Wang Lina, Ding Qin, Zhao Li, Pan Yu, Song Zhengxia, Qin Yanan, Yan Xuebing
Department of Infectious Disease, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China.
Department of Respiratory, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China.
Oncol Lett. 2018 Aug;16(2):2113-2118. doi: 10.3892/ol.2018.8918. Epub 2018 Jun 6.
The aim of the present study was to investigate the expression of bone morphogenetic protein-7 (BMP-7), gremlin, and p-Smad/1/5/8 in carcinomatous and para-carcinoma tissue specimens from patients with hepatocellular carcinoma (HCC). The association of serum BMP-7 levels with clinicopathological parameters was examined to assess its relevance as a clinical biomarker for HCC. A total of 27 patients with HCC and 7 healthy subjects were included. Gene expression levels of BMP-7 and p-Smad1/5/8 were examined by reverse transcription-quantitative polymerase chain reaction. Immunohistochemical and western blot analysis were performed to determine the protein expression of target genes. The serum levels of BMP-7 were assessed by enzyme linked immunosorbent assay. The mRNA and protein expression of BMP-7 and gremlin were significantly down- and upregulated in HCC tumor tissues, respectively, compared with para-carcinoma tissues (P<0.05). The association of BMP-7 and gremlin expression with the differentiation status of HCC was also analyzed. There was a relatively higher level of BMP-7 and a lower level of gremlin expression in tumor tissues from patients with highly differentiated HCC when compared with poorly or moderately differentiated HCC (BMP-7, F=42.29, P<0.01; gremlin, F=37.93, P<0.01). Furthermore, the level of BMP-7 and p-Smad1/5/8 was decreased in patients with advanced stages of HCC, when compared with stage I HCC. The findings from the present study suggest that the BMP-7/p-Smad signaling pathway may be involved in the pathogenesis of HCC. The serum levels of BMP-7 may serve as a potential biomarker for HCC.
本研究旨在调查骨形态发生蛋白7（BMP-7）、gremlin以及p-Smad/1/5/8在肝细胞癌（HCC）患者癌组织和癌旁组织标本中的表达情况。检测血清BMP-7水平与临床病理参数的相关性，以评估其作为HCC临床生物标志物的相关性。共纳入27例HCC患者和7名健康受试者。通过逆转录定量聚合酶链反应检测BMP-7和p-Smad1/5/8的基因表达水平。进行免疫组织化学和蛋白质印迹分析以确定靶基因的蛋白表达。采用酶联免疫吸附测定法评估血清BMP-7水平。与癌旁组织相比，HCC肿瘤组织中BMP-7和gremlin的mRNA及蛋白表达分别显著下调和上调（P<0.05）。还分析了BMP-7和gremlin表达与HCC分化状态的相关性。与低分化或中分化HCC患者相比，高分化HCC患者肿瘤组织中BMP-7水平相对较高，gremlin表达水平较低（BMP-7，F=42.29，P<0.01；gremlin，F=37.93，P<0.01）。此外，与I期HCC患者相比，晚期HCC患者的BMP-7和p-Smad1/5/8水平降低。本研究结果表明，BMP-7/p-Smad信号通路可能参与HCC的发病机制。血清BMP-7水平可能作为HCC的潜在生物标志物。
