血清外泌体miRNAs在晚期胃癌患者化疗疗效预测中的价值

  目的  通过筛选晚期胃癌患者血清外泌体miRNAs,探讨外泌体miRNAs在化疗疗效预测中的价值。  方法  收集苏州大学附属第一医院2018年4月至2020年11月确诊为初治Ⅳ期胃腺癌患者36例病例资料,均接受不少于2个周期的Xelox或SOX方案化疗,根据实体肿瘤疗效评价标准（RECIST标准）分为敏感组和耐药组,收集患者首次化疗前的血清标本,提取血清外泌体RNA,行miRNAs测序,筛选出差异表达显著的miRNAs,并采用实时荧光定量PCR对筛选的miRNAs进行验证,使用受试者工作特征曲线（receiver operating characteristic curve,ROC）,判断验证后的外泌体miRNAs在疗效预测中的价值。  结果  36例Ⅳ期胃癌患者按照RECIST标准,分为敏感组15例,耐药组21例。两组患者血清外泌体中共筛选出527个差异表达的miRNAs,经qRT-PCR验证后,仅3个外泌体miRNAs差异具有统计学意义,ROC曲线预测miRNA-106a-5p、miRNA-1323、miRNA-202-3p与胃癌化疗疗效的曲线下面积分别为0.952、0.949、0.946,灵敏度分别为90.5%、90.1%、85.7%,特异度分别为:93.3%、86.7%、93.1%。  结论  检测晚期胃癌患者血清外泌体miRNA-106a-5p、miRNA-1323、miRNA-202-3p,可能对化疗疗效具有一定的预测价值。      

外泌体miRNAs在乳腺癌肿瘤微环境中的研究进展

乳腺癌是全球女性最常发生的恶性肿瘤,患者死亡的主要原因是复发、转移和耐药性的出现.研究已经证明,外泌体介导癌细胞与肿瘤微环境之间的信息交流,外泌体携带的miRNAs通过差异表达于乳腺癌细胞,在微环境中影响癌基因表达的调控,介导乳腺癌细胞的信号通路,调节癌细胞周期进程以及重塑肿瘤相关成纤维细胞等,从而促进乳腺癌的发生、发...     

外泌体在胃癌诊疗中的研究进展

胃癌的发病率和死亡率均较高,早诊早治极为关键,需要更加灵敏的诊断技术与精准的治疗手段,才能在胃癌早期及时发现并将其有效遏制。外泌体是细胞分泌的一种囊泡,其携带多种具有生物活性的小分子,如蛋白质、RNA、DNA等。外泌体可作为细胞间通讯的一种功能介质,传递多种生物信息并介导受体细胞的生物进程。在肿瘤中,外泌体不仅积极参与肿瘤微环境的信息传递,而且具有调节细胞免疫应答的能力。近年来外泌体在肿瘤领域的相关研究取得了一系列进展,其参与胃癌增殖、侵袭、复发和转移、耐药以及新生血管形成等方面的调控。外泌体在胃癌的早期诊断与精准治疗方面具有重要意义,值得深入探索。本文就外泌体在胃癌诊疗中的研究进展进行综述。     

血清和尿液中外泌体miRNAs的表达水平对肾细胞癌的诊断价值

目的:研究血清和尿液中外泌体miRNAs的表达水平对肾细胞癌(RCC)的诊断价值。方法:选择本院2018年11月至2020年08月诊治的68例RCC患者（RCC组）进行前瞻性分析,并将RCC患者根据临床分期进行分组,以本院同期收治的60例肾脏良性病变患者作为对照组。检测患者血清和尿液中外泌体miRNAs相对表达量,分析血清和尿液中外泌体miRNAs在肾细胞癌中的诊断价值。结果:RCC组患者血清、尿液中miR-210、miR-21、miR-153、miR-1233和miR-221表达量均明显高于对照组,miR-34a表达量均明显低于对照组（P＜0.05）;血清中ROC曲线显示AUC最大的为miR-221,其诊断敏感度为79.40%,特异度为95.00%;尿液中最大的为miR-34a,其敏感度为85.30%,特异度为88.30%;不同临床分期RCC患者的血清miR-210、miR-153表达量以及尿液miR-153表达量无显著差异（P＞0.05）,但血清和尿液中的miR-21、miR-34a、miR-1233、miR-221表达量以及尿液miR-210表达量在不同分期RCC患者中存在显著差异（P＜0.05）;血清中,miR-210、miR-153与临床分期无相关性（P＞0.05）,miR-21、miR-1233、miR-221与临床分期呈正相关,miR-34a与临床分期呈负相关（P＜0.05）;尿液中,miR-210、miR-153与临床分期无相关性（P＞0.05）,miR-21、miR-1233、miR-221与临床分期呈正相关,miR-34a与临床分期呈负相关（P＜0.05）。结论:RCC患者血清、尿液外泌体miR-210、miR-21、miR-34a、miR-153、miR-1233和miR-221表达量较良性肾脏病变患者存在显著差异,同时miR-21、miR-34a、miR-1233、miR-221表达量均与RCC患者病理分期存在显著相关性,可为疾病进展评估提供参考。     

