Lin Tong, Zhang E, Lin Zhimei, Peng Lisheng
The Fourth Clinical Medical School, Guangzhou University of Chinese Medicine, Shenzhen, People's Republic of China.
Department of Science and Education, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, People's Republic of China.
Int J Gen Med. 2021 Nov 30;14:9117-9130. doi: 10.2147/IJGM.S344723. eCollection 2021.
The prognosis of patients with advanced hepatocellular carcinoma (HCC) remains poor. Lipid remodeling modulators are considered promising therapeutic targets of cancers, owing to their functions of facilitating cancer cells' adaption to the limited environment. Lysophosphatidylcholine acyltransferases (LPCATs) are enzymes regulating bio-membrane remodeling, whose roles in HCC have not been fully illuminated.
Multiple bioinformatic tools were applied to comprehensively evaluate the expression, genetic alterations, clinical relevance, prognostic values, DNA methylation, biological functions, and correlations with immune infiltration of LPCATs in HCC.
We found was significantly overexpressed and the most frequently altered in HCC. The high-expression of indicated clinicopathological advancements and poor prognoses of HCC patients. Even though the global DNA methylation of LPCATs in HCC showed no significant difference with that in normal liver, the hypermethylation of numerous CpG sites of them implied worse survivals of HCC patients. Thirty LPCATs' interactive genes were identified, which were generally membrane components and partook in phospholipid metabolism pathways. Finally, we found the expression of LPCATs was extensively positively correlated with the infiltration of various stimulatory and suppressive tumor-infiltrating immune cells (TIICs) in the tumor microenvironment.
This study addressed LPCAT1/4 were potential prognostic and immunotherapeutic biomarkers of HCC targeting bio-membrane lipid remodeling.
晚期肝细胞癌(HCC)患者的预后仍然很差。脂质重塑调节剂由于其促进癌细胞适应有限环境的功能,被认为是有前景的癌症治疗靶点。溶血磷脂酰胆碱酰基转移酶(LPCATs)是调节生物膜重塑的酶,其在HCC中的作用尚未完全阐明。
应用多种生物信息学工具综合评估LPCATs在HCC中的表达、基因改变、临床相关性、预后价值、DNA甲基化、生物学功能以及与免疫浸润的相关性。
我们发现 在HCC中显著过表达且是最常发生改变的。 的高表达表明HCC患者的临床病理进展和预后不良。尽管HCC中LPCATs的整体DNA甲基化与正常肝脏相比无显著差异,但它们众多CpG位点的高甲基化意味着HCC患者的生存期更差。鉴定出30个LPCATs的相互作用基因,它们通常是膜成分并参与磷脂代谢途径。最后,我们发现LPCATs的表达与肿瘤微环境中各种刺激性和抑制性肿瘤浸润免疫细胞(TIICs)的浸润广泛正相关。
本研究表明LPCAT1/4是靶向生物膜脂质重塑的HCC潜在预后和免疫治疗生物标志物。