肝肿瘤%癌,肝细胞%肝细胞生长因子%逆转录聚合酶链反应%酶联免疫吸附测定
肝腫瘤%癌,肝細胞%肝細胞生長因子%逆轉錄聚閤酶鏈反應%酶聯免疫吸附測定
간종류%암,간세포%간세포생장인자%역전록취합매련반응%매련면역흡부측정
Liver neoplasms%Carcinoma,hepatocellular%Hepatocyte growth factor%Reverse transcription-quantitative polymerase chain%Enzyme-linked immunosorbent assay
目的 探讨肝细胞生长因子(HGF)在慢性肝炎、肝硬化、肝细胞癌(HCC)患者肝组织和血清中的表达水平及其临床意义.方法 收集2003年12月至2008年8月期间天津市第三中心医院11份正常、6份肝炎、20份肝硬化、60份HCC组织(高分化21份、中分化23份、低分化16份),及其癌旁0、1、2、3 cm组织(N0、N1、N2、N3)各24、21、54和43份.用实时荧光定量逆转录(RT)-PCR分析不同肝组织HGF mRNA表达；同时,用ELISA测定健康体检者、肝炎、肝硬化患者血清标本各20份及HCC患者57份术前1d、术后1周内血清标本的HGF浓度.多组间组织HGF mRNA水平比较用Kruskal-Wallis检验,两组间组织HGF mRNA水平比较用Mann-Whitney U检验.多组间血清HGF浓度比较用单因素方差分析,两组间血清HGF浓度比较用LSD-t检验.性别、年龄、肿瘤类型、肿瘤直径等临床因素对HCC患者组织、血清HGF水平的影响及其与患者预后的相关分析分别用Logistic回归分析及Cox比例风险模型.筛选出影响患者术后生存的独立预后指标,以中位数水平分层,由Kaplan-Meier生存曲线计算不同分层水平的死亡终点事件发生风险,并用Log-rank检验评价分层间死亡终点事件发生率.结果 实时荧光定量RT-PCR检测健康对照组、肝炎、肝硬化、N3、N2、N1、N0、HCC组HGF mRNA表达分别为0.99(0.78～1.66)、2.15 (1.06～3.40)、1.78(1.18～2.73)、4.59(2.67 ～8.63)、3.86(2.25 ～6.45)、3.12(1.59 ～5.74)、2.92(0.88 ～5.99)、0.48(0.19～1.06);ELISA检测血清HGF在健康体检者、肝炎、肝硬化及HCC患者术前1d、术后1周的浓度分别为(0.31±0.05)、(0.65±0.07)、(1.27 ±0.30)、(2.06±0.66)及(2.14±0.52)μg/L.不同肝组织相比,HGF mRNA在N3组织中表达最高,而在HCC组织中的表达不仅低于以上各良性肝病组织,而且低于正常肝组织(U=196.50,P=0.03)；不同血清HGF浓度相比,HGF在肝炎、肝硬化、HCC患者血清中的浓度均明显高于健康对照组,且HCC患者术后1周的血清HGF浓度高于其术前血清HGF浓度(t=2.70,P＜0.01)；Logistic回归分析显示,HCC患者癌组织及血清HGF水平分别受肿瘤数目及Child-pugh肝功能分级影响,OR分别为0.15(95％ CI:0.03 ～0.72,P＜0.05)和0.13(95％口:0.27 ～0.89,P＜0.05).Cox比例风险模型分析显示,肿瘤组织HGF mRNA水平、血清HGF浓度是影响HCC患者术后生存的独立预后指标,OR分别为0.02(95％ CI:0.00 ～0.52,P＜0.05)和10.01(95％CI:1.16 ～86.23,P＜0.05).以肿瘤组织HGF mRNA 2-AACT中位数0.49对HCC患者进行分层分析显示,两组患者术后累计生存率差异无统计学意义(x2=0.13,P=0.72).以血清浓度中位数0.69 μg/L对HCC患者进行分层分析,HGF≥0.69 μg/L的HCC患者,其术后死亡的风险是HGF＜0.69 μg/L患者的2.84倍(95％ CI:1.03 ～7.92,P＜0.05).结论 HCC患者癌组织中HGF mRNA表达降低,但癌旁组织HGF mRNA表达和血清HGF浓度明显升高,且血清HGF浓度影响患者预后,检测血清HGF有望用于评估HCC患者预后.
