基于TCGA数据库分析甲状腺癌基因表达谱

为分析甲状腺癌基因表达谱,筛选疾病相关的基因标志物。基于肿瘤基因组图谱(TCGA)数据库中的甲状腺癌基因表达数据,运用R/Bioconductor统计平台进行数据处理与统计学分析。分别应用edgeR算法和limma算法选取肿瘤组织与对照组间倍数改变 > 2,P< 0.05的基因作为差异基因;进一步运用Medcalc统计软件进行受试者工作特征曲线(ROC)分析,鉴定出有诊断标志物潜在应用价值的基因标志物。通过两种运算方法筛选出甲状腺癌组织中存在着1 945个差异基因(上调基因1 033个,下调基因912个);根据差异倍数进一步鉴定出11个基因在肿瘤组织中表达上调,且对鉴别肿瘤组与对照组有较好的应用价值。本研究分析了TCGA中的甲状腺癌表达谱数据,鉴定出了与疾病诊断显著相关的差异表达基因,能够为探索疾病发生发展机制及寻找新型分子标志物提供依据。     

超声检查联合MMP-2、MMP-9水平检测对甲状腺癌的诊断价值

目的:探讨超声检查联合基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)水平检测对甲状腺癌的诊断价值。方法:选取2014年6月-2016年6月我院收治的480例甲状腺结节患者作为研究对象,根据患者病情分为良性结节患者412例(良性结节组)和甲状腺癌患者68例(甲状腺癌组)。对所有患者进行超声检查与MMP-2、MMP-9水平检测,比较两组MMP-2、MMP-9水平,并比较超声检查与超声联合MMP-2、MMP-9水平检测对甲状腺癌的诊断价值。结果:甲状腺癌组MMP-2、MMP-9水平均显著高于良性结节组(P0.05),且甲状腺癌组超声弹性图像评分多为3~4分,良性结节组则多为0~2分,两组超声弹性成像评分所占比例比较差异有统计学意义(P0.05);超声联合MMP-2、MMP-9诊断良性甲状腺结节的阴性率和甲状腺癌的阳性率均高于超声诊断,差异有统计学意义(P0.05);超声联合MMP-2、MMP-9的灵敏性、特异性、准确性分别为89.7%、85.2%、85.8%,均显著高于超声诊断的76.5%、68.7%、69.8%,差异有统计学意义(P0.05)。结论:超声检查联合MMP-2、MMP-9水平检测能够有效鉴别甲状腺癌,其灵敏性、特异性、准确性均较高,值得在临床上推广。     

胰腺癌相关肿瘤标志物研究进展

胰腺癌起病隐匿,进展快,预后差,发病率约等于死亡率。胰腺癌死亡率高的原因有发病机制不明,缺乏有效的早期诊断和预后的肿瘤标志物,进展期相关治疗效果不理想。近年来在血清标志物、基因标志物、表观遗传学标志物等分子生物技术及生物信息学方面的发展为胰腺癌的诊断,尤其是早期诊断、评估预后和监测早期复发提供了新的途径。本文就近期胰腺癌相关肿瘤标志物的研究进展作一综述。     

BRAF~(T1799A)突变、RET/PTC重排对术前诊断甲状腺乳头状癌的作用

目的:探讨术前超声引导下细针抽吸细胞学检查(US-FNAB)联合BRAFT1799A突变、RET/PTC1及RET/PTC3重排对诊断甲状腺乳头状癌(PTC)的特异性及敏感性,为临床术前准确诊断PTC选择适用的分子标记物。方法:收集346个超声怀疑为甲状腺恶性结节的US-FNAB细胞标本及对应结节(152个)的术后新鲜组织,采用PCR分别扩增BRAFT1799A、RET/PTC1及RET/PTC3基因,产物经基因测序证实。结果:346个甲状腺术前穿刺的结节中,选择观察而未手术的结节192个,手术治疗152个,未接受手术建议的结节2个。术前US-FNAB的细胞标本中共检测到51个结节发生BRAFT1799A突变,其细胞学分类为36个恶性,11个可疑恶性,4个良性。该51个结节术后病理证实均为PTC。20个发生RET/PTC1重排,其术前细胞学结果为17个恶性,2个可疑恶性,1个滤泡性肿瘤或可疑滤泡性肿瘤,术后病理证实均为PTC。3个结节发生RET/PTC3重排,其术前细胞学结果为恶性,术后病理证实均为PTC。对45个术前US-FNAB标本检测BRAFT1799A突变阴性而术后病理证实为PTC的结节,将其对应结节的术中组织行该基因的检测,仅有1个结节的术后组织中检测到该突变。本研究中,术前US-FNAB联合多分子标志物的检测,将细胞学诊断PTC的敏感度由73.96%提高到92.71%。结论:术前US-FNAB联合多分子标志物的检测可提高其诊断PTC的敏感性及特异性,并有助于患者的个体化诊治。     

