超声造影定量参数联合癌胚抗原、中性粒细胞/淋巴细胞比值对乳腺癌改良根治术后复发转移的预测价值

摘要 目的：探讨超声造影定量参数联合癌胚抗原（CEA）、中性粒细胞/淋巴细胞比值（NLR）对乳腺癌改良根治术后复发转移的预测价值。方法：选择2020年12月至2022年1月我院收治的120例行改良根治术治疗的乳腺癌患者,所有患者均行乳腺超声造影检查获得超声造影特征图像及超声造影定量参数,检测血清CEA水平和NLR,统计术后复发转移的发生情况。受试者工作特征（ROC）曲线分析超声造影定量参数联合CEA、NLR预测乳腺癌改良根治术后复发转移的价值。结果：两组术前超声造影特征比较,复发转移组增强强度略高,大部分为高增强或整体增强,造影剂分布尚均匀。18例术后发生复发转移（复发转移组）,复发转移组峰值强度（PI）大于未复发转移组,血清CEA水平和NLR高于未复发转移组,达峰时间（TTP）小于未复发转移组（P＜0.05）。PI、TTP、CEA、NLR预测乳腺癌改良根治术后复发转移的曲线下面积（AUC）为0.693、0.764、0.763、0.781,联合PI、TTP、CEA和NLR预测乳腺癌改良根治术后复发转移的AUC为0.909,大于各指标单独预测。结论：乳腺癌改良根治术后复发转移患者超声造影参数PI增大、TTP降低,血清CEA和NLR增高,联合检测TTP、PI、CEA和NLR在乳腺癌改良根治术后复发转移中具有较高的预测价值。     

胃癌血清的表面增强拉曼光谱研究

表面增强拉曼光谱技术在癌症诊断领域已经有了广泛的研究和应用,本文利用金纳米溶胶为增强基底,采用便携式近红外拉曼光谱系统,对89例胃癌患者及正常人血清样本进行了SERS光谱探测。结果表明,血清的特征峰主要归属于氨基酸,其次是核酸、糖类及脂类。相比于正常人血清SERS光谱,胃癌血清中归属于核酸的特征峰强度都较高,大部分归属于蛋白质的特征峰强度较低,与医学研究结论相符。说明SERS技术可以有效地反映胃癌患者和正常人血清的差异,为后期SERS技术快速诊断胃癌提供了实验基础。     

利用PCA-LDA和参数-CART方法对直肠癌血清拉曼光谱的分析

本文利用拉曼光谱技术检测由直肠癌的发生导致的血清成分的变化。比较了直肠癌患者和对照组之间血清拉曼光谱的差异,并对术后直肠癌患者血清拉曼光谱的变化也进行了比较,以监测术后治疗效果。结果表明在某些波数位置不同组的拉曼峰有统计学意义的变化,这些变化反应了血清中相应的生物物质的改变。之后,主成分分析(PCA)及峰强比参数这两种方法被用于原始拉曼光谱的特征变量的提取。将线性判别分析(LDA)和分类回归树(CART)两种判别分析法用于特征变量的判别分析。PCA-LDA和参数-CART方法的诊断准确率分别为87%和90%。     

增强CT图像纹理参数联合血清CEA、CA724在食管癌术后复发转移中的临床应用价值

摘要 目的：研究增强计算机断层扫描（CT）图像纹理参数联合血清癌胚抗原（CEA）、糖类抗原724（CA724）在食管癌术后复发转移中的临床应用价值。方法：选取2019年6月-2021年7月于我院行手术治疗的86例食管癌患者,术前检测其血清CEA、CA724水平,并行增强CT扫描,将其动、静脉期图像数据行纹理分析,记录均值、中位数、标准差、不均匀度、偏度、峰度、熵值等参数。术后对86例食管癌患者进行12个月随访,根据其是否发生复发转移分为复发转移组（32例）与无复发转移组（54例）,比较两组增强CT图像纹理参数及血清CEA、CA724水平差异;采用受试者工作特征（ROC）曲线分析增强CT图像纹理参数联合血清CEA、CA724对食管癌患者术后复发转移的预测价值。结果：复发转移组动脉期熵值高于无复发转移组（P＜0.05）;复发转移组静脉期不均匀度、熵值均高于无复发转移组（P＜0.05）。复发转移组血清CEA、CA724水平高于无复发转移组（P＜0.05）。ROC曲线显示,血清CEA、CA724联合动脉期熵值及静脉期不均匀度、熵值的曲线下面积（AUC）、敏感度、特异度均较各指标单独应用有明显提升,联合应用的预测效能更高。结论：血清CEA、CA724水平和动脉期熵值及静脉期不均匀度、熵值升高与食管癌患者术后发生复发转移有关,动脉期熵值及静脉期不均匀度、熵值联合血清CEA、CA724在预测食管癌患者术后发生复发转移中的应用价值较高。     

