ELISA定量分析尿液BLCA-1/-4水平诊断膀胱癌的临床价值分析

目的:探讨膀胱癌患者尿液膀胱特异性核基质蛋白(bladder cancer specific nuclear matrix proteins,BLCA)-1/-4水平及其临床应用价值。方法:本研究纳入38例膀胱癌患者、40例正常对照组。采集受试者尿液样本,通过竞争性酶联免疫吸附法(enzymelinked immunosorbent assay,ELISA)定量分析尿液中BLCA-1和BLCA-4的水平,绘制受试者工作曲线,确定cut-off值。结果:膀胱癌患者尿液BLCA-1/-4水平均显著高于对照组(P0.001);当cut-off值取0.859 ng/mL时,BLCA-1诊断膀胱癌的敏感性和特异性分别为71%(27/38)、90%(36/40)。肌层浸润性膀胱癌患者尿液BLCA-1较非肌层浸润性膀胱癌患者水平显著升高(P0.001),但不同分级膀胱癌患者尿液BLCA-4水平无显著差异(P0.05)。高级别膀胱癌患者尿液BLCA-4水平较低级别膀胱癌患者显著升高(P0.05),但不同分期膀胱癌患者尿液BLCA-4水平无显著差异(P0.05)。以cut-off为0.859 ng/mL时,BLCA-1诊断膀胱癌的敏感性和特异性分别为71%(27/38)、90%(36/40)。以cut-off为0.620 ng/mL时,BLCA-4诊断膀胱癌的敏感性和特异性分别为76.3%(29/38)、97.5%(39/40)。联合检测尿液BLCA-1和BLCA-4诊断膀胱癌的敏感性和特异性分别为84.2%(32/38)和100%(40/40),准确度为0.923(77/78),阳性预测值为100%(32/32),阴性预测值为86.9%(40/46)以及YOUDEN指数分别为0.842。结论:膀胱癌患者尿液BLCA-1和BLCA-4水平显著升高,且敏感性和特异性均较高。联合检测尿液BLCA-1和BLCA-4较单一检测用于诊断膀胱癌的临床应用价值更高。     

Tumor markers (CEA, TPA and CA 19-9) in urine of bladder cancer patients

This study was carried out to evaluate the usefulness of determining urinary levels of carcinoembryogenic antigen (CEA), tissue-polypeptide antigen (TPA), and gastro-intestinal cancer antigen (Ca19-9) in addition to the usual diagnostic procedures for bladder cancer. Sixty-seven patients with transitional bladder cancer, 40 healthy controls and 20 patients with inflammatory diseases of the urinary tract were considered. All urine samples were obtained from patients with intact renal function and no urinary tract infection. TPA and Ca19-9 urinary levels in patients with G3 bladder tumors were significantly higher than in those with lower graded neoplasms. The sensitivity, specificity, and predictive value of a positive (PV+) or negative (PV-) test and the diagnostic accuracy were also evaluated. Ca19-9 was the best urinary marker for bladder cancer (sensitivity 71.6%, specificity 91.6%, PV+ 90.5%, PV- 74.3%, diagnostic accuracy 81%).     

Levels of tissue inhibitor of metalloproteinases 1 in plasma and urine from patients with bladder cancer

AIM: To assess the potential use of plasma and urine levels of tissue inhibitor of metalloproteinases 1 (TIMP-1) in urothelial cancer. METHODS: TIMP-1 levels were determined in urine and plasma from healthy donors (n=26), patients with bacterial bladder infection (n=24), urothelial bladder adenoma (n=3) or adenocarcinoma (n=7). RESULTS: Free and total TIMP-1 in plasma were weakly but significantly correlated with age; urinary TIMP-1 was not. A strong correlation between free and total TIMP-1 in plasma was observed, with an average ratio of 0.85. No correlation between total TIMP-1 in urine and plasma was found (p=0.55). No significant differences in free or total TIMP-1 in plasma were found between healthy individuals, patients with cystitis or bladder cancer (p=0.4). Urinary TIMP-1 levels were significantly increased in patients with cystitis (p=0.001). No apparent differences in TIMP-1 levels were found in patients with bladder cancer at different stages. CONCLUSION: Our previous observation of a weak but significant correlation between plasma TIMP-1 and age was confirmed. Likewise, an association between free and total TIMP-1 in plasma with a ratio of 0.85 was established. No correlation between plasma and urine TIMP-1 was found. Measurement of TIMP-1 in plasma and/or urine is apparently not useful for the identification of bladder cancer.     

