骨髓增生异常综合征分子生物学预后标志研究进展

骨髓增生异常综合征(myelodysplastic syndrome MDS)是一组有着广泛临床特点和疾病转归的克隆性造血干细胞疾病。疾病危险度的评估对准确预测患者预后起着重要作用。1997年国际预后评分系统(International Prognostic Scoring System,IPSS)制定使其成为评估MDS危险度的标准工具,后续的模型在其基础上得以补充改进。最近,多个研究团队使用二代测序技术在多数MDS病人中发现了基因突变,研究证明它们有独立的预后意义,能补充完善MDS的预后模型。然而,突变信息分析复杂,目前应用到临床还有困难。尽管有诸多限制,二代测序能更准确的评估MDS病人预后,提高对MDS病人的诊疗水平,未来在临床上有更广泛的应用。本文就MDS目前的预后模型、分子生物学事件作为学术的预后标志及其优缺点进行综述。

乳腺癌磁共振动态增强扫描影像组学特征与生物学预后因子的关系

目的探讨乳腺癌磁共振动态增强扫描(DCE-MRI)影像组学特征与生物学预后因子的关系。方法选取100例乳腺癌患者,所有患者在术前均接受磁共振(MRI)平扫和增强扫描,术中收集患者肿瘤组织,术后采用免疫组织化学染色法检测肿瘤组织中增殖细胞核抗原(Ki-67)、人类表皮生长因子受体2(HER2)、缺氧诱导因子-2α(HIF-2α)阳性表达率。分析DCE-MRI影像组学特征中肿瘤形态、边缘、内部强化、时间-信号强度曲线(TIC)分型与乳腺癌组织分级、淋巴结转移、Ki-67、HER2、HIF-2α表达的关系,并比较Ki-67、HER2、HIF-2α阳性、阴性表达的乳腺癌患者3年生存情况。结果有分叶者淋巴结转移比例高于无分叶者(P﹤0.05),环形强化者低分化、淋巴结转移比例均高于其他强化方式(P﹤0.05);有分叶者Ki-67阳性率、HIF-2α阳性率均高于无分叶者(P﹤0.05),不均匀强化者HIF-2α阳性率高于其他强化方式(P﹤0.05),TIC分型Ⅱ型者Ki-67阳性率高于其他型(P﹤0.05);有分叶者出现Ki-67、HIF-2α阳性的概率分别是无分叶者的4.759、3.951倍(P﹤0.05);环形强化是肿瘤内部强化中出现HIF-2α阳性的保护因素(P﹤0.05);Ki-67、HER2、HIF-2α蛋白表达呈阳性的乳腺癌患者3年生存率均低于阴性患者(P﹤0.05)。结论乳腺癌患者DCE-MRI影像组学特征与其生物学预后因子Ki-67、HIF-2α存在一定的关系,可间接反映乳腺癌患者的预后情况。

乳腺癌自动乳腺全容积成像表现与生物学预后因子的关系

目的分析乳腺癌自动乳腺全容积成像(ABVS)表现与雌激素受体(ER)、孕激素受体(PR)、肿瘤抑制蛋白p53、雌激素诱导蛋白pS2及增殖细胞核抗原(PCNA)的关系。方法收集术前行ABVS检查的84例乳腺癌患者的临床资料,采用免疫组化染色法检测生物学预后因子ER、PR、p53、pS2及PCNA的表达情况,分析ABVS表现与ER、PR、p53、pS2及PCNA表达的关系。结果84例乳腺癌患者中,ER、PR、p53、pS2及PCNA阳性表达率分别为67.86%、60.71%、60.71%、65.48%及64.29%。肿块大小≥2 cm乳腺癌患者的PCNA阳性表达率高于肿块大小﹤2 cm的患者(P﹤0.05)。有肿块内钙化乳腺癌患者的ER、PR、p53阳性表达率均高于无肿块内钙化的患者,pS2阳性表达率低于无肿块内钙化的患者,差异均有统计学意义(P﹤0.05)。有毛刺征乳腺癌患者的ER、PR、p53、pS2及PCNA阳性表达率均高于无毛刺征的患者(P﹤0.05)。有淋巴结转移乳腺癌患者的PR阳性表达率高于无淋巴结转移的患者,p53、pS2阳性表达率均低于无淋巴结转移的患者,差异均有统计学意义(P﹤0.05)。结论ABVS表现与ER、PR、p53、pS2及PCNA的表达均具有一定的关系,对治疗方案的制订和预测预后具有一定的参考价值。

