Dinarvand Negar, Khanahmad Hossein, Hakimian Sayyed Mohammadreza, Sheikhi Abdolkarim, Rashidi Bahman, Pourfarzam Morteza
Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R. Iran.
Department of Genetic and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, I.R. Iran.
Res Pharm Sci. 2020 Feb 20;15(1):48-56. doi: 10.4103/1735-5362.278714. eCollection 2020 Feb.
Breast cancer (BC) is one of the major causes of female cancer-related death. It has recently been demonstrated that metabolic reprogramming including alteration in lipid metabolism is indicated in various types of cancer. The enzymes of the acyl-coenzyme A synthetase long-chain family (ACSLs) are responsible for converting fatty acids to their corresponding fatty acyl-coenzyme A esters which are essential for some lipid metabolism pathways. ACSL4 is one of the isoforms of ACSLs and has a marked preference for arachidonic and eicosapentaenoic acids. The objective of this study was to evaluate ACSL4 expression, its prognostic significance, and its correlation with p53 tumor suppressor in BC patients.
In this study 55 pairs of fresh samples of BC and adjacent non-cancerous tissue were used to analyze ACSL4 expression, using real-time polymerase chain reaction and immunohistochemistry (IHC) staining. The expression of other studied variables was also examined using the IHC technique.
FINDINGS / RESULTS: ACSL4 expression was significantly higher in BC tissues compared to the adjacent normal tissue. This upregulation was negatively correlated with Ki-67 and age, and positively correlated with p53 status. The correlation between ACSL4 and p53 may indicate the role of p53 in the regulation of lipid metabolism in cancer cells, in addition to its role in the regulation of ferroptosis cell death.
Our results indicated that the expression of ACSL4 may be considered as a prognostic indicator and potential therapeutic target in BC. However, further studies are needed to confirm the significance of these findings.
乳腺癌（BC）是女性癌症相关死亡的主要原因之一。最近有研究表明，包括脂质代谢改变在内的代谢重编程在多种类型的癌症中均有体现。酰基辅酶A合成酶长链家族（ACSLs）的酶负责将脂肪酸转化为相应的脂肪酰基辅酶A酯，这对某些脂质代谢途径至关重要。ACSL4是ACSLs的亚型之一，对花生四烯酸和二十碳五烯酸有明显偏好。本研究的目的是评估BC患者中ACSL4的表达、其预后意义以及与p53肿瘤抑制因子的相关性。
在本研究中，使用55对新鲜的BC组织和相邻非癌组织样本，通过实时聚合酶链反应和免疫组织化学（IHC）染色分析ACSL4的表达。其他研究变量的表达也采用IHC技术进行检测。
与相邻正常组织相比，BC组织中ACSL4的表达显著更高。这种上调与Ki-67和年龄呈负相关，与p53状态呈正相关。ACSL4与p53之间的相关性可能表明p53除了在调节铁死亡细胞死亡中的作用外，还在癌细胞脂质代谢调节中发挥作用。
我们的结果表明，ACSL4的表达可被视为BC的预后指标和潜在治疗靶点。然而，需要进一步研究来证实这些发现的意义。
