Prognostic signatures of sphingolipids: Understanding the immune landscape and predictive role in immunotherapy response and outcomes of hepatocellular carcinoma

• DOI: 10.3389/fimmu.2023.1153423
• Publication Date: 2023-03-17T04:44:16Z
• Authors: Xin Zhang; Jinke Zhuge; Jinhui Liu; Zhijia Xia; Huixiong Wang; Qiang Gao; Hao Jiang; Yanyu Qu; Linlin Fan; Jiali Ma; Chunhua Tan; Wei Luo; Yong Luo
• Keywords: Gene signature; Nomogram; Sphingolipid

Hepatocellular carcinoma (HCC) is a complex disease with poor outlook for patients in advanced stages. Immune cells play an important role the progression of HCC. The metabolism sphingolipids functions both tumor growth and immune infiltration. However, little research has focused on using sphingolipid factors to predict HCC prognosis. This study aimed identify key genes (SPGs) develop reliable prognostic model based these genes.The TCGA, GEO, ICGC datasets were grouped SPGs obtained from InnateDB portal. A gene signature was created by applying LASSO-Cox analysis evaluating it Cox regression. validity verified GEO datasets. microenvironment (TME) examined ESTIMATE CIBERSORT, potential therapeutic targets identified through machine learning. Single-cell sequencing used examine distribution within TME. Cell viability migration tested confirm SPGs.We 28 that have impact survival. Using clinicopathological features 6 genes, we developed nomogram high- low-risk groups found distinct characteristics response drugs. Unlike CD8 T cells, M0 M2 macrophages be highly infiltrated TME high-risk subgroup. High levels good indicator immunotherapy. In cell function experiments, SMPD2 CSTA enhance survival Huh7 while silencing increased sensitivity lapatinib.The presents six-gene can aid clinicians choosing personalized treatments patients. Furthermore, uncovers connection between sphingolipid-related microenvironment, offering novel approach By focusing crucial like CSTA, efficacy anti-tumor therapy cells.