Establishment and validation of a cholesterol metabolism-related prognostic signature for hepatocellular carcinoma

Tang, Linsong; Wei, Ran; Chen, Ronggao; Fan, Guanghan; Zhou, Junbin; Qi, Zhetuo; Wang, Kai; Wei, Qiang; Wei, Xuyong; Xu, Xiao Chun

doi:10.1016/j.csbj.2022.07.030

Cited by 22 publications

(20 citation statements)

References 63 publications

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“…3 C–D). We also compared our signature with 10 other established prognostic signatures, including the Zhao signature [ 27 ], Liu signature [ 28 ], Fu signature [ 29 ], Wang signature[ 30 ], Zhigang signature [ 31 ], Yang signature [ 32 ], Liang signature [ 33 ], Tang signature [ 34 ], Li signature [ 35 ], and Tian signature [ 36 ]. Interestingly, our TRPS had the highest C-index compared with these 10 established prognostic signatures, suggesting that our TRPS had a relatively better performance in predicting the prognosis of HCC than some of the other signatures (Fig.…”

Section: Resultsmentioning

confidence: 99%

A T-cell-related signature for prognostic stratification and immunotherapy response in hepatocellular carcinoma based on transcriptomics and single-cell sequencing

et al. 2023

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Background Hepatocellular carcinoma (HCC) is the fifth most frequently diagnosed malignancy and the third leading cause of cancer death globally. T cells are significantly correlated with the progression, therapy and prognosis of cancer. Limited systematic studies regarding the role of T-cell-related markers in HCC have been performed. Methods T-cell markers were identified with single-cell RNA sequencing (scRNA-seq) data from the GEO database. A prognostic signature was developed with the LASSO algorithm in the TCGA cohort and verified in the GSE14520 cohort. Another three eligible immunotherapy datasets, GSE91061, PRJEB25780 and IMigor210, were used to verify the role of the risk score in the immunotherapy response. Results With 181 T-cell markers identified by scRNA-seq analysis, a 13 T-cell-related gene-based prognostic signature (TRPS) was developed for prognostic prediction, which divided HCC patients into high-risk and low-risk groups according to overall survival, with AUCs of 1 year, 3 years, and 5 years of 0.807, 0.752, and 0.708, respectively. TRPS had the highest C-index compared with the other 10 established prognostic signatures, suggesting a better performance of TRPS in predicting the prognosis of HCC. More importantly, the TRPS risk score was closely correlated with the TIDE score and immunophenoscore. The high-risk score patients had a higher percentage of SD/PD, and CR/PR occurred more frequently in patients with low TRPS-related risk scores in the IMigor210, PRJEB25780 and GSE91061 cohorts. We also constructed a nomogram based on the TRPS, which had high potential for clinical application. Conclusion Our study proposed a novel TRPS for HCC patients, and the TRPS could effectively indicate the prognosis of HCC. It also served as a predictor for immunotherapy.

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Section: Resultsmentioning

confidence: 99%

A T-cell-related signature for prognostic stratification and immunotherapy response in hepatocellular carcinoma based on transcriptomics and single-cell sequencing

et al. 2023

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“…With the advancement of genomics, a growing number of genetic markers have been uncovered, and these biomarkers have dramatically contributed to cancer research in terms of diagnosis, treatment and prognosis assessment. [18][19][20] In our project, we explored the significance of PRGs in CC utilizing two independent CC cohorts to exploit new prognostic biomarkers and further build a PRG-related signature for predicting the outcome of CC samples. Our results provided data revealing the potential functional and prognostic capabilities of the signature in Previous studies have reported PEG3 plays a central part in p53 regulated cell death, suggesting it may serve as a potential tumor suppressor.…”

Section: Discussionmentioning

confidence: 99%

“…Biomarkers can be used as indicators of pathogenesis or response to therapeutic intervention. With the advancement of genomics, a growing number of genetic markers have been uncovered, and these biomarkers have dramatically contributed to cancer research in terms of diagnosis, treatment and prognosis assessment 18–20 …”

Section: Discussionmentioning

confidence: 99%

Cross‐talk of pyroptosis‐based subtypes, the development of a risk classifier and immune responses in cervical cancer

