Department of Pediatric Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, 250014, China.
Department of Pathology, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, 250014, China.
Pathol Res Pract. 2020 Nov;216(11):153227. doi: 10.1016/j.prp.2020.153227. Epub 2020 Sep 28.
Fatty acid synthase (FASN), a key enzyme essential for fatty acid (FA) synthesis, was reportedly implicated in the initiation and progression of various cancers. However, the clinical significance of FASN in renal cell carcinoma (RCC) has not been fully elucidated yet. Here we compare the expression profile and evaluate the prognostic significance of FASN in clear cell RCC (ccRCC) patients. FASN expression was examined in 3 pairs ccRCC and their adjacent nontumor tissues by western blotting (WB) analysis, and its expression was assessed in 145 ccRCC and 13 nontumor tissues by immunohistochemistry (IHC) analysis with tissue microarrays (TMAs). The prognosis of FASN was further investigated in large-scale database using LinkedOmics (n = 537) and The Cancer Protein Atlas (TCPA, n = 445), respectively. WB detected higher FASN expression in ccRCC than normal tissues, then IHC analysis revealed that FASN expression was positively associated with histological grade, pathological stage, tumor size and metastasis status, and negatively associated with cancer-specific survival (CSS). Univariate survival analysis demonstrated that high grade, advanced stage, large tumor, metastasis, and high FASN expression were significantly associated with a shorter CSS, and multivariate analysis revealed tumor grade, stage, metastasis and FASN were identified as independent predictors for CSS in patients with ccRCC. Further LinkedOmics and TCPA analyses confirmed that high FASN expression was correlated with a poorer overall survival (OS) of ccRCC. Collectively, these findings demonstrated FASN could be a poor prognostic factor in ccRCC patients, which indicated that FA synthesis might be implicated in the tumorigenesis and progression of ccRCC.
脂肪酸合酶（FASN）是脂肪酸（FA）合成所必需的关键酶，据报道其参与了各种癌症的发生和发展。然而，FASN 在肾细胞癌（RCC）中的临床意义尚未完全阐明。在这里，我们比较了 FASN 在透明细胞 RCC（ccRCC）患者中的表达谱，并评估了其预后意义。通过 Western blot（WB）分析检测了 3 对 ccRCC 及其相邻非肿瘤组织中的 FASN 表达，并通过组织微阵列（TMA）的免疫组织化学（IHC）分析评估了 145 例 ccRCC 和 13 例非肿瘤组织中的 FASN 表达。使用 LinkedOmics（n = 537）和 The Cancer Protein Atlas（TCPA，n = 445）分别在大规模数据库中进一步研究了 FASN 的预后。WB 检测到 ccRCC 中的 FASN 表达高于正常组织，然后 IHC 分析表明 FASN 表达与组织学分级、病理分期、肿瘤大小和转移状态呈正相关，与癌症特异性生存（CSS）呈负相关。单因素生存分析表明，高级别、晚期、大肿瘤、转移和高 FASN 表达与 CSS 较短显著相关，多因素分析表明肿瘤分级、分期、转移和 FASN 是 ccRCC 患者 CSS 的独立预测因子。进一步的 LinkedOmics 和 TCPA 分析证实，高 FASN 表达与 ccRCC 的总体生存（OS）较差相关。总之，这些发现表明 FASN 可能是 ccRCC 患者的预后不良因素，这表明 FA 合成可能参与了 ccRCC 的肿瘤发生和进展。