miR-126 在膀胱癌患者尿液中的表达及临床意义

目的:探讨miR-126在膀胱癌患者尿液中的表达与临床病理特征的关系,评估miR-126的肿瘤标志物诊断价值。方法:收集48例初发膀胱尿路上皮癌患者与32例健康对照者晨尿,提取尿液总RNA,通过实时荧光定量PCR技术检测各样本中的miR-126的表达水平,并经受试者工作曲线(ROC)分析其诊断价值。结果:膀胱癌患者尿液中的miR-126表达水平相对健康对照组明显上调(P0.01),其表达水平在不同病理级别之间存在显著差异(P均0.05),且低级别组表达水平略高于高级别组,与肿瘤大小、数目以及淋巴转移也有一定的相关性(P0.05),而与患者的年龄、性别、TNM分期等均无相关性(P0.05)。通过ROC曲线分析尿液中miR-126诊断膀胱肿瘤的曲线下面积(AUC)为0.861,当最佳切点定在7.475时,miR-126诊断膀胱肿瘤的敏感性和特异性分别为75.0%、81.2%。结论:膀胱癌患者尿液中miR-126的表达差异能够反映病情进展程度,其表达水平对膀胱肿瘤的早期诊断及病情评估具有一定的价值。     

Optical sensory arrays for the detection of urinary bladder cancer‐related volatile organic compounds

Non‐invasive detection of urinary bladder cancer remains a significant challenge. Urinary volatile organic compounds (VOCs) are a promising alternative to cell‐based biomarkers. Herein, we demonstrate a novel diagnosis system based on an optic fluorescence sensor array for detecting urinary bladder cancer VOCs biomarkers. This study describes a fluorescence‐based VOCs sensor array detecting system in detail. The choice of VOCs for the initial part was based on an extensive systematic search of the literature and then followed up using urinary samples from patients with urinary bladder transitional cell carcinoma. Canonical discriminant analysis and partial least squares discriminant analysis (PLS‐DA) were employed and correctly detected 31/48 urinary bladder cancer VOC biomarkers and achieved an overall 77.75% sensitivity and 93.25% specificity by PLS‐DA modelling. All five urine samples from bladder cancer patients, and five healthy controls were successfully identified with the same sensor arrays. Overall, the experiments in this study describe a real‐time platform for non‐invasive bladder cancer diagnosis using fluorescence‐based gas‐sensor arrays. Pure VOCs and urine samples from the patients proved such a system to be promising; however, further research is required using a larger population sample.      

Free DNA in urine: a new marker for bladder cancer? Preliminary data

The aim of the present preliminary study was to investigate the presence of free DNA (FDNA) in urine as a possible marker for the diagnosis of bladder cancer. Naturally voided morning urine specimens were collected from 57 patients with suspected bladder cancer before cystoscopy. A standard urine test was performed; the specimens were then processed in order to obtain a quantitative evaluation of the presence of free DNA in the urine. Twenty-two patients were excluded from the study because they had leukocyturia and/or bacteriuria. Free DNA concentrations higher than 250 ng/mL were found in all 16 patients showing bladder cancer at cystoscopy and in seven (36.8%) of the 19 patients with negative cystoscopy. Urinary FDNA seems to have an excellent sensitivity: we observed no false negative cases and 36.8% false positive cases. By contrast, only 6.25% of the bladder cancer patients had positive urine cytology. Our results seem promising, although further studies and larger numbers are needed to define urinary free DNA as a reliable marker of bladder cancer.     

