乳腺癌竞争内源性RNA网络构建与分析

目的:通过对癌症基因组图谱(The Cancer Genome Atlas，TCGA)数据库中的乳腺癌数据进行综合分析，寻找在乳腺癌中差异表达的长链非编码RNA(long non-coding RNA，lncRNA）、微小RNA（microRNA，miRNA）和信使RNA（messenger RNA，mRNA），构建乳腺癌竞争内源性RNA（competing endogenous RNA，ceRNA）网络，识别和预测ceRNA网络在乳腺癌中的作用。方法:下载TCGA数据库中乳腺癌组织样本基因表达谱数据，寻找差异表达的lncRNA、miRNA和mRNA，通过miRcode、miRTarBase、TargetScan和miRDB四个数据库对差异表达的RNA之间的关系进行分析，构建以上调和下调的miRNA为中心的ceRNA网络。采用Kaplan-Meier法分析乳腺癌ceRNA网络中的lncRNA、miRNA和mRNA表达量与患者生存预后的关系，采用基因富集分析法对乳腺癌ceRNA网络中mRNA基因功能和调控通路进行分析。结果:在乳腺癌中异常表达的350个lncRNA、185个miRNA和2 928个mRNA中，分别有23个lncRNA、27个miRNA、70个mRNA参与构建乳腺癌的ceRNA网络。Kaplan-Meier生存分析显示，lncRNA MAGI2-AS3（P=0.01）、GRIK1-AS1（P=0.03）以及miRNA hsa-miR-301b（P=0.01）、hsa-miR-503（P=0.04）和mRNA CCNE1（P=0.01）、KPNA2（P=0.02）、FLI1（P=0.02）、TGFBR2（P=0.02）这8个基因与乳腺癌患者的生存预后显著相关。70个mRNA主要被富集到20条通路上，其中有15条通路与肿瘤有关，最显著的通路为“Pathways in cancer”。结论:ceRNA网络在乳腺癌中发挥着重要的作用，多种差异表达基因与乳腺癌预后相关，可能成为潜在的肿瘤诊断标志物和治疗靶点。     

基于生物信息学技术对结直肠癌相关lncRNA、miRNA和mRNA的筛选及其部分生物学功能的分析

[摘要] 目的：筛选TCGA数据库中结直肠癌（CRC）差异表达的lncRNA、miRNA和mRNA,探讨其与CRC预后的关系及相关生物学功能。方法：从TCGA数据库中下载CRC样本的RNA测序（RNA-Seq）数据及miRNA-Seq 数据并进行分析,利用R程序筛选出差异表达的lncRNA、miRNA和mRNA。通过miRcode、TargetScan 和miRTarbase 3 个数据库对差异表达的RNA之间的关系进行分析整合,构建CRC中的lncRNA-miRNA-mRNA ceRNA网络。用Kaplan-Meier 法分析ceRNA网络中的lncRNA、miRNA和mRNA表达量与患者生存预后的关系,后用GSEA功能富集分析软件分析出参与CRC发生发展的信号通路。结果：共鉴定出CRC中614 个差异表达的lncRNA、244 个差异表达的miRNA、12 672 个差异表达的mRNA;构建了由139 个lncRNA、37 个miRNA和228 个mRNA组成的ceRNA 网络;发现有58 个lncRNA、23 个miRNA、150 个mRNA与CRC的预后相关。GSEA富集分析结果显示,mRNA主要参与Notch、Hedgehog 和TGF-β 等信号通路。结论：成功构建CRC 相关ceRNA 网络,并筛选出与CRC预后相关的lncRNA、miRNA和mRNA,为后续深入开展CRC的临床研究及基础实验研究提供有价值的前期基础。     

基于竞争内源性RNA网络探讨槲皮素在肺腺癌中的作用靶点

目的:利用从肺腺癌（LUAD）数据集中筛选的差异表达基因（DEGs）、差异表达lncRNA（DElncRNA）及其上游miRNA,构建LUAD的竞争内源性RNA网络（ceRNA）,探索槲皮素可能的作用靶点。方法:从基因表达综合数据库（GEO）及肿瘤基因组图谱数据库（TCGA）中检索并筛选LUAD基因及lncRNA表达数据集,对差异表达基因（DEGs）进行富集和功能注释。使用在线数据库预测miRNA及lncRNA,建立ceRNA调控网络,并通过网络药理学分析槲皮素的药物靶点。结果:构建了AURKA与上游hsa-miR-363-3p及AP000553.1、LINC00858、AL354707.1的ceRNA调控网络,槲皮素与5DOS对接良好。结论:AP000553.1、LINC00858、AL354707.1与hsa-miR-363-3p竞争性调控AURKA,进一步影响LUAD预后,槲皮素可作用于AURKA。     

