Tumor suppressor genes on frequently deleted chromosome 3p in nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is among the most common malignancies in southern China.Deletion of genomic DNA,which occurs during the complex pathogenesis process for NPC,represents a pivotal mechanism in the inactivation of tumor suppressor genes (TSGs).In many circumstances,loss of TSGs can be detected as diagnostic and prognostic markers in cancer.The short arm of chromosome 3 (3p) is a frequently deleted chromosomal region in NPC,with 3p21.1-21.2 and 3p25.2-26.1 being the most frequently deleted minimal regions.In recent years,our research group and others have focused on the identification and characterization of novel target TSGs at 3p,such as RASSF1A,BLU,RBMS3,and CHL1,in the development and progression of NPC.In this review,we summarize recent findings of TSGs at 3p and discuss some of these genes in detail.A better understanding of TSGs at 3p will significantly improve our understanding of NPC pathogenesis,diagnosis,and treatment.

Hepatocellular carcinoma mouse models:Hepatitis B virusassociatedhepatocarcinogenesis and haploinsufficienttumor suppressor genes

The multifactorial and multistage pathogenesis of hepatocellular carcinoma(HCC)has fascinated a wide spectrum of scientists for decades.While a number of major risk factors have been identified,their mechanistic roles in hepatocarcinogenesis still need to be elucidated.Many tumor suppressor genes(TSGs)have been identified as being involved in HCC.These TSGs can be classified into two groups depending on the situation with respect to allelic mutation/loss in the tumors:the recessive TSGs with two required mutated alleles and the haploinsufficient TSGs with one required mutated allele.Hepatitis B virus(HBV)is one of the most important risk factors associated with HCC.Although mice cannot be infected with HBV due to the narrow host range of HBV and the lack of a proper receptor,one advantage of mouse models for HBV/HCC research is the numerous and powerfulgenetic tools that help investigate the phenotypic effects of viral proteins and allow the dissection of the dose-dependent action of TSGs.Here,we mainly focus on the application of mouse models in relation to HBV-associated HCC and on TSGs that act either in a recessive or in a haploinsufficient manner.Discoveries obtained using mouse models will have a great impact on HCC translational medicine.

Characterization of six tumorsuppressor genes and microsatellite instability in hepatocellular carcinomain southern African blacks

AIM To analyse cumulative loss of heterozygosity (LOH) of chromosomal regions and tumor suppressor genes in hepatocellular carcinomas (HCCs) from 20 southern African blacks. METHODS p53, RB1, BRCA1, BRCA2, WT1 and E cadherin genes were analysed for LOH, and p53 gene was also analysed for the codon 249 mutation, in tumor and adjacent non tumorous liver tissues using molecular techniques and 10 polymorphic microsatellite markers. RESULTS p53 codon 249 mutation was found in 25% of the subjects, as was expected, because many patients were from Mozambique, a country with high aflatoxin B 1 exposure. LOH was found at the RB1, BRCA2 and WT1 loci in 20%(4/*!20) of the HCCs, supporting a possible role of these genes in HCC. No LOH was evident in any of the remaining genes. Reports of mutations of p53 and RB1 genes in combination, described in other populations, were not confirmed in this study. Change in microsatellite repeat number was noted at 9/*!10 microsatellite loci in different HCCs, and changes at two or more loci were detected in 15%(3/*!20) of subjects. CONCLUSION We propose that microsatellite/genomic instability may play a role in the pathogenesis of a subset of HCCs in black Africans.

Promoter methylation of tumor suppressor genes in esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma(ESCC) is a prevalent and fatal cancer in China and other Asian countries.Epigenetic silencing of key tumor suppressor genes(TSGs) is critical to ESCC initiation and progression.Recently,many novel TSGs silenced by promoter methylation have been identified in ESCC,and these genes further serve as potential tumor markers for high-risk group stratification,early detection,and prognosis prediction.This review summarizes recent discoveries on aberrant promoter methylation of TSGs in ESCC,providing better understanding of the role of disrupted epigenetic regulation in tumorigenesis and insight into diagnostic and prognostic biomarkers for this malignancy.