食道癌组织表面增强拉曼光谱研究

本研究采用以金纳米粒子为增强基底的表面增强拉曼光谱技术对31位食道癌患者的62例食道组织样本进行分析,其中包含31例肿瘤组织与31例正常组织.食道癌组织和正常组织表面增强拉曼光谱之间存在明显差异.利用主成分分析和线性判别分析算法对采集的组织表面增强拉曼光谱进行诊断研究.利用主成分分析-线性判别分析统计分析方法得到诊断灵敏度与特异性分别为90.3%与90.3%.为验证所构建的主成分分析-线性判别分析算法的有效性,利用受试样品的工作特征曲线方法,对所构建的算法的有效性进行评价.通过对组织表面增强拉曼光谱谱峰归属分析可知,癌组织中蛋白质结构可能发生变化,磷脂质的相对含量下降;而氨基化合物、组蛋白、苯基丙氨酸和酪氨酸的相对含量出现上升.研究表明,以金纳米粒子为增强基底的表面增强拉曼光谱技术结合主成分分析-线性判别分析统计分析方法能够准确区分食道癌患者肿瘤与正常组织.食道癌组织表面增强拉曼光谱技术有望成为一种食道癌的临床诊断与筛查工具.     

乳腺癌改良根治术患者术后复发转移的危险因素及血清CA125、COX-2、sTNFR-P55的预测价值研究

摘要 目的：探讨乳腺癌改良根治术患者术后复发转移的危险因素及血清糖类抗原125（CA125）、环加氧酶-2（COX-2）、可溶性肿瘤坏死因子受体P55（sTNFR-P55）的预测价值。方法：对2014年1月至2016年12月新疆医科大学第一附属医院收治的109例行乳腺癌改良根治术的乳腺癌患者进行前瞻性研究,所有患者术后均随访5年,其中2例失访,107例完成随访。根据5年内患者复发转移情况将其分为复发转移组（n=31）和未复发转移组（n=76）。收集患者入院时的临床病理资料,采用电化学发光法检测术前血清CA125,采用酶联免疫吸附法检测术前血清COX-2、sTNFR-P55。采用logistic回归模型分析患者术后复发转移的影响因素,绘制受试者工作特征（ROC）曲线评估血清CA125、COX-2、sTNFR-P55对术后复发转移的预测价值。结果：复发转移组肿瘤直径＞5 cm、浸润性非特殊癌、脉管癌栓、雌激素受体（ER）/孕激素受体（PR）阴性、无内分泌治疗构成比、TNM分期IIIA期、腋窝淋巴结转移数量4~9个构成比高于未复发转移组（P<0.05）。复发转移组血清CA125、COX-2、sTNFR-P55水平高于未复发转移组（P<0.05）。多因素logistic回归分析结果显示,肿瘤直径＞5 cm、浸润性非特殊癌、TNM分期IIIA期、脉管癌栓、腋窝淋巴结转移数量4~9个、CA125升高、COX-2升高、sTNFR-P55升高是乳腺癌改良根治术患者术后5年内复发转移的独立危险因素（OR=1.318、1.213、1.223、1.137、1.257、1.241、1.313、1.351,P<0.05）。血清CA125、COX-2、sTNFR-P55均可有效预测乳腺癌术后复发转移,曲线下面积（AUC）分别为0.803、0.749、0.761,三指标联合预测术后复发转移的AUC为0.915,灵敏度和特异度分别为0.94、0.83。结论：肿瘤直径、浸润性非特殊癌、TNM分期、脉管癌栓、腋窝淋巴结转移数量以及术前血清CA125、COX-2、sTNFR-P55异常升高是乳腺癌改良根治术患者术后5年内复发转移的危险因素,术前血清CA125、COX-2、sTNFR-P55联合检测可预测乳腺癌改良根治术后的复发转移风险。     