肺腺癌竞争内源性RNA网络的综合分析:基于肿瘤基因组图谱数据库

目的:基于肿瘤基因组图谱数据库（TCGA）架构肺腺癌（LUAD）竞争内源性RNA（ceRNA）网络，鉴定潜在的生存关联性生物标志物，并确定特异性治疗的小分子药物。方法:依据纳入研究标准，利用Edger软件筛选LUAD组织与正常组织(mRNA、lncRNA和miRNA)差异表达的基因。通过miRcode、miRDB、TargetScan和miRanda数据库对差异表达的RNA之间的关系进行分析，构建ceRNA网络。采用Kaplan-Meier方法分析ceRNA网络中的RNA表达量与生存预后的关系，通过富集分析对网络中的mRNA基因功能和调控通路进行分析。通过Cmap数据库筛选治疗LUAD的特异性小分子药物。利用D-lnc软件确定与关键的lncRNA相关的特异性小分子药物。结果:mRNAs(ELAVL2和PBK)、miRNAs(miR-13和miR-210)和lncRNAs(AP002478.1、DSCAM-AS1、LINC00269、LINC00470和LINC00483)与总生存期(OS)关系密切。喜树碱和甲萘醌有可能逆转LUAD的状态。卡铂、多西紫杉醇、帕比司他被确定为与关键lncRNA密切相关的药物。结论:ceRNA网络在LUAD中发挥重要作用，多种差异表达RNA与LUAD预后相关，可能成为潜在的肿瘤诊断标志物和治疗靶点。     

基于lncRNA-miRNA-mRNA调节网络胃癌关键基因筛选与分析

目的胃癌的分子发病机制与预后仍是亟待解决的难题。本研究通过癌症基因组图谱(the cancer genome atlas,TCGA)数据库筛选出在胃癌中表达失调的基因,构建长链非编码RNA(long non-coding RNA,lncRNA)-微小RNA(microRNA,miRNA)-信使RNA(mRNA)调节网络,寻找并分析网络中与胃癌患者预后相关的关键调控基因,为胃癌提供新型分子标志物。方法从TCGA官方网站中下载胃癌RNA测序数据和临床数据,使用R软件edgeR包分析胃癌中差异表达的lncRNA、miRNA和mRNA,构建差异lncRNA-miRNA-mRNA调控网络。使用R软件中的survival包对调控网络中的基因进行分析,寻找与胃癌预后相关的关键基因。使用Kaplan Meier-plotter在线数据库分析这些关键基因的预后作用。结果共有62个lncRNA、10个miRNA和10个mRNA分子参与调控网络的构建。Kaplan-Meier生存分析显示,2个mRNA(ATAD2、SERPINE1),10个lncRNA(AC018781.1、ADAMTS9-AS1、ADAMTS9-AS2、AL139002.1、AL391152.1、C15orf54、IGF2-AS、LINC00326、NKX2-1-AS1、POU6F2-AS2)和2个miRNA(miR-145、miR-508)与胃癌患者预后有统计学意义的关联,P<0.05。Kaplan Meier-plotter数据库分析显示,mRNA ATAD2(HR=1.66,95%CI为1.32~2.08,P<0.001)和SERPINE1(HR=1.36,95%CI为1.13~1.64,P=0.001)与胃癌患者的总体生存率差异有统计学意义的关联。结论成功构建了胃癌lncRNA-miRNA-mRNA调节网络后,识别出了调控网络中预后相关基因,这些基因可能作为胃癌新型的分子标志物。     