乳腺癌MRI与生物学预后因子相关性的研究现状

乳腺癌是女性最常见的恶性肿瘤之一,Ki-67、HER2/neu、ER、PR、PCNA、VEGF及MVD等生物学、组织学指标在评价乳腺癌生物学行为和预后方面的作用日益受到肯定。随着动态增强磁共振成像的广泛使用及扩散加权成像、磁共振波谱技术的发展,MRI也从单纯的形态学诊断向形态与功能并重的方向发展,在乳腺癌的早期检测、生物学评价和疗效检测、预后等方面显现优势。就乳腺癌MRI与生物学预后因子的相关性方面进行综述。

血清CYFRA21-1在非小细胞肺癌手术疗效及预后判断中的价值

目的：探讨血清肿瘤标志物CYFRA21-1在非小细胞肺癌（NSCLC）手术效果、转移复发监测中的应用价值。方法：应用免疫放射分析（IRMA）测定35例健康成人及28例不同分期（Ⅰ期4例、Ⅱ期11例、Ⅲ期9例、Ⅳ期4例）的NSCLC患者及12例术后转移复发者血清CYFRA21－1的水平。结果：35例健康成人组CYFRA21－1为（1．5～0．8）ng／ml，28例NSCLC患者CYFRA21－1为（19．2±7．5）ng／ml较健康成人组明显升高（P〈0．01）；Ⅰ－Ⅳ期术后水平较术前明显下降（P〈0．01），各期间术后水平无显著差异（P〉0．05），术后转移复发时其水平显著升高，与术前比较无显著差异（P〉0．05）。结论：血清CYFRA21－1在监测NSCLC患者手术疗效及预示其转移、复发是一项很有价值的指标。

Prognositic value of anoikis and tumor immune microenvironment-related gene in the treatment of osteosarcoma

Objective:Osteosarcoma is a highly aggressive primary malignant bone tumor commonly seen in children and adolescents,with a poor prognosis.Anchorage-dependent cell death(anoikis)has been proven to be indispensable in tumor metastasis,regulating the migration and adhesion of tumor cells at the primary site.However,as a type of programmed cell death,anoikis is rarely studied in osteosarcoma,especially in the tumor immune microenvironment.This study aims to clarify prognostic value of anoikis and tumor immune microenvironment-related gene in the treatment of osteosarcoma.Methods:Anoikis-related genes(ANRGs)were obtained from GeneCards.Clinical information and ANRGs expression profiles of osteosarcoma patients were sourced from the therapeutically applicable research to generate effective therapies and Gene Expression Omnibus(GEO)databases.ANRGs highly associated with tumor immune microenvironment were identified by the estimate package and the weighted gene coexpression network analysis(WGCNA)algorithm.Machine learning algorithms were performed to construct long-term survival predictive strategy,each sample was divided into high-risk and low-risk subgroups,which was further verified in the GEO cohort.Finally,based on single-cell RNA-seq from the GEO database,analysis was done on the function of signature genes in the osteosarcoma tumor microenvironment.Results:A total of 51 hub ANRGs closely associated with the tumor microenvironment were identified,from which 3 genes(MERTK,BNIP3,S100A8)were selected to construct the prognostic model.Significant differences in immune cell activation and immune-related signaling pathways were observed between the high-risk and low-risk groups based on tumor microenvironment analysis(all P<0.05).Additionally,characteristic genes within the osteosarcoma microenvironment were identified in regulation of intercellular crosstalk through the GAS6-MERTK signaling pathway.Conclusion:The prognostic model based on ANRGs and tumor microenvironment demonstrate good predictive power and provide more personalized treatment options for patients with osteosarcoma.

