Tolkach Yuri, Lüders Christine, Meller Sebastian, Jung Klaus, Stephan Carsten, Kristiansen Glen
Institute for Pathology, University Hospital Bonn, Bonn, Germany.
Berlin Institute of Urologic Research, Berlin, Germany.
Oncotarget. 2017 Apr 25;8(17):28672-28682. doi: 10.18632/oncotarget.15639.
To study the expression of adipophilin (PLIN2), a lipid storage-associated cell protein, in different subtypes of renal cell cancer and to elucidate its prognostic value.
Two-hundred-seventy-five patients with renal cell carcinoma (RCC) were included in this study. Immunohistochemistry with a polyclonal antibody to adipophilin was used on the tissue microarray (formalin-fixed, paraffin-embedded tissue) for detection of adipophilin. Median follow-up time was 91 (range 1-159) months in the whole cohort and 100 (1-159) months for patients with clear-cell RCC. Additional validation for adipophilin was performed using publicly available gene expression data for clear cell RCC from The Cancer Genome Atlas (TCGA).
Adipophilin expression was detected in 14.3% of papillary RCC, in 0% of chromophobe RCC and in 58.7% of clear-cell RCC in the cytoplasm or at the membrane. Only membrane expression was correlated with other clinical parameters (pT-stage, pN-stage, R-status, sex) and showed a prognostic significance in univariate analysis with regard to overall survival of patients with clear cell subtype (HR 2.90, 95% CI 1.55-5.42, p=0.001), which failed significance on multivariate analysis. mRNA expression of PLIN2 on TCGA data using best selected cut-off was prognostically significant in both univariate (HR 1.76, 95% CI 1.28-2.42, p = 0.0005) and multivariate analyses (HR 1.46, 95% CI 1.05-2.04, p = 0.0257).
Adipophilin is a novel and still understudied prognostic biomarker in clear cell renal cell carcinoma which deserves further study.
研究脂质储存相关细胞蛋白脂滴结合蛋白（PLIN2）在不同亚型肾细胞癌中的表达情况，并阐明其预后价值。
本研究纳入了275例肾细胞癌（RCC）患者。使用抗脂滴结合蛋白的多克隆抗体对组织芯片（福尔马林固定、石蜡包埋组织）进行免疫组织化学检测，以检测脂滴结合蛋白。整个队列的中位随访时间为91（范围1 - 159）个月，透明细胞RCC患者的中位随访时间为100（1 - 159）个月。使用来自癌症基因组图谱（TCGA）的透明细胞RCC的公开可用基因表达数据对脂滴结合蛋白进行了额外验证。
在14.3%的乳头状RCC、0%的嫌色性RCC以及58.7%的透明细胞RCC的细胞质或细胞膜中检测到脂滴结合蛋白表达。仅细胞膜表达与其他临床参数（pT分期、pN分期、R状态、性别）相关，并且在单因素分析中对透明细胞亚型患者的总生存显示出预后意义（HR 2.90，95% CI 1.55 - 5.42，p = 0.001），但在多因素分析中未显示出显著性。使用最佳选择的临界值，基于TCGA数据的PLIN2 mRNA表达在单因素（HR 1.76，95% CI 1.28 - 2.42，p = 0.0005）和多因素分析（HR 1.46，95% CI 1.05 - 2.04，p = 0.0257）中均具有预后意义。
脂滴结合蛋白是透明细胞肾细胞癌中一种新型且仍未被充分研究的预后生物标志物，值得进一步研究。