胃癌患者血清外泌体粒径的临床意义

目的 探讨胃癌患者血清外泌体粒径的变化及其在胃癌患者预后评估方面的临床意义。方法 收集2021年5月至2022年2月皖南医学院收治的胃癌病例,同时收集同期健康体检者作为对照组。采用PEG沉淀法提取32例胃癌患者及26例健康志愿者的血清外泌体,运用纳米颗粒跟踪技术(NTA)检测胃癌血清外泌体的粒径和浓度;分析血清外泌体粒径大小与胃癌临床病理特征的关系;采用受试者工作特征曲线(ROC)分析血清外泌体粒径和浓度检测对胃癌分期的预测价值。结果 胃癌患者血清外泌体的浓度为(9.53±6.24)×10⁷particals/ml,高于健康对照组的(6.14±3.43)×10⁷particals/ml,差异有统计学意义(P<0.05);且胃癌患者血清外泌体粒径为(108.35±16.63)nm,显著小于健康对照组的(128.23±20.24)nm,差异有统计学意义(P<0.001)。血清外泌体粒径与胃癌患者的分期相关,即随着胃癌分期的增加,血清外泌体的粒径显著下降(P<0.05);ROC曲线结果显示,血清外泌体粒径诊断胃癌的灵敏度、特异度分...     

外泌体蛋白质在消化系统恶性肿瘤中的诊断价值

消化系统恶性肿瘤是人类常见的恶性肿瘤之一,其高发病率和晚期的低生存率给患者、家庭和社会带来沉重的疾病负担。然而,现有肿瘤筛查手段大多具有侵入性或操作复杂等特征,不利于开展大规模的人群筛查和长期随访,所以基于循环肿瘤DNA(circulating tumor DNA,ctDNA)、循环肿瘤细胞（circulating tumor cell,CTC）和外泌体（exosome）等新型生物标志物的液体活检技术具有广阔的发展前景。外泌体是由活细胞分泌、具有脂质双层膜的细胞外囊泡,相比于其他标志物其具有稳定性高、分布广泛、数量多等优势。外泌体携带的各种蛋白质能够反映来源细胞的特征,对于肿瘤早期诊断具有重要的研究价值。本文对近5年外泌体蛋白质作为消化系统恶性肿瘤早期诊断生物标志物的研究成果进行综述,并总结上述研究的主要特征和局限性,为促进外泌体蛋白质的临床转化提供参考依据。     

外泌体源性细胞外microRNAs 在泌尿系统恶性肿瘤中的研究进展*

microRNAs（miRNAs）是一种内源性单链非编码微小RNAs分子,可通过碱基互补方式与靶mRNA 的3’非翻译区（3’UTR ）特异性结合诱导其降解或抑制其翻译,从而在转录后水平有效地沉默靶基因的蛋白表达。miRNAs因可以上述方式调节癌基因或抑癌基因表达,故其广泛参与了肿瘤的发生发展过程。本文概括了miRNAs的起源、功能及生物体液中外泌体（exosome）源性细胞外miRNAs的稳定性。同时对从尿液外泌体中寻找泌尿系统恶性肿瘤潜在miRNA 标记物的现实可行性以及尿液中外泌体源性miRNAs在前列腺癌、膀胱癌及肾癌中作为生物标记物的潜能进行综述。     