乳腺癌组织FAP表达病理生物学意义的研究

目的:探讨乳腺癌成纤维细胞活化蛋白(FAP)的表达与乳腺癌临床病理因素和生物学预后因子(ER、PR、p53、c-erbB-2、Ki-67)的相关性,评价FAP在乳腺癌的表达意义。方法:选取经病理确诊的乳腺癌患者82例,免疫组织化学法检测乳腺癌组织FAP的表达。收集乳腺癌患者的临床病理信息,分析FAP与乳腺癌临床病理因素和生物学预后因子的表达水平的关系。结果:FAP表达与患者年龄、肿瘤部位、肿瘤大小与FAP的表达无相关性(P>0.05),临床分期与FAP表达呈正相关(r=0.922,P=0.000),病理分级与FAP表达呈弱正相关,r=0.360,P=0.001。FAP表达在有无淋巴结转移组间差异统计学意义,t=11.003,P=0.00。FAP表达与p53(r=0.498,P=0.000)、c-erbB-2(r=0.326,P=0.004)、Ki-67(r=0.449,P=0.000)的表达呈正相关,FAP表达与ER、PR的表达无相关性,P>0.05。结论:FAP在女性乳腺癌发生、发展、侵袭转移方面起到了重要的作用。FAP可作为预测乳腺癌预后的重要因子。

乳腺癌患者磁共振扩散加权成像感兴趣区的选择与生物预后因子的相关性分析

目的评价磁共振扩散加权成像(DWI)中感兴趣区(ROI)的三种不同选择与乳腺癌生物预后影响因子的相关性及其应用价值。方法回顾性分析经手术并病理诊断为乳腺癌的82例患者资料。根据术后病理证实将乳腺癌分为雌激素受体(ER)阳性组及阴性组、孕激素受体(PR)阳性组及阴性组、人表皮生长因子受体-2(HER-2)阳性组及阴性组。两名高低年资放射医师独立在乳腺DWI图像中选取三种不同ROI法(小ROI、面积ROI、容积ROI)测量病灶的表观扩散系数(ADC)值。结果三种选取ROI方法所测得的ADC值可重复性均较高,组内相关系数(ICC)>0.90。三种测量方法的ADC值在PR及ER阳性及阴性组之间有差异,ER、PR阳性组的ADC低于阴性组。三种测量方法测得的ADC值在HER-2阳性组及阴性组之间无明显差异。ER受体表达中容积ROI法最佳临界值为0.962×10^(-3)mm^(2)/s,曲线下面积(AUC)为0.724;PR受体表达中容积ROI最佳临界值为0.929×10^(-3)mm^(2)/s, AUC为0.803。三种测量方法的ADC值与HER-2受体的表达相关性不明显。结论三种ROI法测得ADC值能用于预测PR与ER情况,其中容积ROI法测得的ADC值在预测PR方面诊断效能最高。

Significance of the Expression of CyclinD1 and Ki67 Antigen in Nasopharyngeal Carcinoma

Objective: To detect the expression of cyclinD1 and Ki67 in nasopharyngeal carcinoma (NPC) and their correlation with the biological behaviors and prognosis. Methods: 56 cases of biopsy specimens of NPC which had been embedded with para?n in 1996 in our hospital were collected and immunostained with cyclinD1 and Ki67 monoclonal antibodies by means of the streptavidin peroxides method. The patients were followed up periodically, and then their biological behaviors and prognosis were statistically analyzed. Results: The percentage of cyclinD1 and Ki67 positive cells in the NPC specimens ranged from 0–54% and 0–31% respectively. The staining was nuclear. Of the 56 cases, 30 cases (56.6%) highly expressed cyclinD1 or Ki67 HPI and 26 cases (46.4%) lowly expressed cyclinD1, while only 16 cases (28.6%) showed Ki67 HPI (high proliferated index) and 40 cases (71.4%) showed Ki67 LPI (low proliferated index). Patients who lowly expressed cyclinD1 or highly expressed Ki67 had a higher radiosensitivity and a better prognosis. Conclusion: CyclinD1 and Ki67 immunohistochemical staining is considered to be useful, not only as an independent factor of radiosensitivity and prognosis respectively, but also as a means of determining the optimum treatment for each individual patient with NPC.

Measurement of Serum Total and Free Prostate-Specific Antigen for Breast Cancer Diagnosis in Women

Objective: To investigate the diagnostic value and the relationship between the clinicopathological features and the levels of total and free prostate-specific antigen (PSA) in women with breast cancer.Methods: Using the microparticle enzyme immunoassay system, we measured the concentrations of these markers in the sera of 85 women with breast cancer and in 30 healthy women.Rseults: The lowest detection level for both markers was 0.01 ng/ml. Free PSA levels were significantly higher in women with breast cancer than that in healthy women (P<0.05). The percentage of free PSA predominant subjects was 37.6% in breast cancer patients and 3.3% in healthy women. Cut-off values were 0.36 ng/ml for total PSA and 0.02 ng/ml for free PSA. In women with breast cancer, total PSA positivity was 23.5% and free PSA positivity was 27.1%. Compared to negatives, total PSA positive patients had a higher percentage of lymph node involvement tumours (P>0.05). However, patients with predominant free PSA had a higher percentage of early stage than patients with predominant PSA-ACT.Conclusion: Although the sensitivity of free PSA predominance is low (37.6%) in distinguishing women with breast cancer from healthy women, its specificity is high (97.0%).Free PSA predominance tends to be present in early stage tumours. These findings may indicate clinical significance of preoperative measurement of serum total and free PSA in women with breast cancer.