基于GEO数据库的小细胞肺癌lncRNA-miRNA-mRNA网络的构建与潜在的诊治靶点分析

目的 筛选参与小细胞肺癌(SCLC)发生发展的ncRNAs,预测其诊治的潜在靶点。方法 对人类肿瘤相关基因表达汇编(Gene Expression Omnibus, GEO)数据库中获得的表达谱芯片数据进行差异基因分析，构建了ceRNA网络，并进行功能富集分析、PPI网络构建。收集7例手术治疗的小细胞肺癌患者，采用实时定量PCR(qPCR)对部分差异基因(lncRNA、mRNA和miRNA)进行临床样本验证。结果 共有99个lncRNA、46个miRNA和73个mRNA分子参与调控网络的构建。GO和KEGG分析表明失调的mRNA主要参与小细胞肺癌的细胞癌变、增殖以及转移。PPI网络分析提示46个基因被认为是中心基因。qPCR结果显示，与癌旁组织比较，小细胞肺癌组织中lnc-ENST00000430027.3呈相对高表达(P<0.001),hsa-miR-143-5p呈相对低表达(P<0.01),FANCA呈相对高表达(P<0.01)。结论 构建“lncRNA-miRNA-mRNA”的ceRNA调控网络，可为小细胞肺癌诊治提供新的依据和靶点，为小细胞肺癌诊断和治疗的分子...     

长链非编码RNA与mRNA在胰腺癌中的差异表达及其预后价值

目的：对基因芯片表达汇编（GEO）数据库和癌症基因组图谱（TCGA）数据库中的胰腺癌数据进行生物信息学分析,探讨长链非编码RNA （lncRNA）与mRNA在胰腺癌中的差异表达和预后价值。方法：首先对GEO数据库中的胰腺癌数据注释获得mRNA和lncRNA,并对芯片中的mRNA和lncRNA取交集获得差异mRNA和lncRNA。然后对差异mRNA和lncRNA进行基因分析,同时对TCGA数据库中胰腺癌的相关数据进行生存分析。结果：通过基因分析获得与胰腺癌相关可信度高的差异mRNA 1 147个,lncRNA 336个,通过基因本体（GO）和京都基因与基因组百科全书（KEGG）分析,构建lncRNA-mRNA共表达网络、lncRNA-mRNA-pathway网络、信号通路关系网络及蛋白质相互作用网络,结果证明mRNA和lncRNA对胰腺癌的发生发展有着重要影响;生存分析发现有12个lncRNA与胰腺癌的预后相关,分别是ATP1A1-AS1、CBR3-AS1、CTD-3080P12.3、FAM66D、FAM87A、FLJ38576、LINC00476、LINC00574、LINC01554、PYY2、LINC00857、OVOL1-AS1。结论：lncRNA对胰腺癌的发生发展及预后有显著影响,有望为胰腺癌的靶向治疗和预后评估提供新的治疗靶点和分子标志物。     

基于癌症基因组图谱数据分析筛选结肠癌预后相关长链非编码RNA

目的:通过分析癌症基因组图谱（TCGA）数据库中有关结肠癌的转录组测序数据，筛选结肠癌预后相关长链非编码RNA（lncRNA），寻找新的lncRNA结肠癌分子标志物。方法:下载TCGA数据库中结肠癌转录组测序数据及结肠癌患者临床资料，利用R语言进行数据整理。采用edgeR包筛选差异表达lncRNA，采用单因素Cox回归模型对差异表达lncRNA进行生存分析。提取与这些lncRNA共表达的编码基因，行京都基因与基因组百科全书（KEGG）分析。结果:差异表达分析共筛选出227个在肿瘤各TNM分期中均异常表达的lncRNA，其中表达上调169个，表达下调58个。生存分析鉴定出15个差异表达lncRNA与预后显著相关（P<0.05），其中2个为保护因素，13个为危险因素。KEGG分析发现，这些预后相关lncRNA 的共表达基因主要富集在核糖体生物合成、mRNA监视通路等。结论:通过挖掘TCGA结肠癌数据集，发现了一些具有预后意义的异常表达lncRNA，为后续深入研究其功能奠定了基础，这些lncRNA有望成为新的结肠癌诊断或治疗分子标志物。     

ceRNA在肿瘤中的研究进展

竞争性内源RNA(competing endogenous RNA,ceRNA)是一类能与miRNA结合位点（miRNA response element,MRE）结合从而抑制miRISC形成,并能进一步增加相应mRNA的表达来达到RNA间相互沟通及转录后调控基因表达的一类非编码RNA。ceRNA主要包括长链非编码RNA（long non-coding RNA,lncRNA）、环状RNA（circular RNA,circRNA）、假基因、人工合成miRNA抑制剂及病毒miRNA抑制剂等。目前越来越多的研究表明ceRNA在肿瘤的基因调控及肿瘤细胞增殖、凋亡、细胞周期、侵袭和转移等各种生物过程中发挥重要作用。本文从ceRNA分类、调控网络及ceRNA在不同肿瘤中的研究进展作一综述。     

