Purpose: Lipid metabolism reprogramming is a major pathway in tumor evolution. This study investigated fatty acid synthase (FASN) mRNA expression in anthropometric adipose tissue and elucidated the prognostic value and potential mechanism of clear cell renal cell carcinoma (ccRCC).

Materials and Methods: Transcription profiles were obtained from 533 ccRCC samples in The Cancer Genome Atlas (TCGA) cohorts. Real-time quantitative PCR (RT-qPCR) and immunohistochemistry were performed to detect FASN expression in 380 paired ccRCC and normal tissues from the Fudan University Shanghai Cancer Center (FUSCC). Visceral adipose tissue (VAT) and subcutaneous adipose tissue were at the level of the umbilicus as measured by magnetic resonance imaging (MRI). Non-targeted metabolomics and in vitro experiments were used to reveal the biological functions of FASN.

Results: Increased FASN expression was significantly relevant to advanced T, N, and American Joint Committee on Cancer (AJCC) stages (p < 0.01) and significantly correlated to poor progression-free survival (PFS) and overall survival (OS) of 913 ccRCC patients in FUSCC and TCGA cohorts. Pearson's correlation coefficient indicated that FASN amplification was positively correlated to VAT% (r = 0.772, p < 0.001), which significantly correlated to poor PFS (HR = 2.066, p = 0.028) and OS (HR = 2.773, p = 0.023) in the FUSCC cohort. Transient inhibition or overexpression of FASN significantly regulated A498 and 786O cell proliferation and migration by regulating epithelial–mesenchymal transition. Inhibition of FASN led to a higher apoptotic rate and decreased lipid droplet formation compared with normal control in ccRCC cells. Non-targeted metabolomics showed that decreased de novo lipogenesis might be required to sustain an elevation of glycolytic activity in 786O cells by regulating galactinol, dl-lactate, N-acetylaspartylglutamate, and sucrose, thereby participating in carcinogenesis and progression of ccRCC.

Conclusion: This study demonstrated that FASN expression is positively related to aggressive cell proliferation, migration, apoptosis, and lipid droplet formation and regulates metabolic disorders of the ccRCC microenvironment. Additionally, elevated FASN mRNA expression is significantly correlated to the abdominal obesity distribution, especially VAT%, which is a significant predictor of a poor prognosis for ccRCC patients.

目的：脂质代谢重编程是肿瘤进化中的主要途径。这项研究调查了人体脂肪组织中脂肪酸合酶（FASN）mRNA的表达，并阐明了透明细胞肾细胞癌（ccRCC）的预后价值和潜在机制。

材料和方法：从癌症基因组图谱（TCGA）队列中的533个ccRCC样本获得了转录谱。进行实时定量PCR（RT-qPCR）和免疫组化检测财务会计准则复旦大学附属上海癌症中心（FUSCC）在380个配对ccRCC和正常组织中的表达。通过磁共振成像（MRI）测量，内脏脂肪组织（VAT）和皮下脂肪组织处于脐带水平。非靶向代谢组学和体外 实验被用来揭示FASN的生物学功能。

结果： 增加 财务会计准则 表达与晚期T，N和美国癌症联合委员会（AJCC）阶段显着相关（p<0.01），并且与FUSCC和TCGA队列中913 ccRCC患者的不良无进展生存期（PFS）和总体生存期（OS）显着相关。皮尔逊的相关系数表明财务会计准则 扩增与VAT％正相关（[R = 0.772， p <0.001），这与PFS差（HR = 2.066， p = 0.028）和操作系统（HR = 2.773， p= 0.023）。瞬时抑制或过度表达财务会计准则通过调节上皮-间质转化显着调节A498和786O细胞的增殖和迁移。抑制财务会计准则与正常对照组相比，可导致ccRCC细胞凋亡率更高，脂质滴形成减少。非靶向代谢组学显示下降从头 可能需要通过调节半乳糖半乳糖脂来维持786O细胞糖酵解活性的升高。 dl-乳酸，N-乙酰基天冬氨酰谷氨酸和蔗糖，从而参与ccRCC的癌变和发展。

结论： 这项研究表明 财务会计准则表达与侵袭性细胞增殖，迁移，凋亡和脂质滴形成呈正相关，并调节ccRCC微环境的代谢异常。此外，高架财务会计准则 mRNA表达与腹部肥胖分布尤其是VAT％显着相关，这是ccRCC患者预后不良的重要预测指标。