Discovery of Apo-A1 as a potential bladder cancer biomarker by urine proteomics and analysis

Bladder cancer is clinically characterized by high recurrent rate and poor prognosis and thereby patients need regular re-examinations which are invasive, unpleasant, and expensive. A noninvasive and less expensive method for detecting and monitoring bladder cancer would thus be advantageous. In this study, by using the two-dimensional electrophoresis (2-DE) approach with subsequent mass spectrometry (MS), we demonstrated the increased expression of apolipoprotein-A1 (Apo-A1) in individual urine from patients with bladder cancer, which was confirmed by Western blot results. A further analysis of the urinary Apo-A1 levels by an enzyme-linked immunosorbent assay yielded results that were consistent with the Western blot, and suggested Apo-A1 could provide diagnostic utility to distinguish patients with bladder cancer from healthy controls at 19.21 ng/ml. Further validation assay in a larger number of urine samples (n = 379) showed that Apo-A1 could be used as a biomarker to diagnosis bladder cancer with a sensitivity and specificity of 89.2% and 84.6% respectively. Moreover, the application of exfoliative urinary cytology in combination with the urine Apo-A1 detection could significantly increased the sensitivity in detecting bladder cancer. Our data showed a significant relationship of expressed Apo-A1 was established between bladder cancer and normal controls. Apo-A1 could be a potential biomarker for the diagnosis of bladder cancer.     

The biochemical value of urinary metalloproteinases 3 and 9 in diagnosis and prognosis of bladder cancer in Egypt

Background

Matrix metalloproteinases (MMPs) have long been associated with cancer-cell invasion and metastasis. Few studies are available that describe this association with bladder cancer either related or unrelated to schistosoma infection.Evaluating the urinary levels of MMP3 and MMP9 as diagnostic and prognostic biomarkers in different stages of schistosomal and non schistosomal bladder cancer was the aim of the present study.Urine samples were collected from 70 patients with schistosomal and non schistosomal bladder cancer at early and advanced stages and also from12 healthy volunteers as controls. Urinary levels of MMP-3 and MMP-9 was measured by ELISA technique. Sensitivity and specificity of both markers were determined.

Results

Urinary levels of both MMP-3 and MMP-9 were significantly elevated in all bladder cancer patients compared with controls. MMP-3 started to elevate in early stages of schistosomal bladder cancer ( 0.173 ng/ml) and non-schistosomal bladder cancer patients (0.308 ng/ml) compared to control (0.016 ng/ml) and remained elevated in advanced stages (0.166, 0.235 ng/ml) of both types of bladder cancer patients. In contrast, MMP-9 showed a significant elevation in advanced stages only of both schistosomal and non schistosomal bladder cancer patients (10.33, 21.22 ng/ml) compared to control (0.409 ng/ml) and this elevation of both markers was much higher in non schistosomal bladder cancer. Both Metalloproteinases were specific for the diagnosis of the disease but MMP-3 was more sensitive and this sensitivity was evident in the early stage (84.85% for MMP3, 27.28% for MMP9).

Conclusions

MMP3 may be the recommended urinary metalloproteinases as early diagnostic biomarker in the early stages of both types of bladder cancer although both MMP9 and MMP3 can be used in the diagnosis of advanced stages. Further studies are required on large number of urine samples to confirm these results.     

Urinary zinc excretion and zinc status of patients with Β-thalassemia major

In this study, zinc status and urinary zinc excretion with and without desferrioxamine (DFO) infusion and the relationship between urinary zinc excretion and renal tubular dysfunction in thalassemia major (TM) patients were investigated. Forty TM patients were given four DFO infusions on alternate days over a 1-wk period prior to the transfusion. On each day that DFO was given, a 24-h urine collection initiated. DFO was omitted for 1-wk before the following transfusion and during the period four 24-h urine collections were performed. Twenty healthy children provided 24-h urine collection as controls. Blood samples were taken on each of two consecutive transfusion days of the patients and from the controls. Urinary zinc excretion was measured and plasma and red blood cell (RBC) zinc analysis were performed by inductively coupled plasma-atomic emission spectrophotometry. UrinaryN-acetyl-Β-D-glucosaminidase (NAG) activity and creatinine were determined in morning urine specimens. The mean plasma zinc concentration was significantly lower in the patients not given DFO compared to the values of the patients given DFO and the control group. The mean RBC zinc concentration (Μmol/g Hb) in the patients (with and without DFO) and the control group were similar. Urinary zinc excretion was significantly higher in the patients receiving DFO compared to the control group, whereas urinary zinc excretion in the patients not given DFO was not different from the controls. Urinary NAG indices (U/g Cr) were significantly higher in the patients compared to controls. Urinary zinc excretion was correlated with the urinary NAG indices.     