EXPRESSION OF NM23-H1 GENE PRODUCT IN NASOPHARYNGEAL CARCINOMA AND ITS CLINICAL SIGNIFICANCE

Objective: The nm23 gene is one of the tumor metastatic suppressor genes. The expression of nm23H1 has been reported to be inversely associated with metastatic potentiality in a number of human carcinomas, including breast, colorectal, gastric, hepatocellular and gallbladder carcinomas. In this study, the immunohistochemical staining of nm23H1 protein in human nasopharyngeal carcinoma (NPC) was examined, and the relationship between nm23H1 and both metastasis and prognosis of patients with NPC was also investigated. Methods: Routine LSAB immunohistochemistry with the nm23H1 monoclonal murine antibody was employed to study the expression of nm23H1 protein in 95 paraffinembedded specimens of NPC treated at our hospital. The clinical pathologic data and results of followup were also retrieved. Comparisons between patients with and without expression of nm23H1 protein with respect to metastasis, locoregional recurrence and survival were performed using Log rank test. Multivariate prognostic analyses were performed by using Cox's regression model. Results: Nm23H1 negative expressive tumors were associated with a higher incidence of lymphnode metastasis (86.7%) than those of nm23H1 positive (48.6%, P<0.01). Nm23H1 negative expressive tumors were associated with a high incidence of recurrence and distant metastasis after radiotherapy (P<0.05). A significant association was found between expression of nm23H1 and prognosis (P<0.01). The expression of nm23H1 indicated favorable prognosis. Conclusion: It was suggested that nm23 H1 negative expression was significantly associated with lymphnode metastasis, recurrence and distant metastasis. Nm23H1 may have value for predicting the prognosis of NPC.

Effect of hepatitis C virus infection on expression of several cancer-associated gene products in hepatocellular carcinoma

AIM To study hepatocarcinogenesis of hepatitis C virus (HCV). METHODS Expression of HCV antigens (CP10, NS3 and NS5) and several cancer associated gene products (ras p21, c myc, c erbB 2, mutated p53 and p16 protein) in the tissues of hepatocellular carcinoma (HCC, n =46) and its surrounding liver tissue were studied by the ABC (avidin biotin complex) immunohistochemical method. The effect of HCV infection on expression of those gene products in HCC was analyzed by comparing HCV antigen positive group with HCV antigen negative group. RESULTS Positive immunostaining with one, two or three HCV antigens was found in 20 (43 5%) cases, with either of two or three HCV antigens in 16 (34 8%) cases, and with three HCV antigens in 9 (19 6%) cases. Deletion rate of p16 protein expression in HCC with positive HCV antigen (80%, 16/20) was significantly higher than that in HCC with negative HCV antigen. Whereas no significant difference of the other gene product expression was observed between the two groups. CONCLUSION HCV appears related to about one third of cases of HCC in Chongqing, the southwest of China, and it may be involved in hepatocarcinogenesis by inhibiting the function of p16 gene, which acts as a negative regulator of cell cycle.

NDRG2 gene copy number is not altered in colorectal carcinoma

AIM To investigate if the down-regulation of N-myc Downstream Regulated Gene 2(NDRG2) expression in colorectal carcinoma(CRC) is due to loss of the NDRG2 allele(s).METHODS The following were investigated in the human colorectal cancer cell lines DLD-1, Lo Vo and SW-480: NDRG2 mRNA expression levels using quantitative reverse transcriptionpolymerase chain reaction(qRT-PCR); interaction of the MYC gene-regulatory protein with the NDRG2 promoter using chromatin immunoprecipitation; and NDRG2 promoter methylation using bisulfite sequencing.Furthermore, we performed qPCR to analyse the copy numbers of NDRG2 and MYC genes in the above three cell lines, 8 normal colorectal tissue samples and 40 CRC tissue samples.RESULTS As expected, NDRG2 mRNA levels were low in the three colorectal cancer cell lines, compared to normal colon.Endogenous MYC protein interacted with the NDRG2 core promoter in all three cell lines.In addition, the NDRG2 promoter was heavily methylated in these cell lines, suggesting an epigenetic regulatory mechanism.Unaltered gene copy numbers of NDRG2 were observed in the three cell lines.In the colorectal tissues, one normal and three CRC samples showed partial or complete loss of one NDRG2 allele.In contrast, the MYC gene was amplified in one cell line and in more than 40% of the CRC cases.CONCLUSION Our study suggests that the reduction in NDRG2 expression observed in CRC is due to transcriptional repression by MYC and promoter methylation, and is not due to allelic loss.

