Pathology and DNA Cytophotometry of Small Hepatocellular Carcinoma with a Nodule-in-nodule Appearance--Evidence for Stepwise Progression of Hepatocellular Carcinoma

Among 92 surgically resected human hepatocellular carcinomas(HCCs) 3cm in diameter, 23 tumors (25%) grossly showed a nodule-in-noduleappearance indicating stepwise progression of HCC. The centralnodules showed destructive growth of HCC, which was less differentiatedthan the surrounding area histologically, while the surroundingarea showed growth of very-welldifferentiated HCC with no, oronly minimal, destruction of the underlying liver structures.Previously, we proposed the term "early HCC" for HCCs withoutdefinite destructive growth, and the nodule-in-nodule lesionsdescribed here are considered to be in the transitional stagefrom early HCC to advanced HCC, and are therefore named earlyadvanced HCC (eAd HCC). DNA cytophotometry was performed in12 cases of eAd HCC, in which the early HCC component, advancedHCC component and non-tumorous liver tissue showing chronichepatitis or cirrhosis were analyzed separately. The early HCCcomponent showed a diploid pattern in eight of the 12 cases.The advanced HCC component showed an aneuploid peak in sevencases, and in three of these the peak was detected only in theadvanced HCC component and not in the early HCC component. Themean nuclear DNA content was significantly increased from nontumorousliver to the early HCC component and from the early HCC componentto the advanced HCC component. Polyploid cells containing morethan 4.8C DNA were exceptional in non-tumorous liver, but weredetectable in the early HCC component and increased in numberin the advanced HCC component. These findings suggest that DNAinstability may have an important role to play in the subclonalprogression of human HCC.     

CLINICOPATHOLOGIC FEATURES AND DIAGNOSISOF COMBINED HEPATOCELLULAR ANDCHOLANGIOCARCINOMA

ＣＬＩＮＩＣＯＰＡＴＨＯＬＯＧＩＣＦＥＡＴＵＲＥＳＡＮＤＤＩＡＧＮＯＳＩＳＯＦＣＯＭＢＩＮＥＤＨＥＰＡＴＯＣＥＬＬＵＬＡＲＡＮＤＣＨＯＬＡＮＧＩＯＣＡＲＣＩＮＯＭＡＬｕＪｉａｎｐｉｎｇ路建平；ＣａｉＷｅｉｍｉｎ蔡为民；ＨａｙａｓｈｉＫｅｉｋｉ１林肇辉...     

Prognostic significance of c-myc and AIB1 amplification in hepatocellular carcinoma. A broad survey using high-throughput tissue microarray

BACKGROUND: Amplifications of 1q21, c-myc at 8q24.1, and AIB1 at 20q12 are genetic alterations that are detected frequently in hepatocellular carcinoma (HCC). The authors evaluated the association of these amplifications with the prognosis of patients with HCC. METHODS: In the current study, amplification of 1q21, c-myc, and AIB1 was analyzed in 560 specimens from 400 patients with HCC and 20 patients with benign liver lesions using fluorescence in situ hybridization with high-throughput tissue microarray. Differences of amplification patterns were compared between small and large HCC, single nodular and multiple nodular HCC, primary and metastatic HCC, and primary and recurrent HCC. RESULTS: Significant differences between single nodular and multiple nodular HCC were detected in c-myc amplification (12% vs. 38%; P < 0.01) and AIB1 amplification (16% vs. 30%; P < 0.05). More frequent c-myc amplification was detected in metastatic HCC (45%) compared with primary HCC (29%) and in recurrent HCC (60%) compared with primary HCC (38%). Similarly, more frequent AIB1 amplification was observed in metastatic HCC (41%) compared with primary HCC (23%) and in recurrent HCC (60%) compared with primary HCC (29%). However, no significant differences in 1q21 amplification were observed. CONCLUSIONS: The current results strongly suggest that amplifications of the c-myc and AIB1 oncogenes are late genetic alterations in the progression of HCC and are correlated with a poor prognosis.     