Simultaneous determination of urinary CEA, ferritin and TPA in Egyptian bladder cancer patients.

Urinary carcinoembryonic antigen (CEA), ferritin (Fer) and tissue polypeptide antigen (TPA) were determined in 328 cases (106 with bladder cancer, 152 with non-malignant urinary tract disease and 70 healthy controls). CEA was determined by the kit supplied by Roche Diagnostica (CEA EIA Doumab 60), ferritin by the Tandem-E Fer kit supplied by Hybritech and TPA by the Prolifigen TPA-IRMA kit supplied by Sangtec Medical. The results of this work revealed that combined determination of urine CEA and Fer, CEA and TPA or Fer and TPA showed higher sensitivity than determination of the individual markers. There was no significant difference between combined and individual marker determination with respect to false positivity in non-malignant urinary tract diseases. At 97% specificity, the sensitivities of urine CEA, Fer and TPA were 82.1%, 71.7% and 90.6%, respectively, while combined urine CEA & Fer, CEA & TPA and Fer & TPA showed sensitivities of 92.5%, 99.1% and 98.1%, respectively. When the specificity was related to the entire non-cancer group (patients with benign urinary tract diseases and normal controls), some reduction in the sensitivities of the combined markers was noted compared to the normal group only. In conclusion, combined determination of urine markers is superior to determination of individual markers in the diagnosis of bladder cancer.     

The diagnostic accuracy of sputum and urine cytology

The diagnostic accuracies of sputum and urinary cytology were examined in series spanning more than 20 years. The sensitivity and respiratory tract cytology in 1,289 patients with subsequently proven lung cancer was 69% while that or urine cytology in 860 patients with urinary tract cancer was 77%. The specificities were 96% for lung cancer and 97% for urinary tract cancer. Neither procedure was widely used for routine screening, but diagnostic cytology played an important part in providing a definite morphologic diagnosis in many of these cases. Urinary cytology was also very effective in the follow-up of patients with treated bladder cancer because of its high sensitivity for detecting carcinoma in situ.     

Application of urinary mutagen testing to detect workplace hazardous exposure and bladder cancer

The objectives of this biochemical epidemiologic case-control study were to evaluate urinary mutagen testing for occupational exposure assessment, and for possible screening for bladder cancer in the workplace. Thirty-seven patients (19 bladder cancer cases and 18 controls) completed a questionnaire. Two urine samples, i.e. a work sample taken while at work, and a home sample, were requested from each patient. Twenty-six patients (17 cases and 9 controls) gave a total of 47 24-h urine samples for mutagenicity testing by the Ames test. A positive Ames test was found to be associated significantly with current occupation with hazardous exposure (odds ratio = 3.7, 95%CI 1.1–12.9), and non-significantly with bladder cancer (odds ratio = 1.8, 95%CI 0.5–7.1). Our results show that the urinary Ames test has the potential of being used as a surveillance for current workplace hazardous exposure (sensitivity = 52%, specificity = 77%, positive predictive value = 72%, negative predictive value = 59%, positive likelihood ratio = 2.3), but not as a screening test for bladder cancer cases (sensitivity = 42%, specificity = 71%, positive predictive value = 3%, negative predictive value = 98%, positive likelihood ratio = 1.5).     