Aberrant methylation of SPARC in human hepatocellular carcinoma and its clinical implication

AIM:To investigate the methylation status of secreted protein acidic and rich in cysteine(SPARC) in human hepatocellular carcinoma(HCC) and evaluate its clinical implication.METHODS:The methylation status of SPARC was analyzed in one HCC cell line(SMMC-7721) and 60 pairs of HCC and corresponding nontumorous tissues by methylation-specific polymerase chain reaction and bisulfite sequencing.The expression of SPARC mRNA and protein were examined by reverse transcription polymerase chain reaction and immunohistochemistry,respectively.The correlations between the methylation status and the gene expression,the clinicopathological parameters,as well as the prognosis after surgery were analyzed.RESULTS:In the SMMC-7721 cell line,the loss of SPARC expression was correlated with the aberrant methylation and could be reactivated by the demethylating agent 5-aza-2'-deoxycytidine.Methylation frequency of SPARC in HCC was significantly higher than that in the corresponding nontumorous tissues(45/60 vs 7/60,P < 0.001),and it was correlated with the pathological classification(P = 0.019).The downregulation of the SPARC mRNA expression in HCC was correlated with the SPARC methylation(P = 0.040).The patients with methylated SPARC had a poorer overall survival than those without methylated SPARC(28.0 mo vs 41.0 mo,P = 0.043).CONCLUSION:Aberrant methylation is an important mechanism for SPARC inactivation in HCC and SPARC methylation may be a promising biomarker for the diagnosis and prognosis of HCC.

Inhibitory effect of IGF-Ⅱ antisense RNA on malignant phenotype of hepatocellular carcinoma

INIRODUCTIONAccording to the therapeutic effect and strategy ofantisense RNA for hepatoccllular carcinoma(HCC),we have specifically synthesized partialcDNA of human insulin-like growth factor Ⅱ(IGF-Ⅱ)and constructed IGF-Ⅱ cDNA antisenseeukaryotic expression vector.The constructedvector was introduced into hepatoma cell lineSMMC-7721 to block the intrinsic IGF-Ⅱexpression.The biological behavior changes ofhepatoma cells were observed.All these

MicroRNA and esophageal carcinoma

Objective：An abundant class of non-coding small RNA molecules, 21-25 nucleotide in length, are widely found in animals and plants and named microRNA （miRNA）. MiRNAs are highly evolutionarily conserved, expressing in specific tissue and timing, and negatively regulate the gene expressions at the posttranscriptional level,and subsequently control crucial physiological processes such as metabolism, amplification, differentiation, development and apoptosis, Therefore, miRNAs could provide an access to many human diseases in theory. Recent evidence demonstrates that miRNAs play an important role in the initiation and progression of human cancer, mainly by interrupting the cell cycle at the cellular level and by interacting with signaling The expression profiling of miRNAs can be used as a tool of diagnosis, staging, prognosis and biotherapy of some tumors, as has already been proven to have superiority to mRNA, in the categorization of tumors. This review focuses on the genesis, mechanism of action of miRNA and its relationship to tumors, detection methods and its potential effect on the diagnosis, staging, and biotherapy in esophageal carcinoma.

Behind the curtain of non-coding RNAs; long non-coding RNAs regulating hepatocarcinogenesis

Hepatocellular carcinoma(HCC) is one of the most common and aggressive cancers worldwide. HCC is the fifth common malignancy in the world and the second leading cause of cancer death in Asia. Long non-coding RNAs(lncRNAs) are RNAs with a length greater than 200 nucleotides that do not encode proteins. lncRNAs can regulate gene expression and protein synthesis in several ways by interacting with DNA, RNA and proteins in a sequence specific manner. They could regulate cellular and developmental processes through either gene inhibition or gene activation. Many studies have shown that dysregulation of lncRNAs is related to many human diseases such as cardiovascular diseases, genetic disorders, neurological diseases, immune mediated disorders and cancers. However, the study of lncRNAs is challenging as they are poorly conserved between species, their expression levels aren't as high as that of m RNAs and have great interpatient variations. The study of lncRNAs expression in cancers have been a breakthrough as it unveils potential biomarkers and drug targets for cancer therapy and helps understand the mechanism of pathogenesis. This review discusses many long non-coding RNAs and their contribution in HCC, their role in development, metastasis, and prognosis of HCC and how to regulate and target these lncRNAs as a therapeutic tool in HCC treatment in the future.