Challenges of incorporating gene expression data to predict HCC prognosis in the age of systems biology

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide.The recurrence of HCC after curative treatments is currently a major hurdle.Identification of subsets of patients with distinct prognosis provides an opportunity to tailor therapeutic approaches as well as to select the patients with specific sub-phenotypes for targeted therapy.Thus,the development of gene expression profiles to improve the prediction of HCC prognosis is important for HCC management.Although several gene signatures have been evaluated for the prediction of HCC prognosis,there is no consensus on the predictive power of these signatures.Using systematic approaches to evaluate these signatures and combine them with clinicopathologic information may provide more accurate prediction of HCC prognosis.Recently,Villanueva et al developed a composite prognostic model incorporating gene expression patterns in both tumor and adjacent tissues to predict HCC recurrence.In this commentary,we summarize the current progress in using gene signatures to predict HCC prognosis,and discuss the importance,existing issues and future research directions in this field.

Meta-analysis: prognostic value of survivin in patients with pancreatic cancer

Objective： The aim of the study was to conduct a systematic review of the literature evaluating survivin expres- sion in pancreatic carcinoma as a prognostic indicator. Methods： The relevant literatures were searched using PubMed, EMBASE, and Chinese Biomedicine Databases. A meta-analysis of the association between survivin expression and overall survival in patients with pancreatic cancer was performed. Studies were pooled and summary hazard ratios （HRs） were calculated. Subgroup analysis according to the location of survivin expression was also performed. Results： Seven eligible studies with a total of 448 patients were included in this study. Combined HR suggested that survivin expression had an unfavorable impact on survival of pancreatic cancer patients （HR = 1.65, 95% CI： 1.02-2.68）. When stratified according to the location of survivin expression, the combined HR showed that expression in the cytoplasm was significantly associated with poor prog- nosis of pancreatic cancer patients （HR = 2.09, 95% CI： 1.29-3.40）. In contrast, survivin expression in the nucleus was not significantly associated with poor prognosis （HR = 0.83, 95% CI： 0.24-2.81）, and the heterogeneity was highly significant （I2 = 87.2%, P = 0.005）. Conclusien： Survivin expression was associated with a poor prognosis in patients with pancreatic cancer. Cytoplasmic expression of survivin may be a prognostic factor for pancreatic cancer patients. Based on the current obtained data, there was no evidence that survivin expression in the nucleus had a significant impact on patients＇ overall survival.

子宫内膜癌患者血清CP2、CA125、唾液酸和癌胚抗原检测的临床意义

目的探讨肿瘤标志物CP2、CA125、唾液酸（SA）和癌胚抗原（CEA）检测对子宫内膜癌患者的临床意义。方法选取154例具有肿瘤标志物检测结果的子宫内膜癌患者的临床病理资料进行回顾性分析。结果子宫内膜癌患者血清CP2、SA、CA125和CEA水平升高的百分率分别为23．4％、36．8％、19．0％和30．3％。血清CP2水平升高与手术病理分期、病理分化程度、附件受累、腹腔细胞学检查阳性及盆腔淋巴结转移相关（P值分别为0．002、0．040、0．019、0．019、0．005）；血清SA水平升高与附件受累、腹腔细胞学检查阳性相关（P值分别为0．021、0．000）；血清CA125水平升高与病理分化程度、宫颈受累和盆腔淋巴结转移相关（P值分别为0．014、0．006、0．018）；CEA与各临床病理特征间均无相关性（P均〉0．05）。血清CP2、CA125和CEA水平升高与患者预后相关（P值分别为0．016、0．000、0．016），其中CA125水平与预后关系最为密切。结论子宫内膜癌缺乏特异性肿瘤标志物，CP2与子宫内膜癌临床病理特征相关性较强，CP2、CA125和CEA对患者预后有提示作用。