Department of Urology, Huashan Hospital, Fudan University, Shanghai, 200040, PR China; Fudan Institute of Urology, Shanghai, 200040, PR China.
Department of Urology, Huashan Hospital, Fudan University, Shanghai, 200040, PR China; Fudan Institute of Urology, Shanghai, 200040, PR China.
Biochem Biophys Res Commun. 2018 Sep 10;503(3):1537-1543. doi: 10.1016/j.bbrc.2018.07.076. Epub 2018 Jul 20.
Clear-cell renal cell carcinoma (ccRCC) is characterized with underlying genetic disorders and the role of low density lipoprotein receptor-related protein 1 (LRP1) in ccRCC is unknown.
An in silico exploratory analysis using multiple public genetic datasets was used to establish association between LRP1 expression and clinicopathological parameters. Associations of interest were validated using 155 ccRCC samples using immunohistochemistry.
LRP1 was overexpressed in tumor compared with normal kidney tissue. Increased LRP1 expression in ccRCC was associated with advanced stage, grade and worsened overall survival and progression-free survival. Functional annotation indicated an immune-modulatory role of LRP1 in ccRCC. LRP1 expression was significantly correlated with expressions of PBRM1, SETD2, and KDM5C. Positive correlations between LRP1 and pro-angiogenic factors ERAP1, SCG2, STAB1, and RUNX1 were observed. LRP1 expression was positively correlated with PD-L2 level. Negative correlations between LRP1 and anti-angiogenic factors EMCN and IL18 were observed. LRP1 expression was not associated with microvessel density (MVD) yet was negatively correlated with tumor-infiltrating lymphocytes (TIL).
LRP1 is associated with worsened prognosis in ccRCC and is related to cancer immune modulation. LRP1-targeted therapy can be of therapeutic potential.
透明细胞肾细胞癌（ccRCC）的特征是潜在的遗传紊乱，而低密度脂蛋白受体相关蛋白 1（LRP1）在 ccRCC 中的作用尚不清楚。
使用多个公共遗传数据集进行的计算机探索性分析，用于建立 LRP1 表达与临床病理参数之间的关联。使用免疫组织化学方法在 155 个 ccRCC 样本中验证了感兴趣的关联。
与正常肾组织相比，LRP1 在肿瘤中过度表达。ccRCC 中 LRP1 的表达增加与晚期、高等级和更差的总生存期和无进展生存期相关。功能注释表明 LRP1 在 ccRCC 中具有免疫调节作用。LRP1 表达与 PBRM1、SETD2 和 KDM5C 的表达显著相关。观察到 LRP1 与促血管生成因子 ERAP1、SCG2、STAB1 和 RUNX1 之间存在正相关。LRP1 表达与 PD-L2 水平呈正相关。观察到 LRP1 与抗血管生成因子 EMCN 和 IL18 之间存在负相关。LRP1 表达与微血管密度（MVD）无关，但与肿瘤浸润淋巴细胞（TIL）呈负相关。
LRP1 与 ccRCC 预后恶化相关，并与癌症免疫调节有关。LRP1 靶向治疗具有治疗潜力。