血清外泌体miR-148a联合miR-106a检测用于胃癌筛查的研究探讨

目的:寻找合适的外泌体mi RNA作为肿瘤生物标志物,辅助临床进行胃癌筛查。方法:将mi R-148a及mi R-106a作为潜在标志物,研究两种mi RNA在癌组织及癌旁组织表达的差异性。选取2017年9月至2018年9月在福建省立医院诊治的初诊胃癌术后标本共37对(胃癌组织及癌旁组织)进行组织学mi RNA检测。选取初诊胃癌患者83例为胃癌组,良性病变的患者78例为对照组,全部进行血清外泌体mi RNA检测。结果:与癌旁组织相比,癌组织中mi R-148a表达水平降低,mi R-106a表达水平升高,联合检测2^-△△CP[△CP=CP₍(mi R-148a))-CP₍(mi R-106a))]值降低。与对照组相比,胃癌患者中血清外泌体mi R-106a表达水平降低,联合检测2^-△△CP值升高。血清外泌体联合检测2-△△CP值对胃癌组和对照组鉴别的曲线下面积[AUC为0.844(95%CI:0.782～0.905,P<0.001)],大于mi R-148a及mi R-106a单独检测,其cu...     

外泌体对胃癌转移的作用及其在诊断中的应用研究进展

摘要胃癌是对各种治疗策略均具有一定抵抗性的恶性肿瘤之一, 其发病率及死亡率在近些年居高不下。目前胃癌的治疗方法以手术切除为主, 尽管术后辅以放化疗、免疫治疗及中医治疗等手段, 但其预后及5年生存率仍较低。目前尚缺乏高效的早期诊断胃癌的方法, 使得多数患者在晚期症状严重时才得以发现。外泌体内包含DNA、RNA、蛋白质、脂质等多种生物大分子物质, 其参与肿瘤发展的过程, 并且影响肿瘤的增殖及转移, 尤其是其中丰富的生物大分子物质可以反映肿瘤的进展程度, 这也给早期胃癌的诊断提供了新的思路, 可以将其作为非侵入性的诊断标志物。本文就外泌体在胃癌转移及早期诊断中的应用进行综述。      

外泌体miRNA在胃癌发病机制中的研究进展

胃癌是消化系统常见恶性肿瘤之一,其发病率、死亡率均较高,患者预后差,疾病负担重。外泌体是细胞分泌的具有磷脂双分子层结构的囊泡物质,直径20～200 nm,内含蛋白质、核酸、脂质等生物活性物质,在细胞信号传导和信息传递中发挥重要作用。胃癌的发病机制与外泌体miRNA的调控密切相关,其通过调控丝裂原活化蛋白激酶1(mitogen-activated protein kinase 1,MAPK1)、细胞分裂蛋白激酶6(cyclin-dependent kinase 6,CDK6)及血管内皮细胞生长因子（vascular endothelial growth factors,VEGF）的表达等机制来调控细胞增殖、凋亡,从而影响胃癌的发生及进展。全文就外泌体miRNA在胃癌发病机制中的研究进展作一综述。     

Evaluation of CA72-4 as a tumor marker in patients with gastric cancer

The clinical efficacy of CA72-4 for gastric cancer was studied in comparison with CEA and CA19-9. These 3 markers were examined simultaneously, preoperatively in 156 cases of gastric cancer. The positive rate of CA72-4 was higher than of CA19-9 and was equivalent to CEA. There was no significant difference between differentiated and undifferentiated carcinoma in these 3 markers. However, the positive rates of CEA and CA72-4 were significant higher in the cases with lymph node metastasis and curative grade B, C. The combination assay of CEA and CA72-4 was valuable because the tumor markers were considered to be independent of each other. Cases positive for both CEA and CA72-4 simultaneous were significantly more frequent among the cases with lymph node metastasis and in the serosa-invasive cases. In conclusion, CA72-4 is more important than CA19-9 as a tumor marker in gastric cancer patients.     