卵巢癌患者血清的拉曼光谱研究初探

目的:探究拉曼光谱技术应用于卵巢癌研究的可能性。方法:收集卵巢癌患者血清及健康人血清各20例,用激光共聚焦显微拉曼光谱仪进行检测。结果:两组血清的平均拉曼光谱形态和谱峰基本相似,但在约1010、1158、1283、1520、1646、2307和2661cm-17个拉曼频移附近,卵巢癌患者血清的拉曼光谱谱峰强度明显低于健康对照组,而在其余大部分波段,卵巢癌患者血清的拉曼光谱强度均高于健康对照组。结论:拉曼光谱技术可以初步区分卵巢癌及健康人血清,值得进一步研究和探讨其临床应用价值。     

基于表面增强拉曼光谱的冠心病前瞻性诊断方法研究

前期研究表明血小板衍生生长因子-BB(platelet-derived growth factor-BB,PDGF-BB)与冠心病关系密切,本文基于表面增强拉曼光谱(surface-enhanced Raman spectroscopy,SERS)方法,结合PDGF-BB拉曼频移为1 509 cm~(-1)的拉曼特征峰,对60例冠心病患者,其中包括20例行皮冠状动脉介入治疗术(percutaneous coronary intervention,PCI)病人与40例未行PCI病人的尿液样本以及18例健康人尿液样本进行分析。结果显示:行PCI病人的尿液样本SERS光谱中可以检测到1 509 cm~(-1)的拉曼特征峰;而在健康人与大多数未行PCI病人的尿液SERS光谱中则检测不到。与临床资料对比发现,尿液SERS光谱与冠状动脉造影技术在判断心血管堵塞程度是否达到70%以上吻合度较高。基于表面增强拉曼光谱的冠心病检测方法有望发展为一种无创的冠心病前瞻性诊断工具,对于冠心病疑似病例是否需要行PCI提供可靠的临床诊断依据。     

药物对基于SERS技术的尿液中PDGF-BB检测影响研究

本文旨在研究基于表面增强拉曼光谱(SERS)技术检测尿液中血小板衍生生长因子(PDGF-BB)从而对冠状动脉堵塞程度进行快速无损诊断的方法是否同样适用于长期服用药物(阿司匹林、瑞舒伐他汀或硫酸氢氯吡格雷)的冠心病患者或行经皮冠状动脉介入手术(PCI术)后病人的冠状动脉堵塞程度检测。首先基于该方法对13例长期服用药物(阿司匹林、瑞舒伐他汀或硫酸氢氯吡格雷)的冠心病患者和13例行PCI术后病人的尿液样本进行检测,发现其SERS光谱中均无PDGF-BB位于1 509 cm^-1的拉曼特征峰。然后进一步分析PDGFBB水溶液与三种药物的SERS光谱,也均未发现1 509 cm^-1的拉曼特征峰。结果表明,这三种药物均对PDGFBB的SERS信号产生了影响,可见该方法并不适用于长期服用药物的冠心病患者或行PCI病人术后的冠状动脉堵塞程度的检测。     

表面增强拉曼散射技术无标记检测乳腺癌细胞来源外泌体

外泌体含有释放细胞的特异性物质,反映了释放细胞的组成成分,成为液体活检的重要物质。为了鉴别正常乳腺上皮细胞和乳腺癌细胞来源的外泌体,本研究采用表面增强拉曼(SERS)技术检测乳腺癌细胞MCF-7和人正常乳腺上皮细胞MCF-10A来源的外泌体,并且对比两种细胞外泌体的SERS光谱,筛选出相应的特征拉曼光谱。结果发现在800~1800 cm-1区域内,相对MCF-10A细胞,MCF-7来源的外泌体中归属于核酸的拉曼峰相对强度明显增高,且部分脂类峰强有所降低或部分特征峰消失,同时发现MCF-7还表现出其自己独特的拉曼谱型。此结果表明SERS技术可高灵敏度检测不同细胞来源的外泌体细微分子变化,可区分肿瘤细胞来源的外泌体与正常细胞来源的外泌体。SERS技术可作为癌症的早期检测和诊断的一种快速、无标记和无损的方法。     

Surface‐enhanced Raman scattering analysis of serum albumin via adsorption‐exfoliation on hydroxyapatite nanoparticles for noninvasive cancers screening