目的 探討肝細胞生長因子(HGF)在慢性肝炎、肝硬化、肝細胞癌(HCC)患者肝組織和血清中的錶達水平及其臨床意義.方法 收集2003年12月至2008年8月期間天津市第三中心醫院11份正常、6份肝炎、20份肝硬化、60份HCC組織(高分化21份、中分化23份、低分化16份),及其癌徬0、1、2、3 cm組織(N0、N1、N2、N3)各24、21、54和43份.用實時熒光定量逆轉錄(RT)-PCR分析不同肝組織HGF mRNA錶達；同時,用ELISA測定健康體檢者、肝炎、肝硬化患者血清標本各20份及HCC患者57份術前1d、術後1週內血清標本的HGF濃度.多組間組織HGF mRNA水平比較用Kruskal-Wallis檢驗,兩組間組織HGF mRNA水平比較用Mann-Whitney U檢驗.多組間血清HGF濃度比較用單因素方差分析,兩組間血清HGF濃度比較用LSD-t檢驗.性彆、年齡、腫瘤類型、腫瘤直徑等臨床因素對HCC患者組織、血清HGF水平的影響及其與患者預後的相關分析分彆用Logistic迴歸分析及Cox比例風險模型.篩選齣影響患者術後生存的獨立預後指標,以中位數水平分層,由Kaplan-Meier生存麯線計算不同分層水平的死亡終點事件髮生風險,併用Log-rank檢驗評價分層間死亡終點事件髮生率.結果 實時熒光定量RT-PCR檢測健康對照組、肝炎、肝硬化、N3、N2、N1、N0、HCC組HGF mRNA錶達分彆為0.99(0.78～1.66)、2.15 (1.06～3.40)、1.78(1.18～2.73)、4.59(2.67 ～8.63)、3.86(2.25 ～6.45)、3.12(1.59 ～5.74)、2.92(0.88 ～5.99)、0.48(0.19～1.06);ELISA檢測血清HGF在健康體檢者、肝炎、肝硬化及HCC患者術前1d、術後1週的濃度分彆為(0.31±0.05)、(0.65±0.07)、(1.27 ±0.30)、(2.06±0.66)及(2.14±0.52)μg/L.不同肝組織相比,HGF mRNA在N3組織中錶達最高,而在HCC組織中的錶達不僅低于以上各良性肝病組織,而且低于正常肝組織(U=196.50,P=0.03)；不同血清HGF濃度相比,HGF在肝炎、肝硬化、HCC患者血清中的濃度均明顯高于健康對照組,且HCC患者術後1週的血清HGF濃度高于其術前血清HGF濃度(t=2.70,P＜0.01)；Logistic迴歸分析顯示,HCC患者癌組織及血清HGF水平分彆受腫瘤數目及Child-pugh肝功能分級影響,OR分彆為0.15(95％ CI:0.03 ～0.72,P＜0.05)和0.13(95％口:0.27 ～0.89,P＜0.05).Cox比例風險模型分析顯示,腫瘤組織HGF mRNA水平、血清HGF濃度是影響HCC患者術後生存的獨立預後指標,OR分彆為0.02(95％ CI:0.00 ～0.52,P＜0.05)和10.01(95％CI:1.16 ～86.23,P＜0.05).以腫瘤組織HGF mRNA 2-AACT中位數0.49對HCC患者進行分層分析顯示,兩組患者術後纍計生存率差異無統計學意義(x2=0.13,P=0.72).以血清濃度中位數0.69 μg/L對HCC患者進行分層分析,HGF≥0.69 μg/L的HCC患者,其術後死亡的風險是HGF＜0.69 μg/L患者的2.84倍(95％ CI:1.03 ～7.92,P＜0.05).結論 HCC患者癌組織中HGF mRNA錶達降低,但癌徬組織HGF mRNA錶達和血清HGF濃度明顯升高,且血清HGF濃度影響患者預後,檢測血清HGF有望用于評估HCC患者預後.
