Tescalcin is an unfavorable prognosis factor that regulats cell proliferation and survival in hepatocellular carcinoma patients

Zhou, Zhongguo; Chen, Jinbin; Zhang, Rong‐Xin; Ye, Ling; Wang, Juncheng; Pan, Yangxun; Wang, Xiaohui; Li, Wen‐Xuan; Zhang, Yaojun; Xu, Li; Chen, Minshan

doi:10.1002/cac2.12069

Cited by 16 publications

(13 citation statements)

References 44 publications

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“…One of the network-common lncRNAs, Meg3 (lnc10922*), inhibits HSC activation and accelerates the reversal of CCl 4 -induced fibrosis 113 . Network-essential PCG regulators common to both networks include: Ifnar2, which mediates many anti-viral immune responses and has a gene polymorphism linked to hepatocellular carcinoma 114 ; Ets1, which regulates HSC activation in NASH liver and is a profibrogenic marker in CCl 4 -induced fibrosis 115 , where it is a critical mediator of extracellular matrix remodeling 116 ; Tesc, which had the highest PageRank centrality score in the CCl 4 network and negatively regulates cell proliferation and survival in hepatocellular carcinoma 117 ; and Nr1h4 (FXR), which regulates lipid and glucose homeostasis and is involved innate immune responses 118 .…”

Section: Resultsmentioning

confidence: 99%

Dysregulation of murine long non-coding single cell transcriptome in non-alcoholic steatohepatitis and liver fibrosis

Karri

Waxman

2022

Preprint

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LncRNAs are typified by low expression, nuclear enrichment, high tissue-specificity and functional diversity, but the vast majority are uncharacterized. Here, we develop a catalog of 48,000 mouse liver-expressed lncRNAs and use to elucidate lncRNA dysregulation in high fat diet-induced non-alcoholic steatohepatitis and carbon tetrachloride-induced liver fibrosis by single cell RNA-seq. LncRNA zonation patterns across the liver lobule were discovered in five cell populations. Perturbations in lncRNA expression were common in disease-associated cell types, including non-alcoholic steatohepatitis-associated macrophages, a hallmark of fatty liver disease progression, and collagen-producing myofibroblasts, key to liver fibrosis. Gene regulatory network analysis linked individual lncRNAs to biological pathways and network centrality metrics identified network-essential, disease-associated regulatory lncRNAs. Regulatory lncRNAs with network-predicted target gene promoters enriched for triplex-based lncRNA binding were also identified. These findings elucidate hepatic lncRNA cell-type specificities, spatial zonation patterns, linked biological networks and dysregulation in disease progression. A subset of the disease-associated lncRNAs have human orthologs and are promising candidates for biomarkers and therapeutic targets.

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Section: Resultsmentioning

confidence: 99%

Dysregulation of murine long non-coding single cell transcriptome in non-alcoholic steatohepatitis and liver fibrosis

Karri

Waxman

2022

Preprint

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“…And it was commonly recognized that the development of CRC accumulated a series of mutations to gain metastatic competence, including the ability to proliferate, invade into the surrounding tissues, survive in the circulatory system, colonize distant organs and eventually resume growth (14). Several oncogenes including the Kras with Apc and Tp53 deficiency were sufficient to enhance proliferation in animal experiment (15,16). It was commonly accepted that cancer cells dysregulation in various pathological conditions, and it had been proven to be a critical role in various malignancies (18)(19)(20).…”

Section: Discussionmentioning

confidence: 99%

The apolipoprotein B and apolipoprotein A-I Ratio serves as a strong prognostic factor for the overall survival of patients with colorectal cancer

Pan

Ling

et al. 2023

Front. Oncol.