外泌体在结直肠癌肝转移中的研究进展

肝脏是结直肠癌最常见的转移部位之一,肝转移灶的发生和发展会直接导致结直肠癌患者生存期明显缩短,且现有的治疗策略总体效果欠佳,因此,寻找更为有效的诊断和预后的生物标志物及可干预的靶点成为改善结直肠癌患者预后的一项重要任务。外泌体在结直肠癌肝转移过程中起重要作用,可介导化疗耐药的产生,同时作为生物标志物在结直肠癌肝转移的诊断和预后方面也具有一定价值。外泌体研究为结直肠癌靶向治疗提供了分子基础。本文就外泌体在影响结直肠癌肝转移、促进治疗耐药以及为结直肠癌肝转移提供诊断及预后价值的研究进展进行综述。     

甲状腺多发结节伴甲状腺癌的诊治分析

目的分析甲状腺多发结节伴甲状腺癌的诊断和手术方式,以提高对甲状腺多发结节伴甲状腺癌的诊治水平。方法回顾性分析2013年2月~2014年2月我院诊治的98例甲状腺多发结节伴甲状腺癌患者的临床资料。结果在诊断中,CT诊断的准确率为76.58%,超声诊断的准确率为84.26%,两者联用的诊断准确率为92.17%。98例患者中,甲状腺多发结节伴发的乳头状癌88例,占89.79%;滤泡状癌8例,占8.16%;髓样癌2例,占2.04%。结论在甲状腺多发结节伴甲状腺癌的诊断中,超声、CT两者联用可提高诊断准确率;甲状腺结节多与良性疾病并发,应行结节冰冻病理切片,明确性质后确定手术方式,力求一期手术根治。     

长链非编码RNA表征及其在结直肠癌发生发展中的作用和临床意义

长非编码RNA（long non-coding RNAs, lncRNAs）是一类转录本长度大于200个核苷酸,不具有蛋白质编码功能的非编码RNA（non-coding RNA, ncRNA）。人类基因组中,ncRNA基因占比超过90%,数量远大于蛋白质编码基因。作为生物大分子,lncRNA具有特定的初级和高级结构,在基因表达调控等生物学进程中发挥着特有的功能。lncRNA数量多,结构各异,因此鉴定和表征新的lncRNA,探索其结构和功能,是当前基因研究领域的热点之一。在临床疾病机制研究中,大量结果表明,lncRNA与临床疾病发生发展,特别是肿瘤的发生发展具有密切的相关性。伴随着后基因组学时代基因鉴定和功能探索方法的不断进步,探索lncRNA在疾病发生中的功能及表达变化,深入解锁lncRNA在疾病发生中涉及的分子机制,将为疾病早期预防、诊断和预后提供有效参考。基于以上的研究大背景,本文对lncRNA的定义、基因鉴定的策略和方法,高级结构检测及其对应的生物学功能,以及lncRNA的分类进行了阐述;另一方面,基于lncRNA与肿瘤发生发展的密切关系,本文以经典抑癌基因p53为切入点,对多种p53相关的lncRNA在结直肠癌（colorectal cancer, CRC）发生发展中的作用进行了归纳小结,阐述了lncRNA在结直肠癌中的表达变化、涉及的分子互作机制和信号通路,对其作为分子标志物在临床中的应用潜力进行了评估。我们乐观地认为,作为生物分子标志物,lncRNA将为包括癌症在内的疾病治疗提供全新、精准和个性化的分子靶点。     

CD44V6和MMP-2在甲状腺肿瘤中的表达及其临床意义

目的:研究黏附分子CD44V6和基质金属蛋白酶-2(MMP-2)在甲状腺癌中的表达、相互关系及其与甲状腺癌侵袭转移的相关性.方法:采用SP免疫组化法检测114例甲状腺肿瘤组织中CD44V6和MMP-2的表达.结果:CD44V6和MMP-2在35例甲状腺乳头状癌(Papillary Thyroid Carcinoma,PTC)中阳性表达率分别为70.6%和73.5%,在41例甲状腺滤泡癌(Follicular Thyroid Carcinomas,FTC)中阳性表达率分别为70.7%和75.6%,均高于甲状腺腺瘤和结节性甲状腺肿组织中的表达,差异具有统计学意义(P＜0.05).在甲状腺癌组织中MMP-2和CD44V6的表达具有显著相关性(r=0.4828,P＜0.001).且两者表达与甲状腺癌的临床分期及有、无淋巴结转移显著相关.结论:CD44V6和MMP-2的表达与甲状腺癌分化程度、浸润和转移关系密切.CD44V6和MMP-2检测对甲状腺癌的诊断、分化程度、转移趋势和预后评估具有重要参考价值,是甲状腺癌侵袭、转移和预后判断的分子标志物.     

