7个高表达,2个低表达。各差异蛋白在不同病理分级间表达差异有统计学意义。结论通过SELDI-TOF-MS蛋白质芯片技术检测前列腺癌的特异蛋白可以提高前列腺癌诊断的敏感性和特异性。差异蛋白在前列腺癌不同病理分级间表达差别可能与前列腺癌分化、肿瘤侵袭生长有关,检测差异蛋白可以明确诊断,评估预后,指导治疗。     

ASPM and microcephalin expression in epithelial ovarian cancer correlates with tumour grade and survival

Background:

The clinico-pathological and molecular heterogeneity of epithelial ovarian cancer (EOC) complicates its early diagnosis and successful treatment. Highly aneuploid tumours and the presence of ascitic fluids are hallmarks of EOC. Two microcephaly-associated proteins, abnormal spindle-like microcephaly-associated protein (ASPM) and microcephalin, are involved in mitosis and DNA damage repair. Their expression is deregulated at the RNA level in EOC. Here, ASPM and microcephalin protein expression in primary cultures established from the ascites of patients with EOC was determined and correlated with clinical data to assess their suitability as biomarkers.

Methods:

Five established ovarian cancer cell lines, cells derived from two benign ovarian ascites samples and 40 primary cultures of EOC derived from ovarian ascites samples were analysed by protein slot blotting and/or immunofluorescence to determine ASPM and microcephalin protein levels and their cellular localisation. Results were correlated with clinico-pathological data.

Results:

A statistically significant correlation was identified for ASPM localisation and tumour grade, with high levels of cytoplasmic ASPM correlating with grade 1 tumours. Conversely, cytoplasmic microcephalin was only identified in high-grade tumours. Furthermore, low levels of nuclear microcephalin correlated with reduced patient survival.

Conclusion:

Our results suggest that ASPM and microcephalin have the potential to be biomarkers in ovarian cancer.     

血清miR-21、miR-200a水平变化与卵巢癌发生发展的关系

目的探讨血清中微小RNA21(miR-21)、微小RNA200a(miR-200a)的表达变化与卵巢癌发生发展的关系。方法选取90例上皮性卵巢癌患者为病例组、同期健康体检妇女90例为对照组;采用实时荧光定量PCR技术检测2组人群血清中的miR-21、miR-200a水平;并分析不同临床分期、病理学分级、病理学类型、淋巴结转移、病灶大小的卵巢癌患者血清中的miR-21、miR-200a水平差异。结果病例组患者的血清中miR-21、miR-200a表达水平显著高于对照组,差异具有统计学意义(P<0.05)。卵巢癌患者的血清中miR-21表达水平在不同的临床分期、不同组织学分化程度、是否发生淋巴结转移的患者中比较,差异具有统计学意义(P<0.05);卵巢癌患者的血清中miR-200a表达水平在不同组织学分化程度的患者中比较,差异具有统计学意义(P<0.05)。结论卵巢癌患者的血清miR-21、miR-200a水平表达显著升高,可能与卵巢癌的发生发展具有一定的关系。     

卵巢癌新辅助化疗后Hedgehog信号通路改变的研究

目的 探究顺铂作用于卵巢癌后Hedgehog信号通路相关蛋白表达的变化.方法 应用免疫组织化学染色法检测80例卵巢癌标本中PTCH1蛋白表达水平与卵巢癌病理特征(病理类型、病理分级、淋巴结转移、临床分期)以及患者术前是否行新辅助化疗的关系.常规培养卵巢癌细胞OVCAR-3;顺铂干预后Western Blot法观察细胞PTCH1、CycllinD1及Gli1表达水平的变化情况;CCK-8法检测细胞增殖能力的变化.结果 PTCH1在卵巢癌组织中的表达呈阳性;PTCH1蛋白的表达在不同病理类型、临床分期、组织学分级、淋巴结转移的卵巢癌患者中,差异均无统计学意义(P﹥0.05);但经顺铂新辅助化疗的卵巢癌患者的卵巢癌组织中PTCH1的阳性率较未行新辅助化疗的患者低(P﹤0.05).实验组PTCH1、CyclinD1、Gli1蛋白的相对表达量较对照组低(P﹤0.05);在顺铂干预24 h后,相同时间点上,实验组的细胞增殖率均低于对照组(P﹤0.05).结论 顺铂可能通过干扰卵巢癌中Hedgehog通路关键因子从而影响卵巢癌的发生发展.     