ISOLATION OF TUMOR DIFERENTIALLY EXPRESSED GENES BY MIXING PROBES LIBRARY SCREEN

Objective: This study was designed to clone candidate tumor suppressor genes down-expressed in Nasopharyngeal Carcinoma (NPC). Methods: Differentially expressed cDNA fragments (AF152605 and AF091517) were labeled by PCR, and Northern blot was used to confirmed transcript length of these genes. Skeleton muscle cDNA library was screened with PCR-labeled probe mixture. Results: 23 positive independent and overlapping positive clones were obtained. By sequencing the positive clones directly, three novel genes (Genbank accession number: AF179285, AF170307 and AF194971), with transcripts of 2.1 Kb, 1.1 Kb and 1.4 Kb respectively, were isolated successfully. Conclusions: Library screening using PCR-labeled probes mixture is an efficient method to get full-length cDNA from multi-cDNA fragment simultaneously and quickly.

Detailed Deletion Mapping of Chromosome 9p21-22 in Nasopharyngeal Carcinoma

Objective: To further refine the extent of deletion on chromosome 9p21-22 in nasopharyngeal carcinoma (NPC) and provide evidence for discovering new tumor suppressor gene. Methods: Loss of heterozygosity (LOH) on chromosome 9p21-22 was analyzed in 25 paired blood and tumor samples by using 11 high-density microsatellite polymorphic markers. Results: 17 of 25 cases (68.0%) showed LOH at one or more loci. Higher frequencies of LOH were found at four loci: D9S161 (35.0%), D9S1678 (31.5%), D9S263 (33.3%) and D9S1853 (33.3%), where 6 cases had a contiguous stretch of allelic loss. Conclusion: The minimal common region of deletion might be defined between D9S161 and D9S1853 (estimated about 2.7 cM in extent) at 9p21.1, suggesting that inactivation of one or more tumor suppressor genes located in this region may be an important step in NPC.

食管鳞癌患者血清中lncRNA-TUSC7、lncRNA-UCA1表达与血管生成拟态的关系及意义

目的探讨食管鳞状细胞癌(ESCC)患者血清长链非编码肿瘤抑制候选基因-7(lncRNA-TUSC7)、长链非编码尿路上皮癌相关基因1(lncRNA-UCA1)表达与血管生成拟态(VM)的关系及意义。方法回顾性分析2020年3月至2021年12月经该院确诊为ESCC的133例患者,按照是否形成VM将其分为有VM组76例及无VM组57例,实时荧光定量聚合酶链反应(qPCR)检测两组患者血清lncRNA-TUSC7、lncRNA-UCA1表达;分析lncRNA-TUSC7、lncRNA-UCA1表达与ESCC患者不同临床参数之间的关系;Spearman相关系数分析lncRNA-TUSC7、lncRNA-UCA1表达与VM生成之间的相关性;受试者工作特征曲线(ROC曲线)分析联合lncRNA-TUSC7、lncRNA-UCA1检测对ESCC患者形成VM的预测效能。结果相比于无VM组,VM组患者lncRNA-TUSC7表达显著降低,而lncRNA-UCA1表达显著增高,差异有统计学意义(P<0.05);lncRNA-TUSC7与ESCC患者肿瘤分化程度、临床分期、淋巴结转移情况及是否发生VM具有密切联系(均P<0.05);lncRNA-UCA1与ESCC患者肿瘤分化程度、临床分期、淋巴结转移情况、浸润程度及是否发生VM具有密切联系(均P<0.05);Spearman相关系数显示,lncRNA-TUSC7与VM生成之间呈负相关(r=-0.782,P<0.001),而lncRNA-UCA1与VM生成之间呈正相关(r=0.766,P<0.001)。ROC曲线显示lncRNA-TUSC7、lncRNA-UCA1联合检测的曲线下面积显著高于单一检测(Z=2.428,P<0.05),灵敏度为89.40%,特异度为83.20%,对ESCC发生VM具有较高的诊断效能。结论通过定时监测ESCC患者lncRNA-TUSC7、lncRNA-UCA1表达能够对其是否合并VM做出有效评估,并对及时采取治疗措施预防奠定了可信的生物标志物基础,同时也为日后靶向治疗ESCC合并VM患者提供了可能的治疗靶点,具有较为深远的临床意义。