头颈部鳞癌生物标志物的预后作用

头颈部鳞癌(HNSCC)是世界上常见的恶性肿瘤之一。尽管现有治疗手段不断完善,HNSCC的5年生存率仍徘徊在50%。肿瘤生物标志物是由肿瘤细胞合成、释放或是宿主对肿瘤的反应而释放的物质。它有助于肿瘤的分子诊断、预后判断及疗效预测。因此生物标志物具有诊断、预后和预测三大作用。本文分别就与HNSCC相关的临床确定的和正在热研的,主要具有预后作用的生物标志物进行阐述。临床确定的标志物包括EBV和HPV。迄今为止众多生物标志物被研究且结果喜人。本文介绍的热研的标志物包括细胞周期调控、转录因子和信号传导三个方面。除了综述生物标志物预后作用的最新研究信息,还对研究中出现预后作用不一致的原因进行分析。分子细胞生物学的发展促使更多的生物标志物及潜在治疗靶点被发现。从预后到预测的发展是实施肿瘤个体化治疗的目标。以生物标志物为治疗靶点,有望改善HNSCC的预后,实现个体化精准治疗。     

分子诊断技术在乳腺癌检测中的最新进展

乳腺癌是一种严重危害女性健康的恶性肿瘤,对其致病基因的检测有助于肿瘤早期诊断、精准治疗及预后评估.本文总结了近年来乳腺癌相关的热点基因,并对相关基因的分子诊断技术、检测方法及应用进行了综述.首次评述了数字PCR方法用于乳腺癌分子检测的进展.全面对比不同分子诊断技术的差别与优缺点,为乳腺癌关键基因的检测提供指导建议与理论支持,并对未来发展趋势做出展望.     

Autoimmune Thyroid Disease: A Risk Factor for Thyroid Cancer

ObjectiveTo examine the relationship between clinical markers of autoimmune thyroid disease and the risk of thyroid cancer in patients with thyroid nodules.MethodsA retrospective cohort analysis was performed in a single clinical practice. In 2, 500 consecutive patients, fine-needle aspiration biopsy (FNAB) was performed on all 3, 658 ultrasonography-positive thyroid nodules that were ≥ 1.0 cm in diameter or ≥ 0.5 cm in diameter with ultrasound features suspicious for thyroid cancer. Serum concentrations of thyroglobulin antibodies (TgAb), thyroid peroxidase antibodies, and thyroid-stimulating hormone were measured before FNAB. Diagnosis of thyroid cancer was based on pathologic analysis of thyroidectomy tissue. Associations of thyroid cancer with the independent variables were determined by multivariate logistic regression analysis and reported as the adjusted odds ratio (OR) with the 95% confidence interval (CI).ResultsThere were 202 patients with malignant thyroid nodules, 51 patients with microscopic unsuspected thyroid cancer distal to the nodule under investigation (found at thyroidectomy), and 2, 247 patients with benign thyroid nodules. To evaluate the association of clinical markers for autoimmune thyroid disease with thyroid cancer, we included all 253 patients with thyroid cancer in the malignant cohort. Thyroid cancer was associated with elevated levels of TgAb (OR = 1.57; CI = 1.11 to 2.23) and age < 55 years (OR = 2.01; CI = 1.45 to 2.78), and a strong trend was demonstrated for association with male sex (OR = 1.45; CI = 0.99 to 2.12). Thyroid cancer was not associated with elevated levels of thyroid peroxidase antibodies.ConclusionIn patients who have thyroid nodules with indications for FNAB, elevated levels of TgAb are associated with thyroid cancer. (Endocr Pract. 2011;17: 201-209)     

Overview of Molecular Biomarkers for Enhancing the Management of Cytologically Indeterminate Thyroid Nodules and Thyroid Cancer