Combining serum albumin via adsorption‐exfoliation on hydroxyapatite particles (HAp) with surface‐enhanced Raman scattering (SERS), we developed a novel quantitative analysis of albumin method from blood serum for cancers screening applications. The quantitatively analysis obtained by our HAp method had a good linear relationship from 1 to 10 g/dL, and the lower limit of detection was less than the albumin prognostic factor for disease (3.5 g/dL). Serum albumin was adsorbed and exfoliated by HAp from serum samples of liver cancer patients, breast cancer patients and healthy volunteers and mixed with silver colloids to perform SERS spectral analysis. Based on the PLS‐SVM algorithm, the diagnostic accuracies of liver cancer patients and breast cancer patients were 100% and 96.68%, respectively. Moreover, this algorithm successfully predicted the unidentified subjects with a diagnostic accuracy of 93.75%. This exploratory work demonstrated that HAp‐adsorbed‐exfoliated serum proteins combined with SERS spectroscopy has great potential for cancer screening.     

乳腺癌术后医院感染患者病原菌分布和危险因素及血清炎症因子水平分析

目的分析乳腺癌术后医院感染患者病原菌分布、危险因素及血清炎症因子水平,并探讨其临床意义。方法收集2016年3月至2018年3月我院诊治的80例乳腺癌术后医院感染患者为观察组。同期选取80例乳腺癌术后未发生感染者为对照组。利用全自动微生物分析仪对感染患者进行病原菌分布检测。对乳腺癌术后医院感染的危险因素进行单因素回归分析,同时检测并比较两组患者血清中白细胞介素-10(IL-10)、干扰素-γ(IFN-γ)及肿瘤坏死因子-α(TNF-α)的水平。结果80例乳腺癌术后医院感染患者共检出病原微生物97株。其中革兰阴性菌55株,以大肠埃希菌及铜绿假单胞菌为主;革兰阳性菌39株,以金黄色葡萄球菌为主(16株);真菌3株。观察组患者血清中IL-10、INF-γ及TNF-α水平均显著高于对照组(均P<0.05)。患者合并疾病情况、引流天数、住院天数及辅助化疗均与乳腺癌术后发生医院感染有密切联系(均P<0.05)。结论乳腺癌术后医院感染病原菌分布较广,以革兰阴性菌为主。患者合并疾病情况、引流天数、住院天数及辅助化疗均为医院感染的危险因素。血清中炎症因子水平可作为乳腺癌术后医院感染的诊断标志物。     

Serum prolactin responses to TRH in recurrent breast cancer patients.

The response of serum prolactin (PRL) to thyrotropin-releasing hormone (TRH) was evaluated by radioimmunoassay in 6 normal women and 44 breast cancer cases. They were divided into the following 5 groups: group 1:6 normal women; group 2:10 preoperative patients with early breast cancer; group 3:13 preoperative patients with advanced cancer; group 4:13 postoperative patients with no recurrence of cancer for more than 2 years; group 5:8 postoperative patients with cancer recurrence. The maximum increment of serum PRL levels following the administration of TRH was significantly higher in groups 2, 3 and 5 than in groups 1 and 4. These results indicate that patients with recurrent breast cancer have a higher PRL response to TRH than those without recurrence of cancer.     

A novel urine analysis technique combining affinity chromatography with Au nanoparticle based surface enhanced Raman spectroscopy for potential applications in non‐invasive cancer screening

Modified nucleoside in urine samples is one of the most common biomarkers for cancer screening. Therefore, we developed a novel detection method for modified nucleoside detection in human urine. In this work, the modified nucleoside from real cancer patient's urine samples was first separated and purified using the affinity chromatography (AC) technology relying on its specific adsorption capacity. Then, surface‐enhanced Raman spectroscopy (SERS) technology with the capability of single molecular detection was used to sensitively characterize the biomolecular features of modified nucleoside. A total of 141 high‐quality SERS spectra of urinary modified nucleoside can be obtained from 50 gastric cancer patients and 43 breast cancer patients, as well as 48 healthy volunteers. Using principal component analysis combined with linear discriminant analysis (PCA‐LDA), the diagnostic sensitivities for identifying gastric cancer vs normal, breast cancer vs normal, gastric cancer vs breast cancer were 84.0%, 76.7% and 82.0%, respectively, and the corresponding diagnostic specificities for each combination were 95.8%, 87.5% and 90.7%, respectively. These results show that this novel method based on urinary modified nucleoside detection combining AC and SERS technologies holds promising potential for developing a specific, non‐invasive and label‐free tool for cancer screening.      