抑癌基因SPRED2在肾透明细胞癌中的表达及意义

目的在肾透明细胞癌进展过程中,初步探讨抑癌基因SPRED2所起到的生理学作用。方法收集遵义医科大学附属医院泌尿外科近年接受手术的肾透明细胞癌患者的癌组织及癌旁组织标本,另取材于良性肾脏病变组织作为正常肾组织对照。采用免疫组织化学法及Western-blot,分别检测SPRED2及LC3蛋白在肾透明细胞癌组织、癌旁组织以及正常肾组织中的表达情况,并将各组织中两种蛋白的具体表达水平进行两两比较。结果通过免疫组化染色(n=10),初步确定SPRED2及LC3蛋白在组织中的表达定位于细胞膜和胞浆,以细胞膜为主。Western-blot结果显示(n=9),SPRED2在癌组织、癌旁组织及正常肾组织中的表达水平分别为(0.52±0.24)、(0.86±0.30)及(1.47±0.55)。SPRED2在癌组织中的表达含量显著低于癌旁组织(P<0.05),在癌旁组织中的表达含量明显低于正常肾组织(P<0.01),差异均有统计学意义。LC3在癌组织、癌旁组织及正常肾组织中的表达水平分别为(1.34±0.40)、(0.72±0.32)及(0.33±0.12)。LC3在正常肾组织中的表达含量明显低于癌旁组织(P<0.01),在癌旁组织中的表达含量明显低于癌组织(P<0.05),差异均有统计学意义。结论SPRED2在肾透明细胞癌组织中的表达含量显著降低,并低于癌旁组织及正常肾组织,其在肿瘤进程中可能发挥抑制作用。

HBV相关肝细胞癌抑癌基因甲基化异常及机制的研究进展

肝细胞癌(HCC)的死亡率位居世界第三,其早期诊断及晚期治疗手段有限。由于甲胎蛋白(AFP)在肝癌早期临床诊断的敏感度较低,以及人们对该病自身及生活方式认识不足,这种癌症的发病率仍在上升。乙型肝炎病毒(HBV)感染作为我国公认的导致肝脏细胞发生癌变的主要危险因素,其可能会加快基因甲基化的进程,继而导致肝细胞癌的发生。DNA甲基化及其诱导的表观遗传学改变,由于其潜在的可逆性,为寻找HCC的新型生物标志物和治疗提供了新的途径。这些抑癌基因甲基化异常在HBV相关HCC发展中的机制仍未被阐明,进一步了解HBV相关HCC表观遗传学的新分子靶点对HCC的诊断、治疗和预防具有重要意义。本文就DNA甲基化介导HBV相关肝细胞癌中抑癌基因甲基化异常及机制进行综述,为攻克肝癌治疗的难点提供新的思路。

子宫内膜癌组织中Ki-67、p16蛋白的表达及其对手术治疗预后的评估价值

目的 观察子宫内膜癌(EC)组织中增殖细胞核抗原-67(Ki-67)、抑癌基因p16蛋白表达,分析EC组织中Ki-67、p16蛋白表达对手术治疗预后的评估价值。方法 选择137例实施手术治疗的EC患者作为研究对象,收集患者的EC组织,检测Ki-67、p16在EC组织中的表达,随访2年,评估患者预后(复发、转移发生)情况,比较不同预后EC患者基线资料、实验室指标,重点分析EC患者组织中Ki-67、p16蛋白表达对手术治疗预后的预测。结果 随访2年,137例EC患者中17例复发,4例转移,预后不良发生率为15.33%(21/137)。经Logistic回归分析结果显示,国际妇产科协会(FIGO)分期高、Ki-67表达高可能是EC患者淋巴结转移的风险因子(OR>1,P<0.05),p16表达高可能是EC患者手术治疗预后的保护因子(OR<1,P<0.05)。绘制ROC曲线图,结果显示,Ki-67、p16蛋白表达预测EC患者手术治疗预后不良的AUC分别为0.833、0.827,均有一定预测价值;绘制决策曲线结果显示,在阈值0.2~1.0范围内,联合子宫内膜癌患者组织中Ki-67、p16蛋白表达预测EC患者手术治疗预后不良的净受益率优于单独某一指标,且在高风险阈值0.0~1.0内的净受益率始终大于0,始终有临床意义,净受益率最大值为0.153。结论 子宫内膜癌组织中Ki-67、p16蛋白表达与手术治疗预后有关,用于预测预后不良具有一定的价值,且联合预测获得的净受益率更高。