血清LncRNA XIST与miR-33a在膀胱癌中的表达及临床意义

目的:探究血清长链非编码RNA X染色体失活特异转录本(Lnc RNA XIST)与微小RNA-33a(mi R-33a)在膀胱癌中的表达及临床意义。方法:选择2017年4月至2019年8月青岛大学附属医院诊治的95例膀胱癌患者作为膀胱癌组,选择同期体检的95例健康者作为健康组。采用荧光定量PCR检测两组的血清LncRNA XIST与mi R-33a表达水平,分析患者的临床病理参数与血清LncRNA XIST、mi R-33a表达水平的关系,采用受试者工作特征曲线(ROC)分析血清LncRNA XIST与mi R-33a对膀胱癌的预测价值。结果:与健康组相比,膀胱癌组的血清LncRNA XIST表达水平明显升高(P0.05),而血清mi R-33a表达水平明显下降(P0.05)。血清LncRNA XIST与mi R-33a表达均与膀胱癌患者的TNM分期和淋巴结转移情况相关(P0.05)。血清LncRNA XIST联合mi R-33a(AUC=0.830,敏感性=90.47%,特异性=89.85%)预测膀胱癌的临床价值明显高于血清LncRNA XIST(AUC=0.716,敏感性=81.36%,特异性=80.74%)及血清mi R-33a(AUC=0.736,敏感性=82.19%,特异性=81.09%)单独检测。结论:血清LncRNA XIST表达异常升高、血清mi R-33a表达降低与膀胱癌发生密切相关,联合检测有助于预测膀胱癌发生的风险,从而为临床制定针对性干预和治疗方案提供参考。     

Use of mailed urine specimens in diagnosing urothelial carcinoma by cytology and DNA image analysis

OBJECTIVE: To evaluate the usefulness of urine specimens collected via a mailer system and analyzed by cytology and DNA ploidy for the detection of urothelial carcinoma (UC). STUDY DESIGN: We retrospectively reviewed the diagnoses of 91 mailed urine specimens received from 72 patients, 67% of whom had a history of UC. The specimens were fixed in an equal volume of 50% ethanol solution before being mailed. The cytologic findings were interpreted in conjunction with DNA ploidy image analysis. We compared these initial diagnoses with those of follow-up examinations, including biopsies, cystoscopic findings and urinary cytology/DNA ploidy analyses. In addition, to examine the quality of the mailed samples, 3 cytopathologists performed a blinded assessment of cytologic slides of 20 mailed and 17 fresh urinary samples for bacterial overgrowth, urothelial degeneration, and presence of proteinaceous material and crystals. RESULTS: Follow-up was available for 68 of the 91 mailed specimens. The sensitivity for detecting UC using mailed urine specimens that were analyzed by both cytology and DNA ploidy was 61%, while specificity was 92%. The levels of bacterial overgrowth and urothelial degeneration in the mailed specimens were not significantly greater than in the fresh specimens (p>0.05). The levels of proteinaceous material and crystals were significantly higher in the mailed specimens (p<0.05). CONCLUSION: The results of combined cytology and DNA ploidy image analysis by using mailed urine samples were comparable to those of fresh urine specimens for the detection of UC reported in previous publications. The increase in crystals and proteinaceous material did not impede diagnostic interpretation. The mailing system is a reliable and convenient method of monitoring and triaging patients with UC or related symptoms.     

Proteomic analysis of urinary biomarker candidates for nonmuscle invasive bladder cancer

Nonmuscle invasive tumors of the bladder often recur and thereby bladder cancer patients need regular re-examinations which are invasive, unpleasant, and expensive. A noninvasive and less expensive method, e.g. a urine dipstick test, for monitoring recurrence would thus be advantageous. In this study, the complementary techniques mass spectrometry (MS) and Western blotting (WB)/dot blot (DB) were used to screen the urine samples from bladder cancer patients. High resolving MS was used to analyze and quantify the urinary proteome and 29 proteins had a significantly higher abundance (p<0.05) in bladder cancer samples compared with control urine samples. The increased abundance found in urine from bladder cancer patients compared with controls was confirmed with Western blot for four selected proteins; fibrinogen β chain precursor, apolipoprotein E, α-1-antitrypsin, and leucine-rich α-2-glycoprotein 1. Dot blot analysis of an independent urine sample set pointed out fibrinogen β chain and α-1-antitrypsin as most interesting biomarkers having sensitivity and specificity values in the range of 66-85%. Exploring the Human Protein Atlas (HPA) also revealed that bladder cancer tumors are the likely source of these proteins. They have the potential of being useful in diagnosis, monitoring of recurrence and thus may improve the treatment of bladder tumors, especially nonmuscle invasive tumors.     

