肝细胞肝癌(HCC)中PDGF-A的表达及其临床意义  

The expression of PDGF-A in hepatocellular carcinoma (HCC) and its clinical significance

作　　者：高琼媚 刘丹阳 周仲文 张乔安 刘国元 曾文姣 GAO Qiong-mei;LIU Dan-yang;ZHOU Zhong-wen;ZHANG Qiao-an;LIU Guo-yuan;ZENG Wen-jiao(Department of Pathology,School of Basic Medical Sciences,Fudan University,Shanghai 200032,China;Department of Pathology,Obstetrics and Gynecology Hospital,Fudan University,Shanghai 200011,China;Department of Pathology,Huashan Hospital,Fudan University,Shanghai 200040,China;Department of Dermatology,Huashan Hospital,Fudan University,Shanghai 200040,China)

机构地区：[1]复旦大学基础医学院病理学系,上海200032 [2]复旦大学附属妇产科医院病理科,上海200011 [3]复旦大学附属华山医院病理科,上海200040 [4]复旦大学附属华山医院皮肤科,上海200040

出　　处：《复旦学报（医学版）》2019年第3期302-308,323,共8页Fudan University Journal of Medical Sciences

基　　金：国家自然科学基金青年项目(81001062);上海市自然科学基金(15ZR1403800)~~

摘　　要：目的阐明血小板源性生长因子A(platelet-derived growth factor A,PDGF-A)在人肝细胞肝癌(hepatocellular carcinoma,HCC)组织中的表达情况及临床意义。方法在手术切除的50例HCC组织中,应用定量RT-PCR的方法检测PDGF-A mRNA水平,并分析其与临床病理分期之间的关系。采用Western blot检测正常肝细胞株L02和7株肝癌细胞株中PDGF-A蛋白质水平。运用免疫组化方法在43例HCC石蜡组织中检测PDGF-A蛋白质水平。再利用免疫荧光双染色方法检测HCC组织中间质区域炎症细胞中PDGF-A与炎症细胞标志物(CD4、CD8、CD19和CD68)共表达情况。结果与相应癌旁肝组织相比,HCC癌组织PDGF-A mRNA水平升高,约50%(24/50例)癌组织PDGF-A mRNA水平是癌旁肝组织的2倍及以上,这种差异在BCLC 0期和C期的HCC病例中更为显著。PDGF-A蛋白质见于L02、SMMC-7721、HCCLM3和MHCC97-H细胞株,而HepG2、Hep3B、Huh7和BEL-7402细胞株未检测到该蛋白质。近60%的HCC病例中,肝癌细胞表达PDGF-A,阳性染色有两种分布方式:弥漫于胞质内及在细胞质/细胞膜局部聚集。PDGF-A也大量分布于肿瘤间质区域和紧邻癌组织间质区域的炎症细胞(CD4^+、CD8^+、CD19^+和CD68^+)中。结论HCC癌组织PDGF-A基因表达高于癌旁肝组织,在早期和进展期(BCLC 0和C期)病例更为明显;PDGF-A蛋白表达于HCC癌细胞和间质炎症细胞。Objective To elucidate the expression and significance of platelet-derived growth factor A (PDGF-A) in human hepatocellular carcinoma (HCC) tissues. Methods Quantitative RT-PCR was used to detect the mRNA level of PDGF-A in tissues resected from 50 patients with HCC,and the relationship between PDGF-A with clinical pathological stage was analyzed.Western Blot was used to detect the protein level of PDGF-A in L02 liver cell line and 7 hepatoma cell lines.Immunohistochemistry was used to detect the distribution of PDGF-A protein in 43 HCC paraffin tissues.The co-expression of PDGF-A and the molecular makers (CD4,CD8,CD19 and CD68) in inflammatory cells were observed by using double immunofluorescence staining technology. Results Compared with the corresponding adjacent non-tumorous livers,the mRNA level of PDGF-A in HCC tumor tissues was increased,and about 50%(24 of 50 cases) of HCC tumor tissues had over 2 times PDGF-A mRNA level of their adjacent liver tissues.This difference was more significant in the very early stage and advanced stage of HCC (BCLC stage 0 and C).PDGF-A protein was detected in L02,SMMC-7721,HCCLM3 and MHCC97-H cell lines,but not in HepG2,Hep3B,Huh7 and BEL-7402 cell lines.In nearly 60% cases,HCC tumor cells expressed PDGF-A protein,and positive staining had two distribution patterns:diffuse in cytoplasm and local aggregation in cytoplasm/cell membrane.PDGF-A was also abundantly expressed in inflammatory cells (CD4^+,CD8^+,CD19^+ and CD68^+) in tumorous and tightly adjacent interstitium. Conclusions The mRNA level of PDGF-A in HCC tumor tissues was higher than that in adjacent tissues,especially in very early and advanced stages.In HCC tissue,PDGF-A protein was expressed in tumor cells and interstitial inflammatory cells.

关 键 词：血小板源性生长因子A(PDGF-A) 肝细胞肝癌(HCC) 肝癌细胞株 炎症细胞 

分 类 号：R735.7[医药卫生—肿瘤]