鼻咽癌分子标志物研究

鼻咽癌严重危害人类健康,寻找其早期诊断及预后相关的分子标志物迫在眉睫.在总结本课题组运用基因组学、转录组学、蛋白质组学和组织微阵列等高通量技术对不同分化阶段、不同组织类型和不同临床分期的鼻咽癌标本进行大规模筛选工作的基础上,结合近年国际上有关进展,初步构建了鼻咽癌不同发病阶段的分子靶标系统:a.证实SPLUNC1、p16、EBER-1、p27、RASSF1A和CDH13是鼻咽癌早期诊断的理想分子靶标;b.鼻咽癌上调基因RB1,STMN1和DSP及下调基因SERPINB6,AGTRL1和SYTL2的分类预测模型是区分正常鼻咽上皮和鼻咽癌的分子靶标;c.NGX6、Ezrin、LTF、OPN、THY1和Tiam-1是鼻咽癌侵袭与转移预测的候选分子靶标;d.Cyclin D1、Survivin和HPA是与鼻咽癌预后相关的候选分子标志物;e.证实Bcl-2、EGFR和Ki67是预测鼻咽癌放疗敏感与否的候选分子靶标;f.SAA和cox-2是监测鼻咽癌复发的候选分子标志物;g.发现BRD7、NGX6、NOR1和UBAP1的6个SNP改变是鼻咽癌遗传易感风险因子;h.建立了由139个基因组成的鼻咽癌不同临床分期分子靶标系统.这些在大样本基础上的分子靶标筛选为鼻咽癌分子分型研究奠定了重要工作基础.

食管癌中抑癌基因PTEN的表达及临床意义

目的探讨抑癌基因PTEN在食管癌中的表达及临床意义。方法用免疫组织化学方法检测80例食管癌及其相应的手术远端正常食管组织中PTEN蛋白的表达水平。结果PTEN在食管鳞癌中的表达率明显低于癌旁正常食管黏膜组织(P<0.01),而且PTEN蛋白表达与肿瘤分化程度、浸润深度、淋巴结转移相关(P<0.01)。结论从蛋白水平证明PTEN基因表达缺失或突变在食管鳞癌的发生发展中可能起重要作用,PTEN蛋白表达的检测可作为临床治疗和判断预后的依据。

甲状腺乳头状癌患者血清、癌组织中p53、Fas、TNF-α和Cyclin E的表达及临床意义

目的:观察肿瘤抑制基因(p53)、细胞凋亡信号受体(Fas)、肿瘤坏死因子-α(TNF-α)和细胞周期素E(Cyclin E)在甲状腺乳头状癌患者血清及癌组织中的表达,探讨其与甲状腺乳头状癌临床病理特征的关系。方法:选取穿刺确诊为甲状腺乳头状癌的住院患者作为实验组(n=74)、同期体检健康人作为正常对照组(n=26)。两组均空腹抽取静脉血,实验组于术后留取癌组织、癌旁正常组织及术后7 d再次空腹抽取静脉血。采用酶联免疫法检测血清、癌旁正常组织及癌组织中p53、Fas、TNF-α和Cyclin E蛋白的含量;采用实时荧光定量法检测甲状腺乳头状癌组织及癌旁正常组织中p53、Fas、TNF-α和Cyclin E的基因表达水平;采用免疫组织化学方法检测甲状腺乳头状癌组织及癌旁正常组织中p53、Fas、TNF-α和Cyclin E的蛋白阳性表达强度;分析其表达与甲状腺乳头状癌的临床分期、病理类型及有无淋巴结转移的关系。结果:甲状腺乳头状癌患者血清中p53、Fas和TNF-α的蛋白含量明显低于正常对照组,Cyclin E的蛋白含量明显高于正常对照组,差异均有统计学意义(P<0.01);甲状腺乳头状癌患者癌组织中p53、Fas和TNF-α的蛋白含量、蛋白阳性表达强度及基因表达水平明显低于癌旁正常组织,Cyclin E的蛋白含量、蛋白阳性表达强度及基因表达水平明显高于癌旁正常组织,差异亦均有统计学意义(P<0.05)。结论:p53、Fas和TNF-α在甲状腺乳头状癌组织中表达水平下调和Cyclin E表达水平上调,可能在甲状腺乳头状癌浸润和转移中起重要作用。四者的联合检测可作为早期诊断甲状腺乳头状癌的标记物,提高甲状腺乳头状癌的早期诊断率。