Identification of LEA, a podocalyxin-like glycoprotein, as a predictor for the progression of colorectal cancer.
Identification of LEA, a podocalyxin-like glycoprotein, as a predictor for the progression of colorectal cancer.
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DOI：
10.1002/cam4.1765
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发表时间：
2018-10
期刊：
影响因子：
4
通讯作者：
Fang J
中科院分区：
文献类型：
--
作者：
Yuan D;Chen H;Wang S;Liu F;Cheng Y;Fang J
大外抗原（Large external antigen， LEA）被认为是结直肠癌（CRC）相关抗原，通过杂交瘤技术生成的单抗ND - 1发现，但其分子特征尚不清楚。为了促进LEA的临床应用，我们利用免疫沉淀和质谱联合鉴定LEA为分子量约为230 kDa的高糖基化蛋白podocalyxin - like protein 1 (PODXL)，并证实ND - 1识别的表位位于LEA的末端唾液酸上。LEA与PODXL在分子量、免疫交叉反应性和基因表达依赖性方面的相关性分析支持LEA的PODXL身份。此外，我们利用量子点免疫组化（QD‐IHC）方法，利用ND‐1评估了LEA在89对原发性结直肠癌组织和邻近非肿瘤结直肠癌组织中的临床意义。LEA高表达与T分期有显著相关性（P = 0.010）。LEA高表达患者预后明显差于LEA低表达患者（P = 0.007）。多因素分析显示LEA表达为独立预测因子。此外，对比分析表明，在CRC细胞系和临床样品中，基于mAb ND‐1的PODXL糖残基免疫组化分析比基于mAb 3D3的PODXL核心蛋白免疫组化分析具有更高的敏感性和特异性。此外，我们首次发现LEA/PODXL可以在癌细胞和CRC患者外周血的外泌体中分泌。我们的研究结果表明，LEA是CRC进展的独立预测因子，具有高敏感性、高特异性和无创进入的临床应用潜力。
Large external antigen (LEA) is considered as a colorectal cancer (CRC)‐associated antigen, which was found via mAb ND‐1 generated using hybridoma technology, but its molecular features remain unknown. To facilitate the clinical application of LEA, we identified LEA as a podocalyxin‐like protein 1 (PODXL) with molecular weight of approximately 230 kDa, a hyperglycosylated protein, using immunoprecipitation and mass spectrometry in combination, and verified that ND‐1‐recognized epitope is on the terminal sialic acid of LEA. Correlation analysis between LEA and PODXL in molecular weight, immunological cross‐reactivity, and gene expression dependence supported the PODXL identity of the LEA. Moreover, we assessed the clinical significance of the LEA in 89 pairs of primary CRC tissues and adjacent nontumor colorectal tissues using ND‐1 by quantum dot‐based immunohistochemistry (QD‐IHC). High LEA expression was correlated significantly with T stage (P = 0.010). Patients with high LEA expression showed significantly poorer prognosis than those with LEA low expression (P = 0.007). Multivariate analysis indicated LEA expression as an independent predictor. Furthermore, the comparative analysis showed that mAb ND‐1‐based IHC analysis toward sugar residue of PODXL has higher sensitivity and specificity to evaluate the LEA/PODXL expression than mAb 3D3‐based method toward core protein of PODXL in CRC cell lines and clinical samples. In addition, we first found that LEA/PODXL can be secreted in exosomes from cancer cells and CRC patient peripheral blood. Our results demonstrate that LEA is an independent predictor for CRC progression and has the potential to be applied for clinical setting with high sensitivity, high specificity, and noninvasive access.
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影响因子：
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作者：
Borg D;Hedner C;Nodin B;Larsson A;Johnsson A;Eberhard J;Jirström K
通讯作者：
Jirström K
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Jou, TS
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通讯作者：
Jirström K
影响因子：
8.8
作者：
Larsson, A.;Johansson, M. E.;Wangefjord, S.;Gaber, A.;Nodin, B.;Kucharzewska, P.;Welinder, C.;Belting, M.;Eberhard, J.;Johnsson, A.;Uhlen, M.;Jirstrom, K.
通讯作者：
Jirstrom, K.