Dai Liping, Peng Xuan-Xian, Tan Eng M, Zhang Jian-Ying
Department of Biological Sciences & NIH-Sponsored Border Biomedical Research Center, The University of Texas at El Paso, El Paso, TX 79968, USA.
School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, China.
Oncotarget. 2016 Mar 29;7(13):16985-95. doi: 10.18632/oncotarget.7707.
CAPERα, a tumor-associated antigen, was identified from a cDNA clone with autoantibody from a patient with hepatocellular carcinoma (HCC). It has been implicated, by way of alternative splicing of VEGF pre-mRNA, in the regulation of microvessel formation in Ewing's sarcoma. In this study, we looked for possible association of alterations in CAPERα with microvessel density in HCC.
Enzyme-linked immunosorbent assay using recombinant CAPERα as antigen were used to detect antibody against CAPERα. Immunohistochemistry (IHC) on liver sections was performed to analyze expression profiles of CAPERα, VEGF and CD34 in HCC and control tissues and was further used to assess the correlation of expression among CAPERα, VEGF and CD34 in HCC development.
Autoantibody to CAPERα was highest in HCC (22/76, 28.9%), not detected in prostate cancer (0/79) and at 3.4% (3/88) in breast cancer. In immunohistochemical analysis of grades II and III HCC tissues, significantly decreased immunostaining for CAPERα was observed and this correlated directly with decreased immunostaining for VEGF (R=0.534, P=0.0003). Using CD34 immunostaining for detecting newly formed microvessels, strong staining was observed in grades II and III HCC. Normal liver sections, all of which have high expression of CAPERα were totally negative for CD34 immunostaining. A significant inverse correlation was seen between CAPERα and CD34 immunostaining (R=-0.481, P=0.0012).
Decreased expression of CAPERα appears to be correlated with appearance of microvessels. It would be of interest to elucidate the cause of altered CAPERα since new formation of microvessels is important in progression of HCC.
Caperα是一种肿瘤相关抗原，从一名肝细胞癌（HCC）患者的含自身抗体的cDNA克隆中被鉴定出来。通过血管内皮生长因子（VEGF）前体信使核糖核酸（mRNA）的可变剪接，它参与了尤因肉瘤中微血管形成的调控。在本研究中，我们探究了Caperα改变与HCC中微血管密度之间可能存在的关联。
使用重组Caperα作为抗原的酶联免疫吸附测定法来检测抗Caperα抗体。对肝组织切片进行免疫组织化学（IHC）分析，以分析HCC组织和对照组织中Caperα、VEGF和CD34的表达谱，并进一步用于评估HCC发生过程中Caperα、VEGF和CD34表达之间的相关性。
抗Caperα自身抗体在HCC中最高（22/76，28.9%），在前列腺癌中未检测到（0/79），在乳腺癌中为3.4%（3/88）。在II级和III级HCC组织的免疫组织化学分析中，观察到Caperα的免疫染色显著降低，且这与VEGF免疫染色的降低直接相关（R = 0.534，P = 0.0003）。使用CD34免疫染色检测新生微血管，在II级和III级HCC中观察到强染色。所有Caperα高表达的正常肝组织切片CD34免疫染色均为阴性。Caperα与CD34免疫染色之间存在显著负相关（R = -0.481，P = 0.0012）。
Caperα表达降低似乎与微血管的出现相关。鉴于微血管的新生在HCC进展中很重要，阐明Caperα改变的原因将是有意义的。