m6A结合蛋白IGF2BP1在肝细胞癌中的基因调控网络分析

目的 分析m6A阅读器胰岛素样生长因子2-mRNA结合蛋白1（insulin-like growth factor 2 mRNA-binding protein 1，IGF2BP1）在肝细胞癌（hepatocellular carcinoma，HCC）中的表达水平及其对HCC患者预后的影响，并探讨IGF2BP1在HCC发生发展中的作用及其潜在机制。方法 基于5对HCC癌及相应癌旁组织mRNA-seq数据和TCGA数据库LIHC的mRNA-seq数据综合分析IGF2BP1在HCC中的表达情况，同时利用TCGA数据库中343例HCC患者的临床随访资料分析IGF2BP1表达水平对HCC患者总生存期的影响。基于TCGA数据库筛选IGF2BP1的共表达mRNA，并利用m6Avar在线网站预测mRNA的m6A位点及其RNA结合蛋白等信息，最终构建IGF2BP1的基因调控网络。结果 IGF2BP1基因在HCC中表达上调（log2FC HCC转录组数据=10.684，P<0.001；log2FC TCGA-LIHC数据集=7.032，P<0.001）。生存分析显示IGF2BP1低表达的HCC患者中位生存时间为5.84年，IGF2BP1高表达患者为4.44年，高表达患者总生存期缩短（P=0.011）。22个差异表达的mRNA与IGF2BP1存在靶向结合关系，并与其表达水平呈正相关。其中，HMGA2等15个高表达mRNA的HCC患者总生存期缩短。HMGA2、PEG10、CEP55、RHO、CDC6和KIF23基因中的潜在m6A甲基化位点位于mRNA 3'UTR端的miRNA结合区域。结论 IGF2BP1在HCC中高表达且导致患者总生存期缩短。IGF2BP1可能通过m6A甲基化及miRNA抑制作用的方式上调mRNA的表达，促进HCC发生并导致不良预后。     

洛铂联合多西他赛行肿瘤细胞减灭术加腹腔热灌注化疗治疗腹膜癌的临床观察

目的 分析洛铂联合多西他赛行肿瘤细胞减灭术（cytoreductive surgery, CRS）加腹腔热灌注化疗（hyperthermic intraperitoneal chemotherapy, HIPEC）治疗腹膜癌（peritoneal carcinoma, PC）的围手术期安全性及疗效。 方法 PC患者行CRS+HIPEC治疗,药物为洛铂50 mg/m2、多西他赛60 mg/m²,加入12 000 ml 0.9%氯化钠溶液加热至（43±0.5）℃持续灌注60 min。记录术后6天体温和心率变化、围手术期不良事件、血常规及血生化指标、术后患者恢复情况及生存结果。结果 90例PC患者行95次CRS+HIPEC,手术时间180~450 min (中位数485 min）;术后6天最高体温、心率分别为36.4℃~38.6℃（中位数37.5℃）、76~124 bpm（中位数100 bpm）,严重不良事件16例,包括围手术期死亡2例。中位生存期20.8月（95%CI: 13.1~25.8月）,1、3、5年生存率分别为75.6%、45.6%、43.3%。 结论 洛铂联合多西他赛进行CRS+HIPEC治疗PC安全性可接受,有助于延长患者生存期。     

Endoscopic Endonasal Dacryocystorhinostomy: Best Surgical Management for DCR

EEDCR is a highly rewarding Endoscopic procedure for management of dacryocystitis when epiphora does not respond to medications or repeated syringing of nasolacrimal duct. It is a simple, less time consuming, safe but skilful, highly satisfying surgery both for the patients as well as the surgeons. There is very big advantage of EEDCR, it is close 100% successful procedure, even if there is recurrence of epiphora it is again correctable fully with no residual affects. EEDCR is far more superior to External DCR/Laser DCR and there are definite reasons for it. A total number of 578 cases have been operated by me from April 1, 2005 to March 31, 2011, only very few reoccurrences were there and they were corrected easily so much so that it can be said that it is a close 100% successful procedure and best surgical management of DACRYOCYSTITIS up to date. The successful outcome was defined as symptomatic relief from epiphora and dacryocystitis and a patent nasolacrimal duct upon syringing at the end of procedure and on follow up of patient.     

Denosumab in patients with cancer and skeletal metastases: A systematic review and meta-analysis

Background

We conducted a systematic review of the literature to determine the efficacy and safety of denosumab in reducing skeletal-related events (SRE) in patients with bone metastases.