特异性抗肝癌噬菌体单链抗体的应用研究

目的体外观察特异性抗肝癌(HCC)噬菌体单链抗体(ScFv)对HCC细胞生长和凋亡的影响.方法通过构建的特异性抗HCC噬菌体ScFv库在大肠杆菌HB2151中表达,制备游离ScFv,应用细胞培养、DNA凝胶电泳和流式细胞仪(FCM)技术检测抗体对HCC细胞生长和凋亡的影响.结果特异性抗HCC噬菌体ScFv处理的HCC细胞的生长速度明显减慢,克隆形成和附壁能力减弱,细胞存活率降低,DNA凝胶电泳可见典型凋亡梯状带;FCM检测发现抗体处理后HCC细胞凋亡率达32.6%,明显高于对照组(P＜0.01).结论应用噬菌体表面呈现技术和基因克隆技术构建的特异性抗HCC噬菌体ScFv具有抑制HCC细胞生长、促进HCC细胞凋亡的功能.     

Characteristics and prognosis of hepatocellular carcinoma detected in sustained responders to interferon therapy for chronic hepatitis C

Interferon (IFN) therapy allows the eradication of hepatitis C virus (HCV) in some part of patients with chronic hepatitis C which is major cause of hepatocellular carcinoma (HCC). To clarify characteristics and prognoses of HCC detected in these patients (sustained responders to IFN), we compared HCC in sustained responders with HCC detected in patients without a sustained response (non-sustained responders). Characteristics and prognoses were compared in nine cases of HCC detected in sustained responders after IFN therapy and 61 cases of HCC detected in non-sustained responders at one of five our institutions. HCC in sustained responders often were larger (P=0.0051), less differentiated tumor (P=0.0084) than HCC in non-sustained responders when it was detected. No differences were observed in overall survival rate between sustained responders and non-sustained responders, but disease-free survival was higher in cases of HCC in sustained responders (P=0.0494). HCC detected in sustained responders often appear more advanced when detected than HCC in non-sustained responders, but recurrence seems to be less frequent when the initial HCC is treated sufficiently.     

MicroRNA与肝癌诊治：新的机遇和挑战

MicroRNA(miRNA)广泛参与机体各项生理和病理过程,近年来受到广泛关注且研究进展迅速。肝癌尤其是乙型肝炎相关肝癌是我国的重大疾病,miRNA在肝癌发生、发展过程中发挥着重要作用,在肝癌发生、肿瘤进展、预后判断和生物治疗等方面,miRNA均能通过调控其靶基因的表达参与其中。由于大规模平行测序等miRNA组学研究的新技术进展迅速,肝脏与肝癌miRNA组的研究进一步加深了科研工作者对肝癌相关miRNA的理解。在肝脏中富集表达的miRNA在肝癌组织中均出现表达失调,这些表达失调的重要miRNA已被证明是肝癌基因治疗的潜在靶点。此外,肝癌患者血清中存在的游离miRNA被证实是肝癌诊断和个体化治疗的潜在生物标志物。笔者简要阐述肝癌相关miRNA的表达和作用机制及其在临床肝癌诊断和干预中的潜在意义与价值,并对miRNA给肝癌诊治带来新的机遇和挑战作一展望。     

肝细胞癌NY-ESO-1基因/蛋白表达与临床病理特征及肿瘤转移的关系

背景与目的:NY-ESO-1属癌症-睾丸抗原家族,能激发肿瘤患者同时产生细胞免疫和体液免疫,特异杀伤肿瘤细胞,被认为是目前免疫原性最强的肿瘤抗原。本研究旨在探讨NY-ESO-1在肝细胞癌中的表达及其与肝癌临床病理特征的关系。方法:用逆转录聚合酶链反应(RT-PCR)分析62例肝癌和相应癌旁肝组织NY-ESO-1m RNA表达;将145例肝癌石蜡组织制成芯片(132例有效),应用免疫组织化学EliVisionTM两步法观察NY-ESO-1蛋白的表达和分布。结果:NY-ESO-1基因在肝细胞癌中的阳性率是27.4%(17/62),肝癌伴门脉癌栓者达40%(10/25),高于不伴门脉癌栓的18.9%(7/37);NY-ESO-1蛋白主要分布在肝癌细胞胞浆,在肝癌组织芯片中的阳性率为18.9%(25/132),肝癌伴转移病变者为29.6%(16/54),不伴转移病变的阳性率仅11.5%(9/78),二者比较有显著性差异(P<0.05);NY-ESO-1基因和蛋白在H BsAg阳性肝癌标本中阳性率分别为28.3%(15/53)和19.1%(22/115),AFP≥20滋g/L标本的阳性率为29.5%(13/44)和20.7%(19/93),与H BsAg阴性和AFP正常的肝癌比较均无显著性差异(P>0.05);所有癌旁肝组织均未见NY-ESO-1的表达。结论:NY-ESO-特异表达于肝癌细胞,在有转移病变的病例中有较高的阳性率,提示NY-ESO-1可能与肝癌病情进展和转移有关,可作为肝癌,特别是伴有转移病变     