Parallel assessment of circulatory cell-free DNA by PCR and nucleosomes by ELISA in breast tumors

OBJECTIVES: In order to assess the potential biomolecules for breast cancer, we analyzed in parallel the levels of cell-free glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and cell-free nucleosomes in serum samples from patients with benign and malignant breast tumors. The levels of cell-free DNA obtained by quantitative PCR were compared with those obtained by enzyme-linked immunosorbent assay (ELISA). METHODS: Twenty-three patients with benign breast tumors, 27 patients with breast cancer, and 32 age-matched healthy women were recruited. The amounts of serum nucleosomes were analyzed by ELISA and the levels of cell-free GAPDH were measured by real-time quantitative PCR. The correlation between nucleosome and cell-free GAPDH levels was examined using the Spearman rank test. RESULTS: The levels of cell-free GAPDH were significantly higher in the serum samples of patients with benign and malignant breast tumors than in those of the control group (median 37,966 GE/mL, range 3,802-130,104 versus 11,770 GE/mL, range 2,198-73,522, p=0.035 and median 40,698 GE/mL, range 3,644-192,482 versus 11,770 GE/mL range 2,198-73,522, p=0.001). The concentration of cell-free GAPDH correlated significantly with the quantities of nucleosomes in serum samples (r=0.451, p=0.000). There was, however, no significant difference between healthy individuals and women with benign breast tumors or breast cancer in terms of nucleosomes determined by ELISA. CONCLUSION: Our data suggest that the cell-free serum GAPDH DNA assayed by quantitative PCR is a better biomarker than nucleosomes assayed by ELISA in patients with breast tumors.     

Use of serological proteomic methods to find biomarkers associated with breast cancer

New technologies for the detection and therapy of early stage breast cancer are urgently needed. Pathological changes in breast might be reflected in proteomic patterns in serum. A proteomic tool was used to identify proteomic patterns in serum that distinguishes neoplastic from non-neoplastic disease within the breast. Preliminary results derived from the serum analysis from 54 unaffected women and 76 patients with breast cancer were analyzed by two-dimensional (2-D) electrophoresis and matrix-assisted laser desorption/ionization-time of flight mass spectrometry, HSP27 was found up-regulated while 14-3-3 sigma was down-regulated in the serum of breast cancer patients. The two protein biomarkers were then used to classify an independent set of 104 masked serum samples. The results showed that the protein pattern on 2-D gels can completely segregate the serum of breast cancer from non-cancer. The discriminatory pattern correctly identified all 69 breast cancer cases in the masked set. Of the 35 cases of non-malignant disease, 34 were recognized as non-cancer. These findings justify a prospective population-based assessment of proteomic technology as a screening or diagnostic tool for breast cancer in high-risk and general populations. These two protein biomarkers could also be used as targets for further study in drug design and breast cancer therapy.     

血清HE4、VEGF、MCP-1及CCL20与乳腺癌患者保乳术后局部复发的关系研究

摘要 目的：探讨血清人附睾蛋白4（HE4）、血管内皮生长因子（VEGF）、单核细胞趋化因子-1（MCP-1）及CC趋化因子配体20（CCL20）与乳腺癌患者保乳术后局部复发的关系。方法：选择2015年7月~2018年7月期间本院收治的乳腺癌患者312例作为研究对象,均符合保乳术手术指征,成功实施乳腺癌保乳术,所有患者均随访3年。检测两组血清HE4、VEGF、MCP-1、CCL20水平情况,单因素及多因素Logistic回归分析影响术后局部复发的因素。使用受试者工作特征（ROC）曲线分析HE4、VEGF、MCP-1、CCL20水平单独及联合检测对保乳术后局部复发的预测价值。结果：随访过程中失访6例,剩余的306例患者根据随访结果,分为局部复发组27例、无局部复发组279例,局部复发率为8.82%。局部复发组的血清HE4、VEGF、MCP-1、CCL20水平均高于无局部复发组（P<0.05）。单因素分析结果显示,乳腺癌患者保乳术后局部复发与年龄、淋巴结转移、切缘状态、人表皮生长因子受体2（Her-2）、细胞增殖相关抗原（Ki-67）、术后规范化疗、术后足程放疗有关（P<0.05）。多因素Logistic回归分析结果显示术后规范化疗、年龄偏高、术后足程放疗是保乳术后局部复发的保护因素,HE4、VEGF、MCP-1、CCL20水平偏高,切缘状态、Her-2、Ki-67阳性以及淋巴结转移是保乳术后局部复发的危险因素（P<0.05）。HE4、VEGF、MCP-1、CCL20联合应用预测乳腺癌患者保乳术后局部复发的效能高于单一指标应用。结论：乳腺癌保乳术后局部复发患者体内HE4、VEGF、MCP-1、CCL20水平高表达,四指标联合检测可辅助预测保乳术后局部复发。且乳腺癌患者保乳术后复发还受到切缘状态、Her-2、Ki-67等多种因素的影响。     