ObjectiveTo provide information on molecular bio markers that can help assess cytologically indeterminate thyroid nodules.MethodsPublished studies on immunohistologic, somatic mutation, gene expression classifier, microRNA, and thyrotropin receptor messenger RNA biomarkers are reviewed, and commercially available molecular test pan els are described.ResultsThyroid nodules are common, and clinical guidelines delineate an algorithmic approach including serum thyroid-stimulating hormone measurement, diagnostic ultrasound examination, and, when appropriate, fine-needle aspiration (FNA) biopsy for determination of a benign versus malignant status. In clinical practice, approximately 20% of FNA-derived cytology reports are classified as “indeterminate” or follicular nodules that do not fulfill either benign or malignant criteria. In this set ting, the actual risk for malignancy of a cytologically indeterminate nodule ranges from approximately 15% to 34%. Research describing molecular biomarkers from thyroid cancer tissue has been applied to FNA-derived thyroid nodule material. There is also a serum molecular marker that has been reported with goals similar to those for the FNA-derived molecular markers: to enhance the preoperative diagnosis of thyroid cancer and reduce the large number of patients who have a diagnostic surgical procedure for benign thyroid nodules.ConclusionProgress toward the foregoing goals has been made and continues to evolve with the recent appearance of molecular biomarker tests that can be selectively applied for further assessment of cytologically indeterminate thyroid nodules. (Endocr Pract. 2012;18:611-615)     

Diagnostic use of Molecular Markers In the Evaluation of Thyroid Nodules

ObjectiveTo describe the molecular markers thus far evaluated for use in the care of patients with clinically relevant thyroid nodules.MethodsWe review the currently available molecular tests that have been applied to patients with thyroid nodules.ResultsIn the United States, approximately 450 000 diagnostic fine-needle aspirates will be performed on patients with thyroid nodules this year in an effort to identify thyroid cancer. Unfortunately, this test is imprecise and, at times, inaccurate. Because of this, novel diagnostic testing modalities have been pursued, the most promising of which involve molecular analysis of thyroid tissue. Immunohistochemical staining, analysis for mutations and gene rearrangements, and microarray analysis have all been investigated with regard to their performance characteristics in targeted patient populations.ConclusionsMolecular tests to evaluate thyroid nodules demonstrate variable performance characteristics. Further evaluation of available and emerging molecular tests will necessarily rely on prospective real-world test validation in the clinical setting. (Endocr Pract. 2012;18: 796-802)     

超声造影在甲状腺结节鉴别诊断及良性结节微波消融治疗中的应用价值

摘要 目的：研究超声造影在甲状腺结节鉴别诊断及良性结节微波消融治疗中的应用价值。方法：选取2015年1月～2018年2月我院收治的甲状腺结节患者100例作为研究对象,所有纳入对象均进行超声造影检查,分析甲状腺结节的超声造影特征,并与病理诊断结果进行对照。此外,将甲状腺良性结节患者以随机抽签法分成超声造影组31例和常规超声组30例。超声造影组微波消融治疗前后均予以超声造影配合,常规超声组微波消融治疗前后均予以常规超声配合。比较两组治疗前后甲状腺结节造影情况以及术后1年结节复发情况。结果：甲状腺恶性结节增强强度为低增强、增强模式为不均匀、无环绕增强占比均高于良性结节（均P＜0.05）。以病理诊断为金标准,超声造影诊断恶性甲状腺结节的灵敏度为92.31%、特异度为78.69%、准确度为84.00%。治疗后超声造影组甲状腺结节最长径、体积均低于常规超声组（均P＜0.05）。超声造影组术后1年结节复发率为0.00%,低于常规超声组的16.67%（P＜0.05）。结论：超声造影应用于甲状腺结节鉴别诊断的价值较高,且结合微波消融治疗良性结节的效果明显,预后理想,值得临床推广应用。     

Molecular pathology and thyroid FNA

This review summarises molecular pathological techniques applicable to thyroid FNA. The molecular pathology of thyroid tumours is now fairly well understood. Molecular methods may be used as a rule‐in test for diagnosis of malignancy in thyroid nodules, eg BRAF V600E point mutation, use of a seven‐gene mutational panel (BRAF V600E, RAS genes, RET/PTC or PAX8/PPARG rearrangement), or as a comprehensive multigene next‐generation sequencing panel, eg ThyroSeq v2. Molecular methods can also be applied as rule‐out tests for malignancy in thyroid nodules, eg Afirma or ThyroSeq v2 or as markers of prognosis, eg TERT promoter mutation or other gene mutations including BRAF V600E, TP53 and AKT1, and as tests for newly defined tumour entities such as non‐invasive follicular thyroid neoplasm with papillary like nuclei, or as a molecular marker(s) for targeted therapies. This review describes practical examples of molecular techniques as applied to thyroid FNA in routine clinical practice and the value of molecular diagnostics in thyroid FNA. It describes the range of molecular abnormalities identified in thyroid nodules and thyroid cancers with some practical applications of molecular methods to diagnosis and prognosis of thyroid nodules and thyroid cancer.     

