Association of Postoperative Biomarker Response with Recurrence and Survival in Patients with Hepatocellular Carcinoma and High Alpha-Fetoprotein Expressions (&gt;400 ng/ml)

Liang, Lei; Wang, Mingda; Zhang, Yaoming; Zhang, Wanguang; Zhang, Chengwu; Lau, Wan Yee; Shen, Feng; Pawlik, Timothy M.; Huang, Dongsheng; Yang, Tian

doi:10.2147/jhc.s289840

Cited by 13 publications

(8 citation statements)

References 56 publications

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“…The survival analysis in this cohort also showed that patients with high AUF1 expression had a worse prognosis, although the difference was not statistically significant ( P = .059; Figure 1F). It is well known that elevated Alpha fetoprotein (AFP) levels are associated with the poor prognosis of patients with HCC 22 . In line with this, the AUF1 expression levels in patients with serum AFP levels ≥300 ng/mL were significantly higher than for patients with serum AFP levels <300 ng/mL in both the LCI ( P < .001; Figure C) and TCGA databases ( P < .001; Figure D).…”

Section: Resultssupporting

confidence: 72%

“…It is well known that elevated Alpha fetoprotein (AFP) levels are associated with the poor prognosis of patients with HCC. 22 In line with this, the AUF1 expression levels in patients with serum AFP levels ≥300 ng/ mL were significantly higher than for patients with serum AFP levels <300 ng/mL in both the LCI (P < .001; Figure S1C) and TCGA databases (P < .001; Figure S1D). Additionally, the expression levels of AUF1 mRNA were significantly higher in the tumor tissues derived from patients with HCC who had Barcelona Clinic Liver Cancer (BCLC) stage C or larger tumors than that from patients who had BCLC stage A (P = .011; Figure S1E) or smaller tumors (P = .047;…”

Section: Auf1 Is Highly Expressed In Hcc and Predicts Poor Prognosissupporting

confidence: 73%

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E2F1‐mediated AUF1 upregulation promotes HCC development and enhances drug resistance via stabilization of AKR1B10

et al. 2022

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The AU-rich binding factor 1 (AUF1) is one of the well known adenylate-uridylate-rich element (ARE)-specific RNA-binding proteins (ARE-BPs) for which dysregulation has been reported in various human cancers. However, the involvement of AUF1 in the initiation and progression of hepatocellular carcinoma (HCC) is still elusive. In this study, we aimed at exploring the clinical significance, function, and mechanism of the abnormal expression of AUF1 in HCC. Using a bioinformatics analysis of The Cancer Genome Atlas (TCGA) and Liver Cancer Institute (LCI) database, we identified that AUF1 was abnormally highly expressed in HCC tissues and that the high expression of AUF1 was correlated with poor prognosis in patients with HCC. We also confirmed the increased AUF1 expression and its prognostic value in our HBV-related HCC cohorts. AUF1 overexpression in hepatoma cells promoted cell proliferation and increased the resistance of hepatoma cells toward doxorubicin, whereas knockdown of AUF1 exerted the opposite effects. Mechanistically, we demonstrated that AKR1B10 was a critical target of AUF1 and was essential for sustaining the AUF1-induced proliferation and drug resistance of hepatoma cells. AUF1 increased AKR1B10 expression by binding to the 3′UTR region of AKR1B10 mRNA and stabilizing AKR1B10 mRNA.Additionally, we demonstrated that E2F1 enhanced AUF1 expression in HCC at the transcription level. Our study revealed a novel role of AUF1 in promoting the development and drug resistance of HCC via the post-transcriptional regulation of AKR1B10 expression. The E2F1/AUF1/AKR1B10 axis can serve as a potential therapeutic target in HCC.

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Section: Resultssupporting

confidence: 72%

Section: Auf1 Is Highly Expressed In Hcc and Predicts Poor Prognosissupporting

confidence: 73%

E2F1‐mediated AUF1 upregulation promotes HCC development and enhances drug resistance via stabilization of AKR1B10

et al. 2022

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“…A large number of studies showed that tumor size and AFP were crucial prognostic factors of HCC. [18][19][20] The similar result was also observed in this present study. When combined with tumor size and AFP, the AIAG (0.705, 95% CI: 0.655-0.755) indicated a higher rank than BCLC staging system (Table 4).…”

Section: Comparing the Accuracy Of Predicting Survival Between The Aiag And The Classic Bclc Stagesupporting

confidence: 92%

The Combination of Age, International Standardized Ratio, Albumin and γ-Glutamyl Transpeptidase (AIAG), Tumor Size and Alpha Fetoprotein (AFP) Stage as the Prognostic Model for Hepatitis B-Related Hepatocellular Carcinoma