Diagnosis of bladder cancer with urinary cytology, immunocytology and DNA-image-cytometry.

DNA-image-cytometry and antibodies directed against the Lewis X- and the 486p 3/12 antigen were applied to improve diagnostic accuracy of urinary cytology for the detection of bladder cancer. Cytology, immunocytology and DNA-image-cytometry were performed in spontaneously voided urine samples and barbotage bladder washings from 71 patients. The DNA content was determined using the CM-1 Cytometer according to the recommendation of the ESCAP Consensus Report on Standardization of DNA-image-cytometry (1995). For immunocytological examination we used the monoclonal anti Lewis X antibody P-12 and antibody 486p 3/12. All patients underwent subsequent cystoscopy and for any suspicious lesion biopsy or transurethral resection was done. Histological findings revealed 31 patients with transitional cell carcinomas of different stages and grades of malignancy. 40 patients had various benign diseases of the urinary bladder. Cytology yielded a sensitivity of 68% and a specificity of 100%. DNA aneuploidy was detected in 81% of cancer patients with a specificity of 100%. By combination of these two methods the overall sensitivity increased to 87%. Immunocytology with Lewis X and 486p 3/12 antibodies showed reactivity in 84% and 87% in combination with a specificity of 80% and 70%, respectively. By combining urinary cytology, immunocytology and/or DNA-image-cytometry the overall sensitivity increased to 94% with no change in specificity. DNA-image-cytometry should be used to evaluate particularly urothelial cells suspicious for malignancy in urinary specimens. Because of low specificity the monoclonal antibodies against Lewis X- and 486p 3/12 antigens are not helpful in screening for bladder cancer. Nevertheless, their high sensitivity may justify their use in case DNA image cytometry is not available and in the follow up of patients with transitional cell carcinoma.     

黑色素瘤患者血浆miR-21表达与临床病理特征的相关性

摘要 目的：探讨黑色素瘤患者血浆miR-21表达与临床病理特征的相关性。方法：2018年2月到2019年5月选择在本院诊治的黑色素瘤患者121作为黑色素瘤组,另选取同期良性皮肤肿瘤患者121例作为良性组。采集患者的空腹静脉血并提取血浆,采用qRT-PCR 技术检测血浆miR-21表达。调查患者的临床病理特征并进行相关性分析。结果：黑色素瘤组的血浆miR-21相对表达水平显著高于良性组(P<0.05)。在黑色素瘤组中,血浆miR-21相对表达水平与患者的年龄、性别、饮酒、肿瘤部位等无相关性(P>0.05),与临床分期、肿瘤转移、溃疡、吸烟等有显著相关性(P<0.05)。取miR-21诊断黑色素瘤的临界值(4.71),其诊断黑色素瘤的敏感性、特异性、准确性分别为77.6 %、87.0 %和81.7 %。logistic 回归模型分析显示吸烟、溃疡、miR-21表达水平都为影响黑色素瘤发生的重要因素(P<0.05)。结论：miR-21变化在黑色素瘤中呈现高表达,且与临床特征显著相关性,早期鉴别诊断黑色素瘤的预后效果比较好,同时有助于提高患者的生存率与生活质量。     

Multiplex PCR and Next Generation Sequencing for the Non-Invasive Detection of Bladder Cancer

Background

Highly sensitive and specific urine-based tests to detect either primary or recurrent bladder cancer have proved elusive to date. Our ever increasing knowledge of the genomic aberrations in bladder cancer should enable the development of such tests based on urinary DNA.

Methods

DNA was extracted from urine cell pellets and PCR used to amplify the regions of the TERT promoter and coding regions of FGFR3, PIK3CA, TP53, HRAS, KDM6A and RXRA which are frequently mutated in bladder cancer. The PCR products were barcoded, pooled and paired-end 2 x 250 bp sequencing performed on an Illumina MiSeq. Urinary DNA was analysed from 20 non-cancer controls, 120 primary bladder cancer patients (41 pTa, 40 pT1, 39 pT2+) and 91 bladder cancer patients post-TURBT (89 cancer-free).