Clinical value of serum tumor supplied group of factor in diagnosis of epithelial ovarian cancer

Tumor supplied group of factor (TSGF), whose original name was tumor specific growth factor, is a new tumor marker associated with vascular proliferation of malignant tumor. We investigated the correlation of the serum level of TSGF with VEGF and CA125 in patients with epithelial ovarian cancer and benign ovarian lesion, and compared their clinical diagnostic value for epithelial ovarian cancer. MATERIALS AND METHODS Clinical Materials During the period from Sep. 1997 to Sep…     

Proteomic-based analysis for identification of potential serum biomarkers in gallbladder cancer

Gallbladder cancer is the most common malignant tumor of the biliary tract. Early diagnosis of gallbladder cancer is difficult because of the latent onset and lack of good biomarkers. To identify new biomarkers that improve the early diagnosis and/or serve as possible therapeutic targets in gallbladder cancer is essential. In the present study, serum proteins were separated by two-dimensional gel electrophoresis (2-DE) in 3 patients with gallbladder cancer and 3 healthy volunteers. The differentially expressed spots were identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Western blotting and immunohistochemistry were performed to verify the expression of certain candidate proteins. Protein expression and clinical correlation was evaluated. We found that 64 protein spots were significantly changed in gallbladder cancer. Twenty-four proteins including S100A10, haptoglobin, cystatin-B, profilin-1 and superoxide dismutase were successfully identified. Among these proteins, S100A10 and haptoglobin were validated using Western blotting. Immunohistochemically, the expression of S100A10 and haptoglobin proteins was found to be higher in gallbladder cancer tissues compared to that in gallbladder adenoma, liver cholangiocarcinoma and cholecystitis tissue. Patients with high expression of S100A10 and haptoglobin were linked to late stage disease and poor clinical prognosis. Our data suggest that combined comparative proteomic analysis by 2-DE and MALDI-TOF-MS is an effective method for identifying differentially expressed proteins in serum samples. These proteomic approaches could be used for identifying new serum biomarkers in gallbladder cancer. S100A10, haptoglobin and other identified proteins may be potential molecular targets for early gallbladder cancer diagnostics and therapeutic applications.     

浆细胞瘤多样异位基因1 在卵巢癌组织中的表达及其对SKOV3 细胞恶性生物学行为的影响

目的：研究人浆细胞瘤多样异位基因1（plasma-cytoma variant translocation gene 1, PVT1）对卵巢癌SKOV3 细胞增殖、迁移和侵袭能力的影响。方法：选取2015年11 月至2017 年4 月郑州大学第三附属医院妇产科收治的卵巢癌患者32例。利用实时荧光定量PCR检测PVT1 在32例卵巢癌组织及癌旁组织的表达。通过CCK-8法、划痕法及Transwell法检测PVT1 对卵巢癌细胞增殖、迁移及侵袭能力的影响。结果：PVT1在SKOV3细胞和卵巢癌组织表达水平均明显升高（均P<0.01）;PVT1表达水平与卵巢癌者组织学分级、FIGO分期及淋巴结转移具有相关性（P<0.05或P<0.01）。转染PVT1 siRNA36、48 h 后,SKOV3细胞中PVT1 表达水平明显下降（P<0.05）;敲减PVT1的表达能够降低SKOV3细胞的增殖能力（P<0.05）,抑制SKOV3细胞增殖、迁移和侵袭能力（P<0.05或P<0.01）。结论：PVT1 在卵巢癌中高表达,抑制PVT1表达能够抑制卵巢癌SKOV3细胞增殖、迁移和侵袭能力。     

Neutrophil gelatinase-associated lipocalin (NGAL) an early-screening biomarker for ovarian cancer: NGAL is associated with epidermal growth factor-induced epithelio-mesenchymal transition