Identification of novel serum peptides biomarkers for female breast cancer patients in Western China

This study aimed to identify novel serum peptides biomarkers for female breast cancer (BC) patients. We analyzed the serum proteomic profiling of 247 serum samples from 96 BC patients, 48 additional paired pre‐ and postoperative BC patients, 39 fibroadenoma patients as benign disease controls, and 64 healthy controls, using magnetic‐bead‐based separation followed by MALDI‐TOF MS. ClinProTools software identified 78 m/z peaks that differed among all analyzed groups, ten peaks were significantly different (P < 0.0001), with Peaks 1–6 upregulated and Peaks 7–10 downregulated in BC. Moreover, three peaks of ten (Peak 1, m/z: 2660.11; Peak 2, m/z: 1061.09; Peak 10, m/z: 1041.25) showed a tendency to return to healthy control values after surgery. And these three peptide biomarkers were identified as FGA605‐629, ITIH4 347–356, and APOA2 43–52. Methods used in this study could generate serum peptidome profiles of BC, and provide a new approach to identify potential biomarkers for diagnosis as well as prognosis of this malignancy.     

Circulating miR-19a and miR-205 in Serum May Predict the Sensitivity of Luminal A Subtype of Breast Cancer Patients to Neoadjuvant Chemotherapy with Epirubicin Plus Paclitaxel

Background

The luminal A subtype of breast cancer has a good prognosis and is sensitive to endocrine therapy but is less sensitive to chemotherapy. It is necessary to identify biomarkers to predict chemosensitivity and avoid over-treatment. We hypothesized that miRNAs in the serum might be associated with chemosensitivity.

Methods

Sixty-eight breast cancer patients received neoadjuvant chemotherapy with epirubicin plus paclitaxel. The serum of the patients was collected before chemotherapy and stored at −80°C. The samples were classified into two groups in term of the chemosensitivity. We identified the differential expression patterns of miRNAs between the chemotherapy sensitive and resistant groups using microRNA profiling. Four miRNAs that were differentially expressed between the two groups were further validated in another 56 samples. We created a model fitting formula and a receiver operating characteristics (ROC) curve using logistic regression analysis to evaluate the prediction potency.

Results

We identified 8 miRNAs differentially expressed between the two groups: 6 miRNAs were up-regulated, and 2 miRNAs were down-regulated in the resistant group compared with the sensitive group. The expression of miR-19a and miR-205 were determined to have significant differences between the two groups (P<0.05). A predictive model of these two miRNAs was created by the logistic regression analysis. The probability of this model was 89.71%. Based on the ROC curve, the specificity was 75.00%, and the sensitivity was 81.25%.

Conclusions

The combination of miR-19a and miR-205 in the serum may predict the chemosensitivity of luminal A subtype of breast cancer to epirubicin plus paclitaxel neoadjuvant chemotherapy.     

基于基因差异表达的微弱信号识别疾病相关功能

当两组样本间基因表达的差异程度较低或样本量较少时,采用通常的错误发现率(falsediscovery rate,FDR)控制水平(如5%或10%),可能无法识别足够多的差异表达基因以进行后续的功能富集分析。然而,功能富集分析对差异表达基因中的错误发现具有一定的稳健性。所以,采用较低的FDR控制水平(即允许较高的FDR)识别差异表达基因,可能可以可靠地发现疾病相关功能。本文分析了5套研究乳腺癌转移的基因表达谱,通过其中差异表达信号较强的3套数据,论证了即使差异表达基因的FDR达到25%,功能富集分析的结果仍具有较高的稳健性。然后,在另外2套差异表达信号微弱的数据中,采用25%的FDR控制水平筛选差异表达基因来进行功能富集分析,并与前述3套数据的功能富集结果做比较。结果显示,采用较低的FDR控制水平筛选差异表达基因,仍然可以可靠地识别乳腺癌转移相关功能。分析结果也提示,在乳腺癌转移过程中,一些功能较为宽泛的生物学过程(如细胞分裂、细胞周期和DNA复制等)整体受到了扰动,反映出乳腺癌转移是一种涉及广泛基因表达改变的系统性疾病。