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

Abstract

Background The 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. Methods HCC 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. Results Through 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. Conclusions CD5L, 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.

Prognostic significance of LRRC1 in hepatocellular carcinoma and construction of relevant prognostic model

“…CD5L presented with abnormal mRNA and protein levels in HCC and it was found to be an independent prognostic factor for HCC patients. [63,64] DAB2 promotes epithelial-mesenchymal transition and invasion of tumor cells at advanced tumor stages, and it acts as a risk factor in HCC, [65] which is consistent with our findings. High expression of IMPDH1 is associated with poor prognosis of HCC patients and may serve as a potential target for immunotherapy.…”

Identification and functional analysis of lactic acid metabolism-related differentially expressed genes in hepatocellular carcinoma

“…Reducing CCNB1 expression can suppresses the growth of HCC cells ( Li et al, 2021 ). LCAT has been reported as a prognostic and recurrence biomarker in HCC ( Long et al, 2019 ; Hu et al, 2020 ; Jiang et al, 2020 ; Su et al, 2021 ; Sharifi et al, 2022 ) and has been correlated to anti-cancer drug sensitivities ( Zhang et al, 2022 ). Collectively, LAMRDEGs may serves as prognostic biomarkers and potential targets for the development of new therapeutic strategies for HCC.…”

Disulfidptosis-related signature predicts prognosis and characterizes the immune microenvironment in hepatocellular carcinoma

“…LCAT is abundantly expressed in the human body and has low expression in breast cancer and liver cancer tissue that in compared to normal tissue, but high expression in the serum of advanced breast cancer, suggesting that LCAT may serve as a plasma protein biomarker for late-stage breast cancer and metastasis [ 23 ]. In contrast, LCAT levels are lower in the serum of colorectal cancer, liver cancer, and ovarian cancer patients, making it a potential biomarker [ 24 – 26 ].…”