목적 탐토간세포생장인자(HGF)재만성간염、간경화、간세포암(HCC)환자간조직화혈청중적표체수평급기림상의의.방법 수집2003년12월지2008년8월기간천진시제삼중심의원11빈정상、6빈간염、20빈간경화、60빈HCC조직(고분화21빈、중분화23빈、저분화16빈),급기암방0、1、2、3 cm조직(N0、N1、N2、N3)각24、21、54화43빈.용실시형광정량역전록(RT)-PCR분석불동간조직HGF mRNA표체；동시,용ELISA측정건강체검자、간염、간경화환자혈청표본각20빈급HCC환자57빈술전1d、술후1주내혈청표본적HGF농도.다조간조직HGF mRNA수평비교용Kruskal-Wallis검험,량조간조직HGF mRNA수평비교용Mann-Whitney U검험.다조간혈청HGF농도비교용단인소방차분석,량조간혈청HGF농도비교용LSD-t검험.성별、년령、종류류형、종류직경등림상인소대HCC환자조직、혈청HGF수평적영향급기여환자예후적상관분석분별용Logistic회귀분석급Cox비례풍험모형.사선출영향환자술후생존적독립예후지표,이중위수수평분층,유Kaplan-Meier생존곡선계산불동분층수평적사망종점사건발생풍험,병용Log-rank검험평개분층간사망종점사건발생솔.결과 실시형광정량RT-PCR검측건강대조조、간염、간경화、N3、N2、N1、N0、HCC조HGF mRNA표체분별위0.99(0.78～1.66)、2.15 (1.06～3.40)、1.78(1.18～2.73)、4.59(2.67 ～8.63)、3.86(2.25 ～6.45)、3.12(1.59 ～5.74)、2.92(0.88 ～5.99)、0.48(0.19～1.06);ELISA검측혈청HGF재건강체검자、간염、간경화급HCC환자술전1d、술후1주적농도분별위(0.31±0.05)、(0.65±0.07)、(1.27 ±0.30)、(2.06±0.66)급(2.14±0.52)μg/L.불동간조직상비,HGF mRNA재N3조직중표체최고,이재HCC조직중적표체불부저우이상각량성간병조직,이차저우정상간조직(U=196.50,P=0.03)；불동혈청HGF농도상비,HGF재간염、간경화、HCC환자혈청중적농도균명현고우건강대조조,차HCC환자술후1주적혈청HGF농도고우기술전혈청HGF농도(t=2.70,P＜0.01)；Logistic회귀분석현시,HCC환자암조직급혈청HGF수평분별수종류수목급Child-pugh간공능분급영향,OR분별위0.15(95％ CI:0.03 ～0.72,P＜0.05)화0.13(95％구:0.27 ～0.89,P＜0.05).Cox비례풍험모형분석현시,종류조직HGF mRNA수평、혈청HGF농도시영향HCC환자술후생존적독립예후지표,OR분별위0.02(95％ CI:0.00 ～0.52,P＜0.05)화10.01(95％CI:1.16 ～86.23,P＜0.05).이종류조직HGF mRNA 2-AACT중위수0.49대HCC환자진행분층분석현시,량조환자술후루계생존솔차이무통계학의의(x2=0.13,P=0.72).이혈청농도중위수0.69 μg/L대HCC환자진행분층분석,HGF≥0.69 μg/L적HCC환자,기술후사망적풍험시HGF＜0.69 μg/L환자적2.84배(95％ CI:1.03 ～7.92,P＜0.05).결론 HCC환자암조직중HGF mRNA표체강저,단암방조직HGF mRNA표체화혈청HGF농도명현승고,차혈청HGF농도영향환자예후,검측혈청HGF유망용우평고HCC환자예후.