Secular trends and geographic variations of hepatitis B virus and hepatitis C virus-associated hepatocellular carcinoma in Taiwan

Etiological variations in hepatocellular carcinoma (HCC) exist across different geographic areas. To gain better control of HCC, we retrospectively studied the secular trends and geographic variations in hepatitis B virus (HBV)-related and hepatitis C virus (HCV)-related HCCs in Taiwan. A total of 18,423 HCC cases enrolled in 8 medical centers from 1981 to 2001 were reviewed. Overall, 67% of male HCC in Taiwan was related to HBV infection whereas 55.2% of female HCC in Taiwan was related to HCV infection. The mean age of patients with HBV-related HCC was 53.2 +/- 13.6 years, while the mean age of patients with HCV-related HCC was 65.1 +/- 9.1 years (p < 0.001). The male/female ratio was 6.4 for HBV-related HCC, while it was 1.7 for the HCV-related HCC (p < 0.001). The percentage of HBV-related HCC progressively decreased from 81.5 to 66.2% in males, and from 66.7 to 41.4% in females over the study period. Our study demonstrates that the percentage of HBV-related HCC has progressively decreased over the last 20 years. The relative decrease in HBV-related HCC was not due to a decrease in HBV-related HCC death. Instead, it was caused by an increase in HCV-related HCC. Prevention of new HCV infection and the treatment of chronic hepatitis C should be the primary goals, which will result in better control of HCC in the future, even in an HBV-endemic area like Taiwan.     

DNA fragmentation and cell proliferation correlated with tumor grade in patients with hepatocellular carcinoma

BACKGROUND: DNA fragmentation and cell proliferation in patients with hepatocellular carcinoma (HCC) have not been well described on fine-needle aspiration biopsies (FNABs). To investigate the contribution of apoptosis, a major mechanism of cell death, to the growth of HCC, the authors analyzed both apoptosis and cell proliferation in patients with HCC. METHODS: The authors studied 50 tumors from 50 patients with HCC: Ten tumors were well-differentiated HCC, 24 tumors were moderately differentiated HCC, and 16 tumors were poorly differentiated HCC. The detection of DNA fragments in situ using the terminal deoxyribonucleotidyl transferase (TDT)-mediated dUTP-digoxigenin nick-end labeling (TUNEL) assay was applied to investigate active cell death (apoptosis), and the MIB-1 antigen was used to investigate cell proliferation. RESULTS: The TUNEL indices were 0.34 +/- 0.08, 082 +/- 0.30, and 2.0 +/- 0.95 in well-differentiated HCC, moderately differentiated HCC, and poorly differentiated HCC, respectively. The MIB-1 antigen labeling indices were 6.7 +/- 0.10, 13.2 +/- 3.4; and 26.9 +/- 6.5, respectively, in the same order of tumor differentiation. The differences in both TUNEL and MIB-1 labeling indices were significant between well differentiated HCC, moderately differentiated HCC, and poorly differentiated HCC, and a positive correlation was found between the TUNEL indices and the MIB-1 indices. CONCLUSIONS: Apoptosis (cell death) and cell proliferation increase as the grade of differentiation decreases in HCC, suggesting a rapid turnover of tumor cells in tumors with lower grades of differentiation, and apoptosis may play an important role in the growth of tumors in patients with HCC.     

Hepatocellular carcinoma with a central scar and a scalloped tumor margin resembling focal nodular hyperplasia in macroscopic appearance

