Department of Surgery, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8605, Japan.
Advanced Comprehensive Research Organization (ACRO), Teikyo University, Tokyo, Japan.
Sci Rep. 2023 Sep 27;13(1):16249. doi: 10.1038/s41598-023-43557-1.
Ceramide, the central molecule in sphingolipid synthesis, is a bioactive lipid that serves as a regulatory molecule in the anti-inflammatory responses, apoptosis, programmed necrosis, autophagy, and cell motility of cancer cells. In particular, the authors have reported differences in sphingolipid content in colorectal cancer tissues. The associations among genetic mutations, clinicopathological factors, and sphingolipid metabolism in colorectal cancer (CRC) have not been investigated. The objective of this study is to investigate the association between genes associated with sphingolipid metabolism, genetic variations in colorectal cancer (CRC), and clinicopathological factors in CRC patients. We enrolled 82 consecutive patients with stage I-IV CRC who underwent tumor resection at a single institution in 2019-2021. We measured the expression levels of genes related to sphingolipid metabolism and examined the relationships between CRC gene mutations and the clinicopathological data of each individual patient. The relationship between CRC gene mutations and expression levels of ceramide synthase (CERS), N-acylsphingosine amidohydrolase (ASAH), and alkaline ceramidase (ACER) genes involved in sphingolipid metabolism was examined CRES4 expression was significantly lower in the CRC KRAS gene mutation group (p = 0.004); vascular invasion was more common in colorectal cancer patients with high CERS4 expression (p = 0.0057). By examining the correlation between sphingolipid gene expression and clinical factors, we were able to identify cancer types in which sphingolipid metabolism is particularly relevant. CERS4 expression was significantly reduced in KRAS mutant CRC. Moreover, CRC with decreased CERS4 showed significantly more frequent venous invasion.
神经酰胺是神经鞘脂合成的核心分子，是一种具有生物活性的脂质，作为一种调节分子参与癌细胞的抗炎反应、细胞凋亡、程序性坏死、自噬和细胞运动。特别是，作者已经报道了结直肠癌组织中神经鞘脂含量的差异。遗传突变、临床病理因素与结直肠癌（CRC）中神经鞘脂代谢之间的关系尚未得到研究。本研究旨在探讨与神经鞘脂代谢相关的基因、CRC 中的遗传变异与 CRC 患者临床病理因素之间的关系。我们纳入了 2019-2021 年在单一机构接受肿瘤切除术的 82 例 I-IV 期 CRC 连续患者。我们测量了与神经鞘脂代谢相关的基因的表达水平，并检查了 CRC 基因突变与每位患者的临床病理数据之间的关系。检查了 CRC 基因突变与神经鞘脂代谢相关基因（CERs）、N-酰基鞘氨醇酰胺水解酶（ASAH）和碱性神经酰胺酶（ACER）的表达水平之间的关系。CERs4 的表达在 CRC KRAS 基因突变组中显著降低（p=0.004）；在 CERS4 高表达的结直肠癌患者中，血管侵犯更为常见（p=0.0057）。通过检查神经鞘脂基因表达与临床因素之间的相关性，我们能够确定与神经鞘脂代谢特别相关的癌症类型。在 KRAS 突变型 CRC 中 CERS4 的表达显著降低。此外，CERS4 减少的 CRC 显示出明显更频繁的静脉侵犯。