甲状腺再次手术治疗的临床分析

目的:探讨甲状腺再次手术的原因、手术方式的选择和手术效果以及患者的预后情况。方法:统计哈尔滨医科大学附属第二医院普外科2001年1月到2015年9月期间收治的1600例初次行甲状腺手术的患者,回顾分析其中175例再次行甲状腺手术患者的临床资料。结果:甲状腺再次手术采用双侧甲状腺次全切除术为92例,单侧甲状腺次全切除术为72例,甲状腺癌根治术为11例。甲状腺再次手术患者术后出现甲状腺功能减退、气管和喉返神经损伤、出血以及缺钙引起的手足抽搦等概率高,与首次手术比较差异有统计学意义(P0.05)。术后1年内对再次手术的患者进行随访,其中复发12例(病理确诊为甲状腺癌3例,结节性甲状腺肿9例),其他类型甲状腺疾病无复发。结论:甲状腺再次手术较初次手术难度较大,术中及术后并发症较多,再次手术应谨慎选择术式及术中精细操作。     

Diagnostic Use of Ultrasonography in Patients with Nodular Thyroid Disease

ObjectiveTo review the published reports pertaining to the diagnostic utility of ultrasonography for evaluation of thyroid nodules.MethodsVarious roles for diagnostic thyroid ultrasonography and screening ultrasound studies of the thyroid are discussed, and ultrasound characteristics of thyroid nodules and their association with malignant potential are described.ResultsIn two studies that correlated ultrasound findings with physical examination findings in patients with a solitary thyroid nodule detected by palpation, 16% of such patients had no corresponding nodule evident on ultrasonography, and 45% of such patients had an additional nodule detected by ultrasonography. Similarly, approximately 18% of patients with a palpable multinodular thyroid had no nodules larger than 1 cm in diameter on ultrasound studies. Thyroid nodules larger than 1 cm have been found by ultrasonography to be present in from 2 to almost 5% of the population with normal findings on examination of the thyroid. Use of screening ultrasound study of the thyroid has been suggested for patients with a history of childhood irradiation to the head and neck or a family history of thyroid cancer. Numerous investigations that have evaluated ultrasound features of thyroid nodules have suggested five characteristics as suggestive of malignant potential—hypoechogenicity, microcalcifications. irregular or microlobulated border, absent or irregular thick halo, and increased intranodular vascularity.ConclusionCorrelation of ultrasound and palpation findings will provide a comprehensive evaluation of nodular thyroid disease. Moreover, real-time ultrasonography facilitates characterization of features associated with an increased risk of a malignant lesion. High-resolution thyroid ultrasonography is a dynamic tool for endocrinologists. (Endocr Pract. 2004;10:246-252)     

Thyroid Nodule Evaluation and Management in Older Adults: A Review of Practical Considerations for Clinical Endocrinologists

ObjectiveContextualizing the evaluation of older adults with thyroid nodules is necessary to fully understand which management strategy is the most appropriate. Our goal was to summarize available clinical evidence to provide guidance in the care of older adults with thyroid nodules and highlight special considerations for thyroid nodule evaluation and management in this population.MethodsWe conducted a literature search of PubMed and Ovid MEDLINE from January 2000 to November 2020 to identify relevant peer-reviewed articles published in English. References from the included articles as well as articles identified by the authors were also reviewed.ResultsThe prevalence of thyroid nodules increases with age. Although thyroid nodules in older adults have a lower risk of malignancy, identified cancers are more likely to be of high-risk histology. The goals of thyroid nodule evaluation and the tools used for diagnosis are similar for older and younger patients with thyroid nodules. However, limited evidence exists regarding thyroid nodule evaluation and management to guide personalized decision making in the geriatric population.ConclusionConsidering patient context is significant in the diagnosis and management of thyroid nodules in older adults. When making management decisions in this population, it is essential to carefully weigh the risks and benefits of thyroid nodule diagnosis and treatment, in view of older adults’ higher prevalence of high-risk thyroid cancer as well as increased risk for multimorbidity, functional and cognitive decline, and treatment complications.