The expression of neutrophil gelatinase-associated lipocalin (NGAL) has been shown to be upregulated in ovarian cancer cells. In this study, we report that the expression of immunoreactive NGAL (irNGAL) in ovarian tumors changes with disease grade and that this change is reflected in the concentration of NGAL in peripheral blood. A total of 59 ovarian tissues including normal, benign, borderline malignant and grades 1, 2 and 3 malignant were analyzed using immunohistochemistry. irNGAL was not present in normal ovaries and the NGAL expression was weak to moderate in benign tissues. Both borderline and grade 1 tumors displayed the highest amount of NGAL expression with moderate to strong staining, whereas in grade 2 and 3 tumors, the extent of staining was significantly less (p < 0.01) and staining intensity was weak to moderate. Staining in all cases was confined to the epithelium. NGAL expression was analyzed by ELISA in 62 serum specimens from normal and different grades of cancer patients. Compared to control samples, the NGAL concentration was 2 and 2.6-fold higher in the serum of patients with benign tumors and cancer patients with grade 1 tumors (p < 0.05) and that result was consistent with the expression of NGAL performed by Western blot. NGAL expression was evaluated by Western blot in an immortalized normal ovarian cell line (IOSE29) as well as ovarian cancer cell lines. Moderate to strong expression of NGAL was observed in epithelial ovarian cancer cell lines SKOV3 and OVCA433 while no expression of NGAL was evident in normal IOSE29 and mesenchyme-like OVHS1, PEO.36 and HEY cell lines. NGAL expression was downregulated in ovarian cancer cell lines undergoing epithelio-mesenchymal transition (EMT) induced by epidermal growth factor (EGF). Downregulation of NGAL expression correlated with the upregulation of vimentin expression, enhanced cell dispersion and downregulation of E-cadherin expression, some of the hallmarks of EMT. EGF-induced EMT phenotypes were inhibited in the presence of AG1478, an inhibitor of EGF receptor tyrosine kinase activity. These data indicate that NGAL may be a good marker to monitor changes of benign to premalignant and malignant ovarian tumors and that the molecule may be involved in the progression of epithelial ovarian malignancies.     

应用SELDI-TOF-Ms技术筛选血清蛋白标志物以建立胃癌早期的诊断模型

Objective:Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry(SELDI-TOF-MS) is one of the currently used techniques to identify biomarkers for cancers.This study was planned to make a proteomic analysis on the serum of stage I gastric cancer patients and establish a early diagnostic model for identifying stage I gastric cancer preliminarily.Methods:A total of 229 serum samples including 169 pathologically confirmed gastric cancer patients(stage I:n = 47;stage II:n = 39;stage III:n ...     

Monocyte chemoattractant protein-1 serum levels in ovarian cancer patients.

The chemokine monocyte chemoattractant protein (MCP)-1 is an important mediator of monocyte infiltration in various solid tumours of epithelial origin. The aim of the present study was to evaluate the role of MCP-1 in the natural history of ovarian cancer and to determine its value as differentiation marker and prognostic marker regarding disease free and overall survival. This retrospective study comprises 86 patients with ovarian cancer, 48 with primary ovarian cancer and 38 with recurrent ovarian cancer, 67 patients with benign ovarian cysts and 42 healthy women. Median serum levels in patients with primary ovarian cancer, recurrent ovarian cancer, benign ovarian cysts and in healthy women were 535.6 (range 129.6-1200) pg ml(-1), 427.3 (range 193.4-1101) pg ml(-1), 371.2 (range 222-986.8) pg ml(-1) and 318.7 (range 241.3-681.4) pg ml(-1) respectively (Mann-Whitney U-test, P < 0.001). Univariate logistic regression models revealed a significant influence of MCP-1 serum levels on the odds of presenting with primary ovarian cancer versus benign cysts and versus healthy women respectively (univariate logistic regression, P < 0.001 and P < 0.001 respectively). In a multivariate logistic regression model considering MCP-1 and CA 125 serum levels simultaneously, both MCP-1 and CA 125 revealed statistical significance on the odds of presenting with primary ovarian cancer versus benign cysts (multivariate logistic regression, P = 0.05 and P < 0.001 respectively). In ovarian cancer patients, MCP-1 serum levels showed a statistically significant correlation with histological grade (Mann-Whitney U-test, P = 0.02) and age at the time of diagnosis (Mann-Whitney U-test, P = 0.03). Elevated MCP-1 serum levels prior to therapy were not associated with disease-free and overall survival (log-rank test, P = 0.2 and P = 0.7 respectively). In summary these data indicate that MCP-1 might play a functional role in the natural history of ovarian cancer and might serve as differentiation marker between benign ovarian cysts and ovarian cancer, providing additional information to the established tumour marker CA 125.     