Objective To investigate hepatocyte growth factor (HGF) levels in the tissue and serum of patients with chronic hepatitis,cirrhosis or hepatocellular carcinoma (HCC),and analyze the clinical significances of HGF for HCC.Method Surgical specimens from 97 patients were collected during Dec.2003 to Aug.2008 in the Third Central Hospital.The patients were prospectively enrolled and categorized into four groups:normal subjects ( n =11 ),chronic hepatitis B or C ( n =6＝,cirrhosis ( n =20)and HCC ( n =60 ) including well-differentiated ( n =21 ),moderately differentiated ( n =23 ),poorly differentiated (n =16) specimens.N0 (n =24),N1 (n =21 ),N2 (n =54) and N3 (n =43) were tissues respectively removed from liver at 0,1,2 or 3 cm beyond the margin of tumor.HGF mRNA expression in liver tissues was determined by real-time quantitative reverse transcription- (RT)-PCR.Serum HGF levels in the other cases of normal subjects ( n =20),chronic hepatitis B or C ( n =20),cirrhosis ( n =20) and HCC (n =57) were measured by ELISA.The Kaplan-Meier method with log-rank test was employed for survival analysis.Univariate and multivariate analyses were performed to identify prognostic factors in each group.Results The HGF mRNA in normal subjects,chronic hepatitis,cirrhosis,N3,N2,N1,N0 and HCC were0.99(0.78-1.66),2.15(1.06-3.40),1.78(1.18-2.73),4.59(2.67 -8.63),3.86 ( 2.25 - 6.45 ),3.12 ( 1.59 - 5.74 ),2.92 ( 0.88 - 5.99 ) and 0.48 ( 0.19 - 1.06 ) respectively.The serum concentration of HGF in the normal subjects,chronic hepatitis,cirrhosis and HCC patients were (0.31 ± 0.05 ),(0.65 ± 0.07 ),( 1.27 ± 0.30 ) and ( 2.06 ± 0.66) μg/L respectively.The highest level of HGF mRNA was found in N3,while the HGF mRNA expression in HCC was [ (2.14 ± 0.52 ) μg/L] lower than that not only in the non-tumor tissues,but also in the normal control ( U =196.50,P =0.03 ).The serum concentration of HGF was significantly higher in patients with chronic hepatitis,cirrhosis or HCC than in normal subjects.The serum HGF level of HCC was bounced after hepatectomy (t =2.70,P ＜0.01 ).On the logistic regression analysis,the tumor numbers and Child-pugh were related with the levels of the tissue HGF mRNA and serum HGF of HCC,OR were0.15 (95％CI:0.03-0.72,P＜0.05) and0.13 (95％CI:0.27 -0.89,P ＜0.05 ),respectively.Univariate analysis using the Cox proportional hazards model in the complication groups revealed that the levels of the tissue HGF mRNA and serum HGF were significant risk factors of death for HCC,OR were 0.02 (95％ CI:0.00 - 0.52,P ＜ 0.05 ) and 10.01 (95％ CI:1.16 -86.23,P ＜ 0.05 ),respectively.On the Log-rank analysis,no statistically difference in the cumulative survival was found between the two groups categorized by median (0.49) of tissue HGF mRNA 2 - AACT (X2 =0.13,P =0.72).While the HCC patients were dichotomized by their the median(0.69 μg/L) of serum HGF concentration,the death risk for the patients with higher levels of HGF was increased 2.84 fold than those with lower levels (95％ CI:1.03 - 7.92,P ＜ 0.05 ).Conclusion HGF mRNA expression is decreased in tumor tissues,while its level in tumor adjacent live and serum is significantly elevated and is in association with shortened postoperative survival of HCC patients.