BACKGROUND: We sometimes encounter hepatocellular carcinoma (HCC) with a central scar and a scalloped tumor margin resembling focal nodular hyperplasia (FNH) in macroscopic appearance. The fibrolamellar variant sometimes shows this appearance; however, this type of HCC can be clearly differentiated from fibrolamellar variants on the basis of clinical and histopathological findings. The clinical features of patients with this type of HCC need to be clarified. METHODS: From 1988 to 1999, 1,043 patients with HCC underwent hepatectomy at our institution. Histopathological examinations show that fibrolamellar HCC was not included in the series. We selected HCC with a central scar and a scalloped tumor margin resembling FNH in macroscopic appearance. We refer to such tumors as scalloped HCC. We compared the clinical findings and surgical outcomes between patients with scalloped HCC and patients with simple nodular HCC. RESULTS: Of the 1,043 cases of HCC, 31 (3%) and 571 (55%) were scalloped HCC and simple nodular HCC, respectively. The mean age of the patients with scalloped HCC was 60.7 years, and that of the patients with simple nodular HCC was 62.6 years, without significant difference. The rates of hepatitis C virus infection and liver cirrhosis and serum alpha-fetoprotein levels were significantly lower, and Child-Pugh class and surgical outcomes were significantly better in patients with scalloped HCC than in those with simple nodular HCC. In multivariate analysis, Child-Pugh class (P < 0.001), tumor size (P = 0.046), and gross appearance (P = 0.009) were independent significant prognostic factors. CONCLUSION: HCC with a central scar and a scalloped tumor margin resembling FNH occurs in non-cirrhotic patients in their 60s and is associated with a good surgical outcome.     

人和大鼠肝细胞癌中骨桥蛋白表达的定量检测

目的骨桥蛋白(Osteopontin,OPN)是一种分泌性的磷酸糖蛋白,参与了包括肝癌在内的多种恶性肿瘤的增殖和转移,本文检测了 OPN基因在人肝细胞癌组织和大鼠肝癌模型中的表达。方法实时荧光定量逆转录PCR检测OPN基因表达,二乙基亚硝胺(diethylnitrosamine,DENA)诱导SD大鼠肝癌模型并动态检测在大鼠肝癌发生发展过程中的OPN基因表达。结果在103例人肝细胞癌病例中69例(67％)肝癌组织中OPN基因表达水平高于癌旁组织,其中58例(56％)超过2倍以上,肝癌和癌旁组织中OPN平均表达水平具有明显差异(0．53±0．91和0．11±0．28,P<0．001)。大鼠肝癌模型中随着肝癌的发生和发展OPN表达水平逐渐上升。结论OPN在肝癌组织中高表达并且随着肝癌的发生发展逐渐升高。     

肝细胞癌HLA—DR抗原的研究及意义

目的：探讨人白细胞DR抗原(HLA-DR)在人原发性肝细胞癌(简称肝癌)的表达情况及其意义。方法：分别采用免疫组化ABC法和流式细胞仪检测了HLA-DR在46例人肝癌组织和4种培养的人肝癌细胞系(SMMC-7721、HCC-9204、BEL-7402和HHCC)的表达情况。结果：39.1％(18／46例)的肝癌组织癌细胞可表达HLA-DR,而在癌旁非肿瘤细胞为阴性。4种肝癌细胞系都基本上不表达HLA-DR。结论：肝癌组织可在一定程度上表达HLA-DR,但是培养的肝癌细胞系基本上不表达。HLA—DR与肝癌发生、发展的关系及其在抗肝癌免疫应答中的作用有待进一步研究。     

Prognostic value of periodic Acid-schiff (pas) staining of fine-needle aspirates from patients with primary hepatocellular-carcinoma

The relationships of cytological findings on periodic acid-Schiff (PAS) staining of fine-needle aspirates of hepatocellular carcinomas (HCC) with the length of survival of patients, their therapeutic response after transcatheter arterial embolization (TAE), and the tumor volume doubling time (TVDT) before chemoembolization were investigated in 74 patients with primary HCC. On the basis of cytologic findings on PAS-staining, HCC was classified into PAS-positive, mixed, and PAS-negative types. The two-year survival (70%) of patients with PAS-positive HCC was significantly longer than those of patients with the mixed or PAS-negative type of HCC. The TVDT of PAS-positive HCC was also significantly longer than that of the mixed type of HCC. These findings indicate that cytological findings on PAS-staining of HCC are useful in assessing the prognosis of patients with HCC.     

Bright loop appearance; a characteristic ultrasonography sign of early hepatocellular carcinoma