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BackgroundThe lipid metabolism status of patients with colorectal cancer (CRC) has not been understood comprehensively. The present study investigated the characteristics of lipid metabolism parameters in CRC patients with or without metastases and identified the independent prognostic factors of long-term prognosis.MethodsThe clinicopathological data of 231 CRC patients along with 259 formalin-fixed paraffin-embedded samples with or without liver or lung metastasis were retrieved and stained for apolipoprotein B (apoB) via immunohistochemistry (IHC) in our center. The correlation and multivariable analysis between blood circulating apolipoprotein A-I (apoA1), apoB and overall survival (OS) were analyzed.ResultsIn the multivariable analysis, apoA1, apoB and apolipoprotein B and apolipoprotein A-I (apoB/A) ratio, were identified as independent prognostic factors for OS. Moreover, the apoB/A ratio showed a significantly negative association with OS time (R=-0.187, P=0.004). CRC patients with low apoB/A ratio had better 1-, 3- and 5-year OS rates than those who had high apoB/A ratio (87.1%, 54.3%, and 37.1% vs. 92.5%, 72.0%, and 59.5%, respectively, P=0.001). On histological level, similar expression intensity of apoB between primary CRC and liver metastases indicated better prognostic outcomes than those with different expression levels (100%, 83.3%, and 77.8% vs. 100%, 66.7%, and 33.3%, respectively; P=0.033). Higher level of apoB in the primary CRC interprets into increased incidence of liver metastases. However, the apoB expression levels in the CRC tumor were not parallel to the circulating lipid metabolism parameters.ConclusionsThe apoB/A ratio was a reliable independent prognostic factor for predicting the long-term OS of CRC patients. Moreover, the IHC of the primary CRC and metastatic lesions verified the metastatic potential of apoB through a different aspect. Lipid metabolism status for cancer progression reported in the present study possessed potentially prognostic value, but bench-scale studies are needed for their future clinical applications.

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“…Although the introduction of ICIs into the HCC treatment has improved the survival of patients in recent years, the response rates of ICIs were still limited because of the variable immune conditions of patients ( Zhou ZG et al, 2020 ; Schoenfeld and Hellmann, 2020 ; Pan et al, 2021 ). Unfortunately, there is no biological marker available in predicting the responses to ICIs regarding HCC.…”

Section: Discussionmentioning

confidence: 99%

Development and Validation of a Prognostic Score for Hepatocellular Carcinoma Patients in Immune Checkpoint Inhibitors Therapies: The Hepatocellular Carcinoma Modified Gustave Roussy Immune Score

Pan

Lin

et al. 2022

Front. Pharmacol.

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Background: There is not yet an effective marker in predicting the efficacy of immune checkpoint inhibitors (ICIs) in treating hepatocellular carcinoma (HCC) patients. The Gustave Roussy Immune Score (GRIm-Score) based on three objective variables, namely, neutrophil-to-lymphocyte ratio (NLR), serum albumin level (ALB), and lactate dehydrogenase (LDH), was developed as feasible prognostic indication in lung cancer patients receiving ICIs therapies. Our study aimed to adapt the GRIm-Score (HCC-GRIm-Score) in HCC patients who received ICIs therapies and thus improving the predictive ability.Methods: From January 2018 to September 2020, 261 patients who received ICIs therapy were retrospectively included and divided into training and validation groups. After determining the factors for HCC-GRIm-Score by multivariable analysis from training group, the optimized HCC-GRIm-Score was validated and compared to the original GRIm-Score and the Barcelona clinic liver cancer (BCLC) staging system.Results: One hundred sixty-one and 80 patients were assigned into the training and validation groups, respectively. Two more factors, aspartate transaminase-to-alanine transaminase ratio [hazard ratio (HR), 1.51; 95% confidence interval (CI), 0.94–2.42] and total bilirubin (HR, 1.76; 95% CI, 1.07–2.88), were identified as independent prognostic factors for overall survival (OS) and integrated in the HCC-GRIm-Score system according to the multivariable analysis. A risk score based on the HCC-GRIm-Score indicated that patients presenting high score (>2) suffered from significantly shorter median OS of 10.3 months compared to those with a low score (not reached; HR, 2.99; 95% CI, 1.89–4.75; p < 0.001). In the validation group of 80 patients, the patients presenting a high score showed an inferior OS (HR 5.62, 95% CI, 1.25–25.24; p = 0.024). HCC-GRIm-Score had the highest area under curve of 0.719 (95% CI, 0.661–0.773) compared to original GRIm-Score and BCLC staging system.Conclusion: The present study confirmed that the modified HCC-GRIm-Score system provided superior predictive ability in identifying the HCC patients potentially benefit from ICIs therapies, compared to the original GRIm-Score and the BCLC staging system.

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Tescalcin is an unfavorable prognosis factor that regulats cell proliferation and survival in hepatocellular carcinoma patients

Cited by 16 publications

References 44 publications

Dysregulation of murine long non-coding single cell transcriptome in non-alcoholic steatohepatitis and liver fibrosis

Dysregulation of murine long non-coding single cell transcriptome in non-alcoholic steatohepatitis and liver fibrosis

The apolipoprotein B and apolipoprotein A-I Ratio serves as a strong prognostic factor for the overall survival of patients with colorectal cancer

Development and Validation of a Prognostic Score for Hepatocellular Carcinoma Patients in Immune Checkpoint Inhibitors Therapies: The Hepatocellular Carcinoma Modified Gustave Roussy Immune Score

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