CA125联合 CA19－9、CEA、CA72－4检测在上皮性卵巢癌诊断中的意义

目的：阐明联合检测糖类抗原（CA125、CA19－9、CA72－4）与癌胚抗原（CEA）在上皮性卵巢癌中的诊断意义。方法：对81例上皮性卵巢癌患者,81例良性卵巢肿瘤患者以及作为对照的80例健康体检者血清中的 CA125、CA19－9、CA72－4与 CEA 进行检测。采用 ROC 曲线及 AUC、Logistic 回归分析评估上述血清标记物对上皮性卵巢癌的诊断意义。结果：卵巢癌患者血清肿瘤标记物 CA125、CA19－9、CA72－4的水平与阳性率明显高于良性卵巢肿瘤以及对照组健康体检者（P ＜0．05）。ROC 曲线显示 CA125、CA19－9、CEA 与CA72－4曲线下面积分别为0．904±0．025、0．670±0．042、0．497±0．046 and 0．821±0．033。联合检测上述肿瘤标记物显示最高的敏感性（91．4％）与较好的特异性（83．9％）。与其他单一肿瘤标记物相比,CA125显示最高的敏感性与较好的特异性。结论：联合检测 CA125、CA19－9、CEA 与 CA72－4可以提高上皮性卵巢癌早期诊断的敏感性与准确性。     

Clinical significance of CA125 and CA72-4 in gastric cancer with peritoneal dissemination

Background  

Serum tumor markers have been shown to correlate with the clinical status of patients with advanced gastric cancer. However, the clinical significance of each tumor marker in patients with peritoneal dissemination has not been fully verified.     

Serum exosomal microRNAs as novel biomarkers for multiple myeloma

Accumulating studies have focused on circulating microRNAs, which might be potential biomarkers for different malignancies. The aim of this study was to investigate the potential of serum exosomal microRNAs to be novel serum biomarkers for smouldering myeloma (SMM) or even multiple myeloma (MM). The levels of serum exosomal microRNAs and serum circulating microRNAs were measured in healthy individuals and patients with SMM (n = 20) or MM (n = 20). Serum exosomal microRNAs and serum circulating microRNAs were extracted from serum, and the expression levels of selected microRNAs were quantified by real‐time polymerase chain reaction (PCR). The levels of serum exosome‐derived miR‐20a‐5p, miR‐103a‐3p, and miR‐4505 were significantly different among patients with MM, patients with SMM, and healthy individuals, while there were differences in the levels of let‐7c‐5p, miR‐185‐5p, and miR‐4741 in patients with MM relative to those in SMM patients or healthy controls. Additionally, a significant correlation was rarely found between the levels of serum and exosomal microRNAs. This study shows that serum exosomal microRNAs can be used independently as novel serum biomarkers for MM.     

Preoperative hCGbeta and CA 72-4 are prognostic factors in gastric cancer

In gastric cancer, the role of tumour markers in assessment of prognosis is unconfirmed. In our study, we evaluated the prognostic significance of serum tumour markers carcinoembryonic antigen (CEA), CA 19-9, CA 72-4, CA 242 and free beta subunit of human chorionic gonadotropin (hCGbeta) in gastric cancer. Preoperative serum samples were obtained from 146 patients with gastric cancer, including 29 with stage I, 11 with stage II, 42 with stage III and 64 patients with stage IV cancer. Quantitation of CEA, CA 19-9, CA 72-4 and CA 242 in serum was performed with commercial assays. HCGbeta was measured with an in-house immunofluorometric assay based on monoclonal antibodies specific for the free beta-subunit of hCG. Survival analysis was performed with Kaplan-Meier life-tables and log-rank test, and with multivariate Cox regression analysis. Disease-specific cumulative 2-year survival rate was 40%. Serum levels of CEA, CA 72-4, CA 242 and hCGbeta showed significant correlation with stage (p<0.027); for CA 19-9 the association was of borderline significance (p=0.056). Of the studied markers, CA 19-9, CA 72-4, CA 242 and hCGbeta were found to be prognostic factors in univariate analysis (p< 0.022). In multivariate analysis, stage had the statistically most significant association with prognosis followed by hCGbeta, tumour histology according to the Laurén classification and by CA 72-4. In gastric cancer, tumour markers hCGbeta and CA 72-4 are independent prognostic factors in addition to stage and histological type of the tumour.     

Significance of CA72-4 as a follow up of recurrent gastric cancer--comparison with CEA and CA19-9]

We studied a significance of serum CA72-4 as a follow up of recurrent gastric cancer in 24 recurrent cases with gastric cancer performed combination assay of CEA, CA19-9 and CA72-4. Positive rate of CA72-4 was 58.3%, which was almost same as that of CEA. Lymph node metastasis and peritoneal dissemination were observed relatively high rate in positive cases with serum CA72-4. Comparison of an elevation time of CEA and CA72-4 in recurrent cases showed that CEA earlier than CA72-4 was 3 cases, CA72-4 earlier than CEA was 3 cases, and the others were about same. These results indicated that CA72-4 was a useful tumor marker as a follow up of recurrent gastric cancer.     

