Identification of an autophagy-related gene signature predicting overall survival for hepatocellular carcinoma

Xu, Wenfang; Guo, Wenxiu; Lü, Ping; Ma, Ding; Liu, Lei; Yu, Fudong

doi:10.1042/bsr20203231

Cited by 6 publications

(5 citation statements)

References 44 publications

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“…In order to maintain the stability of the intracellular environment, autophagy involves degradation of damaged organelles or expired proteins to provide additional energy [23] [24]. Although autophagy is a normal physiological lysosome-dependent cellular self-degradation process [25], overactive autophagy may promote secondary cell death[26], as well as lead to excessive protein degradation and autophagic cell death [ 27 ] . According to previous studies[28] [29], ischemia can upregulate the autophagy activity in motor neurons, which might result in neuronal death after SCI.…”

Section: Discussionmentioning

confidence: 99%

Enolase inhibition reduces autophagy and promotes neurological function recovery after spinal cord injury

Zhou¹,

Yang

et al. 2022

Preprint

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Spinal cord injury (SCI) is a highly debilitating condition that impairs neuronal function and triggers a complex cascade of primary and secondary damage events. Autophagy can result in cell death, which is a phenomenon in eukaryotic cells and plays an important role in the development of SCI. Thus, this provides a practical and potential target for therapeutic intervention against SCI. Enolase inhibition (ENOblock) has been demonstrated to provide neuroprotection and functional recovery in a rat model of SCI. However, it remains unclear whether ENOblock can mediate neuronal autophagy after SCI. For rat model of SCI, All rats underwent laminectomy from T8 to T10. Sci rats were subjected to dorsal spinal cord exposure and SCI was injured using a modified Allen’s weight-drop apparatus. Locomotor function was assessed using the Basso, Beattie, and Bresnahan(BBB) rating scores. Thereafter we investigated the expression levels of autophagy-related proteins and Enolase by by western blot, immunofluorescence and quantitative polymerase chain reaction analysis. We found that the expression levels of autophagy-related proteins (LC3-Ⅱ and Beclin-1) and Enolase were significantly increased after acute SCI. In contrast, ENOblock could down-regulate the expression of these proteins and improve motor function after SCI. The difference between the SCI group and ENOblock group was most pronounced on the third and seventh day. Based on the above mentioned data, we speculate that ENOblock may play a role in inhibiting autophagy activity and promoting functional recovery after SCI in rats.

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Section: Discussionmentioning

confidence: 99%

Enolase inhibition reduces autophagy and promotes neurological function recovery after spinal cord injury

Zhou¹,

Yang

et al. 2022

Preprint

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“…To date, several studies have revealed the role of gene signature in predicting survival outcomes of HCC. Specifically, Wang et al ( 2020 ) identified a five immune-related gene signature, Liu et al ( 2020 ) developed a four-gene metabolic signature, and Xu et al ( 2021 ) generated an eight autophagy-related gene signature. However, our eight-HRG signature had a higher AUC in survival prediction than the above three gene signatures.…”

Section: Discussionmentioning

confidence: 99%

Novel Hypoxia-Related Gene Signature for Risk Stratification and Prognosis in Hepatocellular Carcinoma

Jin

2021

Front. Genet.

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Hepatocellular carcinoma (HCC) is the most common form of liver cancer with limited therapeutic options and low survival rate. The hypoxic microenvironment plays a vital role in progression, metabolism, and prognosis of malignancies. Therefore, this study aims to develop and validate a hypoxia gene signature for risk stratification and prognosis prediction of HCC patients. The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases were used as a training cohort, and one Gene Expression Omnibus database (GSE14520) was served as an external validation cohort. Our results showed that eight hypoxia-related genes (HRGs) were identified by the least absolute shrinkage and selection operator analysis to develop the hypoxia gene signature and demarcated HCC patients into the high- and low-risk groups. In TCGA, ICGC, and GSE14520 datasets, patients in the high-risk group had worse overall survival outcomes than those in the low-risk group (all log-rank P < 0.001). Besides, the risk score derived from the hypoxia gene signature could serve as an independent prognostic factor for HCC patients in the three independent datasets. Finally, a nomogram including the gene signature and tumor-node-metastasis stage was constructed to serve clinical practice. In the present study, a novel hypoxia signature risk model could reflect individual risk classification and provide therapeutic targets for patients with HCC. The prognostic nomogram may help predict individualized survival.

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“…1 Hepatocellular carcinoma (HCC) accounts for 85% of cases of primary liver cancer. 2 Serum alpha-fetoprotein (AFP) is recommended as an HCC-specific biomarker and is widely used in diagnosis and prognosis in HCC. 3,4 The positive rate of AFP is 41%-65% in patients with HCC, 5 and it is commonly assumed that serum AFP level has no diagnostic or prognostic role in AFP-negative HCC patients.…”

Section: Introductionmentioning

confidence: 99%

The Prognostic Value of Alpha-Fetoprotein Ratio in Patients With Resectable Alpha-Fetoprotein-Negative Hepatocellular Carcinoma

Sun,

Cen,

Zeng

et al. 2024

The American Surgeon™

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Purpose This study aimed to investigate the prognostic value of alpha-fetoprotein (AFP) ratio in patients with AFP-negative hepatocellular carcinoma (HCC). Patients and Methods We retrospectively analyzed 600 AFP-negative HCC patients who underwent hepatectomy. The AFP ratio was calculated as the ratio of AFP level 1 week before surgery to the level 20-40 days after hepatectomy. Immunohistochemistry assay was used to assess protein expression in HCC tissue. The primary outcome measures were overall survival (OS) and disease-free survival (DFS). Results The study found that a cutoff value of 1.6 ng/ml for AFP ratio, determined using X-tile software, was optimal for predicting prognosis. Patients with a high AFP ratio had a worse prognosis compare to those with a low AFP ratio (DFS, P = .026; OS, P = .034). Patients with a high AFP ratio had a worse prognosis compared to those with a low AFP ratio. Multivariate analysis revealed that AFP ratio >1.6, negative HepPar-1 expression, and vascular invasion were independent predictors of both DFS and OS. Vascular invasion had a higher area under the curve (AUC) than AFP ratio and HepPar-1 expression in predicting recurrence and death. The combination of AFP ratio, HepPar-1 expression, and vascular invasion provided better predictive accuracy for DFS and OS. Conclusion The AFP ratio is a potential prognostic marker for AFP-negative HCC patients after hepatectomy. Combining the analysis of AFP ratio with HepPar-1 expression and vascular invasion can enhance the accuracy of predicting prognosis in these patients.

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Identification of an autophagy-related gene signature predicting overall survival for hepatocellular carcinoma

Cited by 6 publications

References 44 publications

Enolase inhibition reduces autophagy and promotes neurological function recovery after spinal cord injury

Enolase inhibition reduces autophagy and promotes neurological function recovery after spinal cord injury

Novel Hypoxia-Related Gene Signature for Risk Stratification and Prognosis in Hepatocellular Carcinoma

The Prognostic Value of Alpha-Fetoprotein Ratio in Patients With Resectable Alpha-Fetoprotein-Negative Hepatocellular Carcinoma

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