Ultrasonography (US) and computed tomography (CT) are the most effective screening methodologies for hepatocellular carcinoma (HCC). In our US screening, 20% of small HCC nodules less than 20 mm in diameter were detected as hyperechoic tumors. Among these hyperechoic HCC nodules, we have often observed (BL) which is defined as hypoechoic nodules in the hyperechoic tumor. In this study, we report that the BL is a sign of dedifferentiation of early stage of HCC with fatty change by US. From 1994 to 1998, we performed tumor targeting needle biopsy in 938 hepatic nodular lesions. Among them, 284 nodules <20 mm in diameter, histologically diagnosed as HCC, were studied. BL is defined as a hyperechoic tumor containing a hypoechoic nodule >4 mm in diameter by US. Among 284 nodules, well, moderately and poorly differentiated HCC were 183 (64.4%), 100 (35.2%) and 1 (0.4%), respectively. On US, hypoechoic, isoechoic, and hyperechoic nodules were 188 (66.2%), 32 (11.3%) and 64 (22.5%), respectively. Forty-seven nodules of 64 hyperechoic HCC nodules <20 mm in diameter, 47 nodules (73.4%) showed fatty changes. Of 64 hyperechoic HCC nodules, we recognized 22 nodules (34.4%) as BL. The proportion of BL type hyperechoic nodules increased with the tumor size. Two hyperechoic nodules followed by US changed to BL with tumor enlargement. Histologic examination of a resected HCC with BL showed that hyperechoic HCC nodule represented well-differentiated HCC with fatty change and inner hypoechoic lesion represented moderately differentiated HCC without fatty change. In US screening for HCC, BL was often observed in HCC nodules from 11 to 20 mm in diameter. Histologic examination revealed that BL of HCC on US was associated with tumor progression and indicated dedifferentiation showing moderately differentiated HCC in well-differentiated HCC with fatty change.     

Clinicopathologic features of poorly differentiated hepatocellular carcinoma

BACKGROUND AND OBJECTIVES: Clinicopathologic features of poorly differentiated hepatocellular carcinoma (HCC) have not been elucidated. The purpose of this study was to clarify the characteristics of poorly differentiated HCC in hepatectomized patients. METHODS: From 1986 to 2001, 354 HCC patients underwent curative hepatectomy in our institution and were prospectively followed. Histological examinations revealed 43 well-differentiated HCC tumors, 273 moderately differentiated HCC tumors, and 38 poorly differentiated HCC tumors. Clinicopathologic factors and outcomes after hepatectomy were compared statistically. RESULTS: Only serum alpha-fetoprotein level was significantly different in the poorly differentiated HCC group from that in the moderately differentiated HCC group preoperatively (P=0.0001). Although there were no significant differences between overall survival rates or between disease-free survival rates in the three groups, distant metastasis within 2 years after hepatectomy occurred more frequently in the poorly differentiated HCC group (21%) than in the well-differentiated HCC group (2%) (P=0.011) or moderately differentiated HCC group (8%) (P=0.018). Distant metastasis occurred in about 40% of patients in the poorly differentiated HCC group with tumor size greater than 3 cm. CONCLUSIONS: Poorly differentiated HCC tumors larger than 3 cm are already of advanced stage representing distant metastasis in the early period after hepatectomy.     

Fatty liver creates a pro‐metastatic microenvironment for hepatocellular carcinoma through activation of hepatic stellate cells

Fatty liver (FL) is associated with development of hepatocellular carcinoma (HCC). However, whether FL itself promotes the progression of HCC is unclear. We recently found that hepatic stellate cells (HSCs) were prominently activated in the steatotic liver. Here, we investigated whether steatotic livers promote HCC progression and whether HSCs of steatotic liver are associated with HCC progression. We implanted rat HCC cells into diet‐induced steatotic livers in rats via portal vein injection. Thereafter, HSCs and HCC cells were co‐implanted subcutaneously into nude rats. Migration and proliferation of HCC cells were measured, and activation of ERK and Akt in these cells was determined by western blotting. Chemokines secreted from HSCs and HCC cells were also evaluated by ELISA. Steatotic livers significantly promoted HCC metastasis compared with non‐steatotic livers. Additionally, co‐implantation of HCC cells with HSCs from steatotic livers produced significantly larger tumors in recipient rats as compared to those induced by HCC cells co‐implanted with HSCs from normal livers (NLs). HSCs isolated from steatotic livers, compared with HSCs isolated from NLs, secreted greater amounts of interleukin‐1α, vascular endothelial growth factor, and transforming growth factor‐β. These cytokines may enhance the proliferation and migration of HCC cells by increasing the phosphorylation of ERK and Akt in HCC cells. Moreover, we noted that the Rho‐kinase inhibitor deactivated activated HSCs and attenuated HCC progression. In conclusion, the rat steatotic liver microenvironment favors HCC metastasis, and this effect appears to be promoted by activated HSCs in the steatotic liver.     