Results

Despite the small quantities of DNA extracted from some urine cell pellets, 96% of the samples yielded mean read depths >500. Analysing only previously reported point mutations, TERT mutations were found in 55% of patients with bladder cancer (independent of stage), FGFR3 mutations in 30% of patients with bladder cancer, PIK3CA in 14% and TP53 mutations in 12% of patients with bladder cancer. Overall, these previously reported bladder cancer mutations were detected in 86 out of 122 bladder cancer patients (70% sensitivity) and in only 3 out of 109 patients with no detectable bladder cancer (97% specificity).

Conclusion

This simple, cost-effective approach could be used for the non-invasive surveillance of patients with non-muscle-invasive bladder cancers harbouring these mutations. The method has a low DNA input requirement and can detect low levels of mutant DNA in a large excess of normal DNA. These genes represent a minimal biomarker panel to which extra markers could be added to develop a highly sensitive diagnostic test for bladder cancer.     

子宫内膜癌患者血浆溶血磷脂酸、血清癌抗原125及人附睾蛋白4的表达及临床意义

目的:探讨子宫内膜癌患者血浆溶血磷脂酸(LPA)、血清癌抗原125(CA125)及人附睾蛋白4(HE4)的表达及与临床病理特征的关系。方法:选取2014年3月到2016年6月在同济大学附属第一妇婴保健院进行治疗的子宫内膜癌患者76例作为观察组,另选取我院同期收治的子宫内膜增生症患者50例作为良性病变组,再选取同期在我院体检结果为健康的志愿者50例作为对照组。比较三组受试者血浆LPA、血清CA125以及HE4水平。以病理检测结果为金标准,计算血浆LPA、血清CA125、HE4诊断子宫内膜癌的灵敏度、特异度、阳性预测值、阴性预测值。分析子宫内膜癌患者血浆LPA、血清CA125以及HE4水平与临床病理特征的关系。结果:观察组的血浆LPA、血清CA125以及HE4水平均高于对照组和良性病变组(P0.05),良性病变组的血浆中CA125水平高于对照组(P0.05)。血浆LPA、血清CA125以及HE4诊断子宫内膜癌的灵敏度、特异度、阳性预测值、阴性预测值比较无统计学差异(P0.05)。子宫内膜癌患者LPA水平与年龄、肿瘤直径无关(P0.05),与淋巴结转移、临床分期、分化程度、疾病类型有关(P0.05);CA125、HE4水平与年龄、疾病类型无关(P0.05),与淋巴结转移、临床分期、肿瘤直径、分化程度有关(P0.05)。结论:子宫内膜癌患者血浆LPA、血清CA125以及HE4水平偏高,LPA、CA125、HE4与部分临床病理参数相关,三指标对子宫内膜癌均有较高的诊断价值。     

Urinary cell-free DNA as a potential tumor marker for bladder cancer

The objective was to assess the possibility of measuring urine creatinine (UCr)-adjusted urinary cell-free (ucf) DNA concentration as a noninvasive screening tool for bladder cancer. Using PicoGreen-based detection, the ucf-DNA/UCr concentration was quantified in urine supernatant specimens from 46 bladder cancer patients and 98 controls and compared to 400-bp real-time PCR-based detection, which detected the amplification of 400-bp beta-actin (named 400-bp ucf-DNA/UCr). The mean concentrations for both PicoGreen and 400-bp ucf-DNA (ng/mL)/UCr (mg/dL) were significantly higher in bladder cancer patients than in controls: 15.28 vs 6.68 (p<0.001, t-test) and 14.98 vs 1.07 (p<0.001), respectively. Among different stages and grades, no significant difference was found between these two methods. The areas under the ROC curves of PicoGreen and 400-bp ucf-DNA/UCr were 0.571 (95% confidence interval, 0.451-0.692) and 0.805 (95% confidence interval, 0.713-0.896), respectively. In 400-bp ucf-DNA/UCr, the best sensitivity and specificity were 86.1% and 72.0% at the cutoff value of 0.0645. These data indicated that 400-bp ucf-DNA/UCr is more reliable for bladder cancer detection than PicoGreen. In conclusion, our results suggest that ucf-DNA/UCr can be used as a potential tumor marker for bladder cancer, especially for detecting longer DNA fragments.