血清CEA、CA72-4及CA125联合诊断胃癌术后腹膜转移

目的:探讨血清CEA、CA72-4及CA125联合诊断胃癌术后腹膜转移的价值,为临床诊治提供参考。方法:以我院于2015年11月至2016年11月因胃癌术后在本院复查且相关临床资料齐全患者120例作为研究对象并进行回顾性分析,按照有无腹膜转移分为转移组（38例）和无转移组（82例）。对比两组患者的血清CEA、CA72-4及CA125变化及单项诊断效能,并采用ROC曲线法对比三种肿瘤标志物的诊断效能。结果:转移组患者的血清CEA、CA72-4及CA125水平均高于无转移组,差异有统计学意义（P＜0.05）。三个单项指标比较,CA125灵敏度为73.3%,特异度为81.8%,均为三者最高,差异均有统计学意义（P＜0.05）。联合诊断比较,CEA+CA72-4+CA125联合检测的灵敏度最高（91.7%）,但特异度最低（41.7%）,差异均有统计学意义(P＜0.05)。结论:胃癌术后腹膜转移患者血清CEA、CA72-4及CA125均升高,且单项诊断CA125的灵敏度及特异度最高,而三项联合诊断的灵敏度最高,但特异度最低,值得临床参考。     

卵巢癌血清HE4、CA72-4、CA125水平测定

目的 探讨卵巢癌血清人附睾分泌蛋白4（HE4）、CA72-4、CA125水平及临床意义.方法 入组我院收治的卵巢癌患者45例、卵巢良性病变30例,并纳入同期女性健康体检者30例作为对照,采用电化学发光法分别检测各组血清中HE4、CA72-4、CA125水平.结果 卵巢癌组血清HE4、CA72-4、CA125水平均高于卵巢良性病变组和健康对照组（P〈0.05）.HE4以〉150 pmol·L-1,CA72-4以5.3 u·mL-1,CA125以35 u·mL-1为阳性参考值,三者联合检测的敏感性为93.3%,特异性为73.3%.结论 卵巢癌患者血清中HE4、CA72-4、CA125处于高水平,联合检测可提高卵巢癌的诊断率.     

miRNAs as biomarkers in prostate cancer

Current prostate cancer (PCa) diagnosis is based in the serum prostate-specific antigen biomarker and digital rectal examination. However, these methods are limited by a low predictive value (24?C37?%) and a high risk of mistaken results. During last years, new promising biomarkers such as Prostate Cancer Antigen 3 (PCA-3) and TMPRSS2-ETS fusion genes have been evaluated for their clinical use. However, the search of new biomarkers that could be used for PCa diagnosis and prognosis is still needed. Recent studies have demonstrated that the aberrant expression of microRNAs (miRNAs), small non-coding RNAs that negatively regulate gene expression, is related with the development of several cancers, including PCa. Since miRNAs serve as phenotypic signatures of different cancers, they appear as potential diagnostic, prognostic and therapeutic tools. Here, we review the current knowledge of miRNA expression patterns in PCa and their role in PCa prognosis and therapeutics.     

血清 CA72-4、CA19-9在消化系统癌的表达

[目的]评价血清肿瘤标志物CA72-4、CA19-9在消化系统癌中的临床意义.[方法]采用免疫放射量度分析法测定129例消化系统癌及35例消化系统良性病变患者血清CA72-4、CA19-9水平.[结果]CA72-4、CA19-9在129例消化系统癌的阳性表达率分别为56.59%和43.41%,共有34例二者表达阳性,其阳性率26.36%.而消化系统良性病变阳性表达率均为5.71%,而且无一例交叉阳性,差异有显著性.CA72-4,CA19-9水平与消化系统癌有无转移有关,而且行根治术后CA72-4、CA19-9明显下降,而非根治手术者则手术前后差异无显著性.[结论]血清CA72-4、CA19-9对鉴别消化系统上皮肿瘤的良恶性有较好的鉴别诊断价值,联合检测比单项检测检测率高,而且对于预测消化系统癌有无转移及判断手术疗效也有一定参考价值.