Ding

2023

The Journal of Gene Medicine

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BackgroundCervical cancer (CC) is one of the most common gynecology malignancies and has a dismal survival outcome. The prognostic value of pyroptosis and its role in the regulation of immune metabolism in CC remain unclear.MethodsTwo independent CC cohorts collected from public databases were integrated for unsupervised cluster analysis. All CC cases were assigned to different subsets based on the pyroptosis‐related genes (PRGs). The differentially expressed genes (DEGs) between different subclusters were included in stepwise Cox regression for the risk classifier establishment. Next, single‐cell sequencing analysis was conducted to explore the cellular location of each model gene. The CIBERSORT algorithm was applied to estimate immunocytes infiltration. Finally, a series of functional experiments were performed to detect the role of CDH3 in CC.ResultsBased on the 52 PRGs, the combined CC cohort was clustered into two subsets (C1 (n = 259) and C2 (n = 242)). Survival and Cox regression methods were used to create a pyroptosis‐based risk classifier including four PRGs (PEG3, FSCN1, CDH3 and SLC2A1). For the immune environment in CC, the high‐risk group had a lower infiltration level of B cells, memory‐activated CD4 T cells and CD8 T cells and a higher infiltration abundance of neutrophils. The expression pattern of model genes was confirmed in CC cell lines by PCR assay. Furthermore, we observed that knockdown of CDH3 could suppress CC cell proliferation.ConclusionOur project could offer promising reference for prognosis assessment, immune metabolism prediction and clinical decision‐making of patients with CC.

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“…Cholesterol is a major lipid component of cell membrane and lipoproteins. Cholesterol metabolism provides the prognostic signature for HCC ( 33 ). There is a functional crosstalk in hepatocarcinogenesis between cholesterol biosynthesis and de novo lipogenesis, sharing the same precursor of acetyl-CoA ( 34 , 35 ).…”

Section: Discussionmentioning

confidence: 99%

Dual-tracer positron emission tomography/computed tomography as an imaging probe of de novo lipogenesis in preclinical models of hepatocellular carcinoma

Tsao

Jhou²,

Ke³

et al. 2022

Front. Med.

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BackgroundDe novo lipogenesis is upregulated in many cancers, and targeting it represents a metabolic approach to cancer treatment. However, the treatment response is unpredictable because lipogenic activity varies greatly among individual tumors, thereby necessitating the assessment of lipogenic activity before treatment. Here, we proposed an imaging probe, positron emission tomography/computed tomography (PET/CT) with dual tracers combining 11C-acetate and 18F-fluorodeoxyglucose (18F-FDG), to assess the lipogenic activity of hepatocellular carcinoma (HCC) and predict the response to lipogenesis-targeted therapy.MethodsWe investigated the association between 11C-acetate/18F-FDG uptake and de novo lipogenesis in three HCC cell lines (from well-differentiated to poorly differentiated: HepG2, Hep3B, and SkHep1) by examining the expression of lipogenic enzymes: acetyl-CoA synthetase 2 (ACSS2), fatty acid synthase (FASN), and ATP citrate lyase (ACLY). The glycolysis level was determined through glycolytic enzymes: pyruvate dehydrogenase expression (PDH). On the basis of the findings of dual-tracer PET/CT, we evaluated the treatment response to a lipase inhibitor (orlistat) in cell culture experiments and xenograft mice.ResultsDual-tracer PET/CT revealed the lipogenic activity of various HCC cells, which was positively associated with 11C-acetate uptake and negatively associated with 18F-FDG uptake. This finding represents the negative association between 11C-acetate and 18F-FDG uptake. Because these two tracers revealed the lipogenic and glycolytic activity, respectively, which implies an antagonism between lipogenic metabolism and glucose metabolism in HCC. In addition, dual-tracer PET/CT not only revealed the lipogenic activity but also predicted the treatment response to lipogenesis-targeted therapy. For example, HepG2 xenografts with high 11C-acetate but low 18F-FDG uptake exhibited high lipogenic activity and responded well to orlistat treatment, whereas SkHep1 xenografts with low 11C-acetate but high 18F-FDG uptake exhibited lower lipogenic activity and poor response to orlistat.ConclusionThe proposed non-invasive dual-tracer PET/CT imaging can reveal the lipogenesis and glycolysis status of HCC, thus providing an ideal imaging probe for predicting the therapeutic response of HCC to lipogenesis-targeted therapy.

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Establishment and validation of a cholesterol metabolism-related prognostic signature for hepatocellular carcinoma

Cited by 22 publications

References 63 publications

A T-cell-related signature for prognostic stratification and immunotherapy response in hepatocellular carcinoma based on transcriptomics and single-cell sequencing

A T-cell-related signature for prognostic stratification and immunotherapy response in hepatocellular carcinoma based on transcriptomics and single-cell sequencing

Cross‐talk of pyroptosis‐based subtypes, the development of a risk classifier and immune responses in cervical cancer

Dual-tracer positron emission tomography/computed tomography as an imaging probe of de novo lipogenesis in preclinical models of hepatocellular carcinoma

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