Liu

Fang

et al. 2021

IJGM

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Background Advanced liver fibrosis can lead to cirrhosis, portal hypertension and liver failure. Besides, advanced liver fibrosis and cirrhosis are the major risk factors for hepatocellular carcinoma (HCC). Almost all patients with HCC also have liver cirrhosis. This study aims to predict the survival rate of hepatitis B-related hepatocellular carcinoma (HCC) by age, international standardized ratio, albumin and γ-glutamyl transpeptidase (AIAG), an indicator measuring the degree of cirrhosis. Methods A total of 501 hepatitis B-related HCC patients experiencing radical surgery were analyzed, retrospectively. General data about demographics and labs were collected at the date of diagnosis to calculate AIAG [age, international standardized ratio (INR), albumin and gamma-glutamyl transferase (GGT)]. The Kaplan–Meier curves and Cox analysis were used to evaluate overall survival (OS) and recurrence-free survival (RFS). The C-index was calculated in R software (version 4.0.3) to evaluate the accuracy of the prognostic model. Results During a median follow-up period of 30 months, 31.1% (156/501) of the patients died, and 34.3% (172/501) experienced the recurrence of HCC. Compared with patients with lower AIAG score, patients with higher AIAG score had higher Child-Pugh grade and were at higher Barcelona Clinic Liver Cancer (BCLC) stage (both P <0.05). Multivariate analysis suggested that GGT, alpha fetoprotein (AFP), tumor size, BCLC stage and AIAG grade were independent predictors of OS and RFS. Furthermore, the combined use of tumor size, AFP and AIAG stage could predict survival significantly better (C-index=0.710, 95% CI: 0.669–0.751) than BCLC stage. Conclusion AIAG is significantly associated with survival of HCC patients, and provides additional prognostic information for patients with HCC. Our findings suggest that the combination of AIAG, tumor size and AFP stage has a better predictive value for the prognosis of patients with hepatitis B-related hepatocellular carcinoma. However, it is necessary for more external evidences to determine clinical utility.

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“…Sixty-five patients with HCC were divided into two groups based on their preoperative serum AFP levels. We set AFP > 400 ng/ml as the cut-off criterion, as it is considered to be associated with adverse outcomes and oncological characteristics of HCC [ 29 ]. There were 22 cases in the AFP-high group (serum AFP > 400 ng/ml) and 43 in the AFP-low group (serum AFP ≤ 400 ng/ml).…”

Section: Resultsmentioning

confidence: 99%

Whole‐Transcriptome Sequencing Combined with High‐Dimensional Proteomic Technologies Reveals the Potential Value of miR‐135b‐5p as a Biomarker for Hepatocellular Carcinoma

Zhang

Pan

et al. 2023

BioMed Research International

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Purpose. Hepatocellular carcinoma (HCC) is a disease with great heterogeneity and a high mortality rate. It is crucial to identify reliable biomarkers for diagnosis, prognosis, and treatment to improve clinical outcomes in patients with HCC. Alpha-fetoprotein (AFP) is not only a widely used biomarker in clinical practice but also plays a complicated role in HCC, and it has recently been considered to be related to immunotherapy. MicroRNAs (miRNAs) are regarded as key regulators and promising biomarkers of HCC. We investigated the role of an AFP-related miRNA, miR-135b-5p, in HCC progression. Methods. Identification of miR-135b-5p was performed based on a cohort of 65 HCC cases and the liver hepatocellular carcinoma cohort of The Cancer Genome Atlas (Asian people only). A combination of whole-transcriptome sequencing and high-dimensional proteomic technologies was used to study the role of miR-135b-5p in HCC. Results. Upregulation of miR-135b-5p was detected in patients with HCC with high serum AFP levels ( AFP > 400 ng / ml ). Elevated miR-135b-5p expression was associated with adverse prognosis. We also identified the relevance between high miR-135b-5p expression and tumor-related pathological characteristics, such as Edmondson grade and vascular invasion. We revealed tyrosine kinase nonreceptor 1 as a potential target of miR-135b-5p. Additionally, the transcriptional start site of miR-135b-5p had potential binding sites for SRY-box transcription factor 9, and the stemness properties of tumor cells were more remarkable in HCC with the upregulation of miR-135b-5p. The molecular characterization of the miR-135b-5p-high group was similar to that of the HCC subclasses containing moderately and poorly differentiated tumors. Finally, gene signatures associated with improved clinical outcomes in immune checkpoint inhibitor therapy were upregulated in the miR-135b-5p-high group. Conclusion. miR-135b-5p could be a biomarker for predicting the prognosis and antiprogrammed cell death protein 1 monotherapy response in HCC.

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Association of Postoperative Biomarker Response with Recurrence and Survival in Patients with Hepatocellular Carcinoma and High Alpha-Fetoprotein Expressions (>400 ng/ml)

Cited by 13 publications

References 56 publications

E2F1‐mediated AUF1 upregulation promotes HCC development and enhances drug resistance via stabilization of AKR1B10

E2F1‐mediated AUF1 upregulation promotes HCC development and enhances drug resistance via stabilization of AKR1B10

The Combination of Age, International Standardized Ratio, Albumin and γ-Glutamyl Transpeptidase (AIAG), Tumor Size and Alpha Fetoprotein (AFP) Stage as the Prognostic Model for Hepatitis B-Related Hepatocellular Carcinoma

Whole‐Transcriptome Sequencing Combined with High‐Dimensional Proteomic Technologies Reveals the Potential Value of miR‐135b‐5p as a Biomarker for Hepatocellular Carcinoma

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