Cyr61和VEGF在肝细胞癌及癌周肝硬化组织中的表达及相关性分析

目的分析高半胱氨酸蛋白16（Cyr61）和血管内皮生长因子（VEGF）在肝细胞癌、癌周肝硬化组织中的表达及相关性,探讨其在肝癌发生过程中的作用。方法采用免疫组化S-P法检测58例原发性肝细胞肝癌（HCC）及癌周肝硬化组织中Cyr61和VEGF蛋白的表达,并与其临床病理特征比较分析。结果Cyr61、VEGF在癌周肝硬化组织中的表达均高于HCC,差异有统计学意义（P〈0.01）;Cyr61、VEGF蛋白的表达均与肿瘤的转移密切相关（P〈0.05）;相关性检验提示Cyr61、VEGF在HCC组织、癌周肝硬化组织中呈正相关（r=0.444,P〈0.01）。结论Cyr61、VEGF异常表达与肝硬化肝癌的发展密切相关,可能在肝硬化向肝癌转化和肿瘤血管生成过程中发挥重要的作用,为肝癌的早期诊断提供了较为客观的参考指标。     

High prevalence of hepatitis C virus infection in schistosomiasis japonica patients associated with hepatocellular carcinoma

Schistosomiasis japonica (SCJ) patients frequently develop hepatocellular carcinoma (HCC). This study investigated relationship between SCJ infection, hepatitis virus infection, and incidence of HCC, in 25 patients with chronic SCJ infection and HCC (SCJ with HCC group), 51 patients with chronic SCJ infection without HCC (SCJ group) and 65 HCC patients without SCJ (HCC group). Number of patients who were positive to HBsAg or hepatitis B virus DNA were 4 (16.0%) in the SCJ with HCC group, none (0%) in the SCJ group, and 5 (7.9%) in the HCC group; while number of patients who were positive to anti-hepatitis C virus antibody were 21 (87.5%) in the SCJ with HCC group, 3 (5.9%) in the SCJ group, and 58 (84.6%) in the HCC group. Biopsy was performed for all patients, and background histological features of each specimen were evaluated based on the histological activity index scoring system. Mean scores of inflammatory changes in both the portal area and parenchyma in the SCJ with HCC group were significantly higher than those in the SCJ group. Nodular formation which is common in post-viral hepatitis was frequently observed in the SCJ with HCC group, and histological changes in non-cancerous area of the SCJ with HCC group showed the characteristics of chronic viral hepatitis. We conclude that infection of hepatitis virus, particularly hepatitis C virus, affects synergistically on the hepatocarcinogenesis in patients having SCJ infection.     

肝癌组织中EGFL9基因的表达及其对Huh-7肝癌细胞系增殖、侵袭和迁移的影响

目的:研究表皮生长因子样结构域9（epiderma growth factor-like domain 9,EGFL9）基因在肝癌组织及细胞系中的表达水平及其对Huh-7肝癌细胞系增殖、侵袭和迁移的影响。方法:采用实时荧光定量PCR（quantitative real-time PCR,RT-qPCR）方法检测EGFL9基因在20例肝癌及对应的癌旁肝组织标本中的表达水平。下载癌症基因组图谱（The Cancer Genome Atlas,TCGA）数据库内肝癌基因表达数据,对EGFL9在肝癌中的表达进行分析。RT-qPCR检测EGFL9基因在Huh-7、SMMC-7721及HepG2三种常见的肝癌细胞系和HL-7702正常肝脏细胞系中的表达水平。采用慢病毒介导的siRNA及基因转导技术分别构建EGFL9基因敲减及过表达的Huh-7肝癌细胞,以噻唑蓝（methyl thiazolyl tetrazolium,MTT）法、Transwell侵袭实验和迁移实验观察EGFL9基因敲减及过表达对Huh-7肝癌细胞增殖、侵袭和迁移的影响。结果:RT-qPCR结果显示,EGFL9基因在20例肝癌组织中的表达量高于对应的癌旁组织。TCGA数据库分析结果也显示,EGFL9在肝癌组织中的平均表达量明显高于癌旁组织。EGFL9在3株肝癌细胞系中的表达水平均高于正常肝脏细胞系。EGFL9基因敲减的Huh-7肝癌细胞的增殖速度明显慢于对照Huh-7肝癌细胞,其侵袭、迁移能力也明显被抑制;EGFL9基因过表达的Huh-7肝癌细胞实验结果则与之相反。结论:EGFL9在肝癌组织和细胞中的表达水平明显上调,且可促进肝癌细胞的增殖、侵袭及迁移能力,提示EGFL9可能是一个潜在的肝癌治疗靶点。