Methods

A literature search using MEDLINE, EMBASE, Web of Science and The Cochrane Collaboration Library identified relevant controlled clinical trials up-to-March 14, 2012. Two independent reviewers assessed studies for inclusion, according to predetermined criteria, and extracted relevant data. The primary outcomes of interest were SRE, time to first on-study SRE, and overall survival. Secondary outcomes included pain, quality of life, bone turnover markers (BTM), and adverse events.

Results

Six controlled trials including 6142 patients were analyzed. Compared to zoledronic acid, denosumab had lower incidence of SRE with a risk ratio (RR) of 0.84 (95% confidence intervals (CI) 0.80–0.88), delayed the onset of first on-study SRE (RR 0.83; 95% CI 0.75–0.90) and time to worsening of pain (RR 0.84; 95% CI 0.77–0.91). No difference was observed in overall survival with pooled hazard ratio of 0.98 (95% CI 0.90–1.0). For total adverse events, denosumab was similar to zoledronic acid (RR 0.97; 95% CI 0.89–1.0). No significant differences were observed in the frequency of osteonecrosis of the jaw (RR 1.4; 95% CI 0.92–2.1). Patients on denosumab had a greater risk of developing hypocalcemia (RR 1.9; 95% CI 1.6–2.3).

Conclusions

Denosumab was more effective than zoledronic acid in reducing the incidence of SRE, and delayed the time to SRE. No differences were found between denosumab and zoledronic acid in reducing overall mortality, or in the frequency of overall adverse events.     

参麦注射液对阿霉素所致大鼠心肌损伤保护作用的实验研究

目的　观察参麦注射液 (SMI)对阿霉素 (ADM )诱导大鼠心肌损伤的保护作用和抗氧化作用。方法　选用ADM诱导大鼠心肌损伤模型。SD大鼠 60只 ,随机分为 3个组 ,每组 2 0只 ,分别为正常组、治疗组、对照组。正常组 :实验第 1～ 9天注射生理盐水 ,每天 3ml/kg ,1次 /天。治疗组 :实验第 1～ 9天注射参麦注射液 ,每天 3ml/kg ,1次 /天 ,第 4天注射阿霉素 ,隔天 1次 ,连用 3次 ,用生理盐水配置成 1mg/ml,每次 3mg/kg。对照组实验 1～ 9天注射生理盐水 ,每天 3ml/kg ,1次 /天。第 4天注射阿霉素 ,以后隔天 1次 ,连用 3次 ,用生理盐水配置成 1mg/ml,每次 3mg/kg。到期测定血丙二醛 (MDA )含量和超氧化物歧化酶(SOD )活性 ,并进行心肌病理检查。结果　对照组MDA水平明显高于治疗组 ,对照组SOD水平则显著低于治疗组 ,即加用SMI可提高SOD活性 ,降低MDA含量。SMI能明显减轻大鼠心肌损伤 ,对照组与治疗组比较 ,治疗组心肌损伤明显减轻 ,治疗组与正常组比较无显著性差异。参麦注射液有抗氧化作用 ,与对照组比较 ,血SOD水平升高 ,MDA水平降低 ,心肌病理计分下降。结论参麦注射液有抗氧化作用和对阿霉素所引起的心脏毒性具有保护作用 ,为临床寻找有效的阿霉素所致心肌损伤保护药物提供良好的客观依据 ,值得临床推广应用     

体内诱导艾氏腹水瘤细胞的耐药性研究

肿瘤细胞耐药性的存在是临床化疗失败的主要原因之一。本实验在小鼠体内用阿霉素（ADR）诱导艾氏腹水瘤细胞（EHR）的耐药性，探讨细胞产生耐药性的机理。HPLC法测定细胞内药物浓度．结果表明耐药细胞─—EHR/ADR细胞内ADR积聚低于EHR细胞，而对ADR外排快于EHR细胞；异博定（VER）增加EHR／ADR细胞对ADR的摄取并阻滞其外排．而对EHR影响不大，揭示EHR／ADR细胞具有MDR特性。     

Oxygen for relief of dyspnoea in mildly- or non-hypoxaemic patients with cancer: a systematic review and meta-analysis