Identification of Cisplatin-Resistance Associated Genes through Proteomic Analysis of Human Ovarian Cancer Cells and a Cisplatin-resistant Subline

Chemoresistance to cancer therapy is a major obstacle to the effective treatment of human cancers withcisplatin (DDP), but the mechanisms of cisplatin-resistance are not clear. In this study, we established a cisplatinresistanthuman ovarian cancer cell line (COC1/DDP) and identified differentially expressed proteins related tocisplatin resistance. The proteomic expression profiles in COC1 before and after DDP treatment were examinedusing 2-dimensional electrophoresis technology. Differentially expressed proteins were identified using matrixassistedlaser desorption/ ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and high performanceliquid chromatography-electrospray tandem MS (NanoUPLC-ESI-MS/MS). 5 protein spots, for cytokeratin 9,keratin 1, deoxyuridine triphosphatase (dUTPase), aarF domain containing kinase 4 (ADCK 4) and cofilin1,were identified to be significantly changed in COC1/DDP compared with its parental cells. The expression ofthese five proteins was further validated by quantitative PCR and Western blotting, confirming the results ofproteomic analysis. Further research on these proteins may help to identify novel resistant biomarkers or revealthe mechanism of cisplatin-resistance in human ovarian cancers.     

LncRNA ZEB2-AS1在卵巢癌组织中的表达水平及临床病理特征与预后的关系

目的:探讨长链非编码核糖核酸（LncRNA）锌指E盒结合同源盒蛋白2-AS1（LncRNA ZEB2-AS1）在卵巢癌组织中的表达水平，并分析其与患者临床病理特征及预后的关系。方法:收集2015年3月至2016年3月本院收治的卵巢癌患者90例为卵巢癌组，同时选取同期于本院体检的健康志愿者52例为对照组。实时荧光定量聚合酶链反应(qRT-PCR)检测LncRNA ZEB2-AS1表达水平。收集患者临床病理资料，根据LncRNA ZEB2-AS1表达水平检测结果将其分为高表达组（52例）与低表达组（38例），分析其与患者临床病理特征关系。对卵巢癌患者随访3年，采用Kaplan-Meier法分析LncRNA ZEB2-AS1表达与患者预后关系。采用Cox比例风险模型分析影响卵巢癌患者预后的相关因素。结果:卵巢癌患者血清LncRNA ZEB2-AS1表达水平显著高于对照组（P<0.05）；LncRNA ZEB2-AS1表达水平与卵巢癌患者是否发生淋巴结转移、FIGO分期、分化程度及CA125水平明显相关（P<0.05）；Kaplan-Meier法分析显示LncRNA ZEB2-AS1高表达组患者3年无疾病进展生存率与总生存率分别为25.00%、46.88%，LncRNA ZEB2-AS1低表达组患者PFS与OS均显著低于低表达组（P<0.05）；Cox多因素分析显示淋巴结转移、FIGO分期、LncRNA ZEB2-AS1表达均是影响卵巢癌患者预后的独立危险因素（P<0.05）。结论:卵巢癌患者血清LncRNA ZEB2-AS1表达水平明显升高，且与患者临床病理特征及预后密切相关，可能作为卵巢癌早期诊断的标记物及治疗靶点。     

Serum folate receptor alpha as a biomarker for ovarian cancer: Implications for diagnosis,prognosis and predicting its local tumor expression

Folate receptor alpha (FRA) is a GPI‐anchored glycoprotein and encoded by the FOLR1 gene. High expression of FRA is observed in specific malignant tumors of epithelial origin, including ovarian cancer, but exhibits very limited normal tissue expression, making it as an attractive target for the ovarian cancer therapy. FRA is known to shed from the cell surface into the circulation which allows for its measurement in the serum of patients. Recently, methods to detect the soluble form of FRA have been developed and serum FRA (sFRA) is considered a highly promising biomarker for ovarian cancer. We prospectively investigated the levels of sFRA in patients clinically suspected of having malignant ovarian tumors. A total of 231 patients were enrolled in this study and analyzed for sFRA as well as tumor expression of FRA by immunohistochemistry. High sFRA was predominantly observed in epithelial ovarian cancer patients, but not in patients with benign or borderline gynecological disease or metastatic ovarian tumors from advanced colorectal cancers. Levels of sFRA were highly correlated to clinical stage, tumor grade and histological type and demonstrated superior accuracy for the detection of ovarian cancer than did serum CA125. High sFRA was significantly associated with shorter progression‐free survival in both early and advanced ovarian cancer patients. Finally, tumor FRA expression status was strongly correlated with sFRA levels. Taken together, these data suggest that sFRA might be a useful noninvasive serum biomarkers for future clinical trials assessing FRA‐targeted therapy.