Ranjpour Maryam, Wajid Saima, Jain Swatantra Kumar
Department of Biotechnology, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi, India.
Department of Medical Biochemistry, HIMSR, Jamia Hamdard, New Delhi, India. Electronic Address:
Cell J. 2020 Apr;22(1):17-22. doi: 10.22074/cellj.2020.6527. Epub 2019 Sep 8.
Liver cancer is the third rank amongst the common malignancies, causing maximum death in the patients diagnosed with cancers. Currently available biomarkers are not enough sensitive for early diagnosis of hepatocellular carcinoma (HCC). This makes difficult management of HCC. With the aim of finding new generation of proteomic-based biomarkers, the represented study was designed to characterize the differentially expressed proteins at different stages of HCC initiation and at progression. This could lead to find potential biomarkers for early detection of HCC.
In this experimental study, we report induction of HCC by administrating chemical carcinogens in male Wistar rats. Disease progression was monitored by histological evaluation. Serum proteomic analyses such as 2 dimensional (2D)-electrophoresis, MALDI-TOF-MS/MS and Western blot have been used to analyze and characterize the differentially expressed proteins during HCC development.
HCC initiation and tumorigenesis were observed at one and four months post carcinogen treatment, respectively. One of the differentially-expressed proteins, namely, cytosolic phospholipase A2 delta was significantly up-regulated at very early stage of HCC development. Its expression continued to increase during cancer progression and hepatotumorigenesis stages. Its elevated expression has been confirmed by Western blot analysis. Consistent to this, analyses of the sera in the clinically confirmed liver cancer patients showed elevated expression of this protein, further validating our experimental results.
This study suggests that elevation in the expression of cytosolic phospholipase A2 delta is associated with progression of HCC.
肝癌是常见恶性肿瘤中的第三大死因，在癌症确诊患者中致死率最高。目前可用的生物标志物对肝细胞癌（HCC）的早期诊断不够敏感，这使得HCC的治疗颇具难度。为了寻找新一代基于蛋白质组学的生物标志物，本研究旨在对HCC起始和进展不同阶段差异表达的蛋白质进行表征，以期找到HCC早期检测的潜在生物标志物。
在本实验研究中，我们报告了通过给雄性Wistar大鼠施用化学致癌物诱导HCC的过程。通过组织学评估监测疾病进展。血清蛋白质组分析，如二维（2D）电泳、基质辅助激光解吸电离飞行时间串联质谱（MALDI-TOF-MS/MS）和蛋白质免疫印迹法，已用于分析和表征HCC发展过程中差异表达的蛋白质。
分别在致癌物处理后1个月及4个月观察到HCC起始和肿瘤发生。其中一种差异表达蛋白，即胞质磷脂酶A2δ，在HCC发展的极早期显著上调。其表达在癌症进展和肝肿瘤发生阶段持续增加。蛋白质免疫印迹分析证实了其表达升高。与此一致的是，对临床确诊肝癌患者血清的分析显示该蛋白表达升高，进一步验证了我们的实验结果。
本研究表明，胞质磷脂酶A2δ表达升高与HCC进展相关。