The aim of this study was to determine the efficacy of palliative oxygen for relief of dyspnoea in cancer patients. MEDLINE and EMBASE were searched for randomised controlled trials, comparing oxygen and medical air in cancer patients not qualifying for home oxygen therapy. Abstracts were reviewed and studies were selected using Cochrane methodology. The included studies provided oxygen at rest or during a 6-min walk. The primary outcome was dyspnoea. Standardised mean differences (SMDs) were used to combine scores. Five studies were identified; one was excluded from meta-analysis due to data presentation. Individual patient data were obtained from the authors of the three of the four remaining studies (one each from England, Australia, and the United States). A total of 134 patients were included in the meta-analysis. Oxygen failed to improve dyspnoea in mildly- or non-hypoxaemic cancer patients (SMD=-0.09, 95% confidence interval -0.22 to 0.04; P=0.16). Results were stable to a sensitivity analysis, excluding studies requiring the use of imputed quantities. In this small meta-analysis, oxygen did not provide symptomatic benefit for cancer patients with refractory dyspnoea, who would not normally qualify for home oxygen therapy. Further study of the use of oxygen in this population is warranted given its widespread use.     

邻近腋窝的上皮样血管内皮瘤1例报道

We described a case of a 71-year-old woman with an epithelioid hemangioendothelioma (EHE) in her left axilla,a rare location which hasn't been reported yet. The patient suffered from numbness, pain and decreased muscle strength of her left upper extremity. Sonography revealed a hypoechoic mass surrounded the axillary artery and brachial artery. No obvious capsule was demonstrated. CT showed a soft-tissue mass with some calcifications and peripheral ring-like en-hancement. The MRI indicated a mass with mainly intermediate signal intensity on Tl-weighted imagine and intermediate signal intensity on T2-weighted imagine. The diagnosis was confirmed by histopathologic examination after surgery. There are some correlations of these imaging features with its histopathologic characters.     

GF方案与TP方案一线治疗晚期非小细胞肺癌的临床对照研究

Objective  

The aim of the study was to evaluate the efficacies of initial gemcitabine plus cisplatin (GP) and paclitaxel plus cisplatin (TP) 1st-line chemotherapies for advanced non-small cell lung cancer (NSCLC) and observe their side effects.     

鼻咽癌患者放射性骨坏死引起的正电子显像假阳性结果1例及文献复习

目的:探讨鼻咽癌(NPC)患者放射性骨坏死(osteoradionecrosis,ORN)引起正电子假阳性结果的原因及避免因此引发诊断错误的方法。方法:回顾性分析1例放疗后的鼻咽癌患者,行鼻咽部MRI及正电子显像后,再行组织病理学检查,对三种结果进行分析、比较。结果:MRI及正电子显像均诊断患者颅底区域肿瘤复发,组织病理学结果则显示鼻咽部病灶为放射性骨坏死。因此正电子扫描结果为假阳性结果。结论:鼻咽癌患者放疗后所致的放射性骨坏死容易引起正电子显像假阳性结果并可能引发不必要的治疗,因此NPC患者的正电子图像,对于可能的局限性肿瘤复发诊断,应该非常慎重。     

Bortezomib-related neuropathy may mask CNS relapse in multiple myeloma: A call for diligence

Background: Neuropathy is a common adverse effect of bortezomib. Isolated central nervous system (CNS) relapse in MM remains exceedingly rare and carries a dismal prognosis. We present an unusual case of bortezomib related neuropathy masking a CNS relapse of MM. Case presentation: A 57-year-old female was diagnosed with standard-risk MM with clinical and cytogenetic features not typically associated with CNS involvement. She was treated with 4 cycles of bortezomib/cyclophosphamide/dexamethasone (VCD) and achieved a VGPR, after which she underwent an autologous stem cell transplant (ASCT) followed by bortezomib maintenance. Six months after ASCT she developed symptoms suggestive of peripheral neuropathy which was attributed to bortezomib. However the symptoms persisted despite discontinuation of bortezomib. Imaging and cerebrospinal fluid analysis subsequently confirmed a CNS relapse. Discussion: CNS involvement in MM (CNS-MM) is uncommon and is considered an aggressive disease. Recently published literature has reported biomarkers with prognostic potential. However, isolated CNS relapse is even less common; an event which carries a very poor prognosis. Given the heterogeneous neurologic manifestations associated with MM, clinical suspicion may be masked by confounding factors such as bortezomib-based therapy. The disease may further remain incognito if the patient does not exhibit any of the high risk features and biomarkers associated with CNS involvement. Conclusion: In the era of proteasome inhibitor (PtdIns)/immunomodulator (IMID)-based therapy for MM which carries neurologic adverse effects, it is prudent to consider CNS relapse early. This case further highlights the need for more robust biomarkers to predict CNS relapse and use of newer novel agents which demonstrate potential for CNS penetration.