CD5L-associated gene analyses highlight the dysregulations, prognostic effects, immune associations, and drug-sensitivity predicative potentials of LCAT and CDC20 in hepatocellular carcinoma

Cancer Cell International

Research

Keke Zhu¹  Tao Sun¹  Ningning Li¹  Xiuzhi Zhang¹  Jinzhong Zhang¹  Liping Dai²  Xue Zhang²  Xiaoli Liu³  Shasha Fan⁴ 

[1] Department of Pathology, Henan Medical College, Zhengzhou, China;Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China;Laboratory Department, Henan Provincial People’s Hospital, Zhengzhou, China;Oncology Department, The First Affiliated Hospital of Hunan Normal University, Hunan Provincial People’s Hospital, Changsha, China;Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Hunan Normal University, Changsha, China;

关键词: CD5L;    LCAT;    CDC20;    Hepatocellular carcinoma (HCC);    Lipid metabolism;    Immune response;    Diagnosis;    Prognosis;   

DOI  :  10.1186/s12935-022-02820-7

 received in 2022-05-30, accepted in 2022-12-01,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundThe dysregulation of CD5L has been reported in hepatocellular carcinoma (HCC). However, its functions in HCC were controversial. In this study, we aimed to identify CD5L-associated pathways and markers and explore their values in HCC diagnosis, prognosis and treatment.MethodsHCC datasets with gene expression profiles and clinical data in TCGA and ICGC were downloaded. The immune/stroma cell infiltrations were estimated with xCell. CD5L-associated pathways and CD5L-associated genes (CD5L-AGs) were identified with gene expression comparisons and gene set enrichment analysis (GSEA). Cox regression, Kaplan–Meier survival analysis, and least absolute shrinkage and selection operator (LASSO) regression analysis were performed. The correlations of the key genes with immune/stroma infiltrations, immunoregulators, and anti-cancer drug sensitivities in HCC were investigated. At protein level, the key genes dysregulations, their correlations and prognostic values were validated in clinical proteomic tumor analysis consortium (CPTAC) database. Serum CD5L and LCAT activity in 50 HCC and 30 normal samples were evaluated and compared. The correlations of serum LCAT activity with alpha-fetoprotein (AFP), albumin (ALB) and high-density lipoprotein (HDL) in HCC were also investigated.ResultsThrough systemic analyses, 14 CD5L-associated biological pathways, 256 CD5L-AGs and 28 CD5L-associated prognostic and diagnostic genes (CD5L-APDGs) were identified. A risk model consisting of LCAT and CDC20 was constructed for HCC overall survival (OS), which could discriminate HCC OS status effectively in both the training and the validation sets. CD5L, LCAT and CDC20 were shown to be significantly correlated with immune/stroma cell infiltrations, immunoregulators and 31 anti-cancer drug sensitivities in HCC. At protein level, the dysregulations of CD5L, LCAT and CDC20 were confirmed. LCAT and CDC20 were shown to be significantly correlated with proliferation marker MKI67. In serum, no significance of CD5L was shown. However, the lower activity of LCAT in HCC serum was obvious, as well as its significant positive correlations ALB and HDL concentrations.ConclusionsCD5L, LCAT and CDC20 were dysregulated in HCC both at mRNA and protein levels. The LCAT-CDC20 signature might be new predicator for HCC OS. The associations of the three genes with HCC microenvironment and anti-cancer drug sensitivities would provide new clues for HCC immunotherapy and chemotherapy.

【 授权许可】

CC BY   
© The Author(s) 2022

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