A distinctively expressed long noncoding RNA, RP11-466I1.1, may serve as a prognostic biomarker in hepatocellular carcinoma.

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It is urgent to explore effective diagnostic and prognostic biomarkers for hepatocellular carcinoma (HCC). Now, both lncRNAs and lipid metabolism are involved in tumor pathogenesis. Long noncoding RNA, RP11‐466I1.1, could likely be linked to lipid metabolism according to our bioinformatics analysis, yet studies about RP11‐466I1.1 expression in tumors and its potential functions are still lacking. We aimed to explore the expression and correlations with clinical features of a long noncoding RNA, RP11‐466I1.1, and further analyze its diagnostic and prognostic values in hepatocellular carcinoma. Expression levels of RP11‐466I1.1 were detected by quantitative real‐time PCR (qRT‐PCR) in tissue and serum level, and expression differences were analyzed by independent 2‐tailed t tests. Clinical features were obtained, and their correlations with RP11‐466I1.1 were analyzed by chi‐squared test. Receiver operating characteristic (ROC) curve was performed to assess the diagnostic value. Kaplan‐Meier method and log‐rank test were used to evaluate the prognostic value of RP11‐466I1.1. Results showed that RP11‐466I1.1 was upregulated in HCC tissues (P < .01) and serum (P < .05). Significant upregulation of RP11‐466I1.1 in HCC tissues with poor histological grade (P < .01) and incomplete tumor capsule (P < .01) was found compared to that with better histological grade and complete tumor capsule, respectively. The diagnostic value of RP11‐466I1.1 was not supported by ROC curve analysis (AUROC=0.665, P = .079). Yet, the significant correlation of RP11‐466I1.1 with poor prognosis indicated its potential prognostic value in HCC. This study suggested that RP11‐466I1.1 is distinctively expressed in HCC and may serve as a promising novel prognostic biomarker. The concrete mechanisms of RP11‐466I1.1 playing roles in HCC pathogenesis need further study.

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BackgroundCytokeratin 19 (CK19), Ki67 antigen (Ki67), and β-catenin are abnormally overexpressed in hepatocellular carcinoma (HCC), but their diagnostic and prognostic value remains unclear. This study aims to investigate the predictive role of these three markers in post-operative survival of HCC patients.MethodsThe expression levels of CK19, Ki67, and β-catenin in HCC tumor tissues were determined through public datasets. Kaplan-Meier survival analysis and multivariate Cox regression were performed to evaluate their prognostic value. Immunohistochemistry and Western blotting were used to detect the expression levels of CK19, Ki67, and β-catenin in hepatocellular carcinoma tissues and adjacent non-cancerous tissues. Transcriptome sequencing was performed to analyze the differential transcriptional changes between HCC and adjacent non-cancerous tissues. A cohort of HCC post-operative patients was included to analyze the correlation between the three markers and clinical pathological features.ResultsCK19, Ki67, and β-catenin were highly expressed in HCC tissues and lowly expressed in adjacent non-cancerous tissues. High expression of CK19, Ki67, and β-catenin was closely associated with poor disease-free survival (DFS) and overall survival (OS) in HCC patients’ post-surgery. These three markers serve as independent prognostic factors for DFS and OS. Immunohistochemistry and Western blotting revealed upregulation of CK19, Ki67, and β-catenin in HCC tissues, while transcriptome sequencing indicated alterations related to metabolic reprogramming, immune evasion, and invasion/metastasis in HCC. Clinical data from HCC patients showed that CK19 expression correlated with tumor number and differentiation grade, Ki67 expression correlated with patient age, tumor size, tumor number, lymphatic metastasis, and tumor differentiation, while β-catenin expression was closely related to tumor diameter, number, and capsule status.ConclusionCK19, Ki67, and β-catenin are highly expressed in HCC and can serve as molecular markers for post-operative recurrence and poor survival in HCC patients, providing a basis for precise prognostic evaluation in HCC.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12885-025-15429-6.

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Diagnostic and prognostic values of upregulated SPC25 in patients with hepatocellular carcinoma.
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Identification and validation of EPHX2 as a prognostic biomarker in hepatocellular carcinoma.
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Integrative Analysis of Metallothioneins Identifies MT1H as Candidate Prognostic Biomarker in Hepatocellular Carcinoma.
  • Oct 5, 2021
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  • Feng Zhang + 4 more

Background: Metallothioneins (MTs) play crucial roles in the modulation of zinc/copper homeostasis, regulation of neoplastic growth and proliferation, and protection against apoptosis. The present study attempted to visualize the prognostic landscape of MT functional isoforms and identify potential prognostic biomarkers in hepatocellular carcinoma (HCC). Methods: The transcriptional expression, comprehensive prognostic performances, and gene–gene interaction network of MT isoforms in HCC were evaluated via Oncomine, GEPIA, Kaplan–Meier plotter, and GeneMANIA databases. Characterized by good prognostic value in three external cohorts, MT1H was specifically selected as a potential prognostic biomarker in HCC with various clinicopathological features. Functional and pathway enrichment analyses of MT1H status were performed using cBioPortal, the Database for Annotation, Visualization, and Integrated Discovery (DAVID), and ssGSVA method. Results: MT1E/1F/1G/1H/1M/1X/2A was greatly downregulated in HCC. Prognostic analyses elucidated the essential correlations between MT1A/1B/1H/1X/2A/4 attenuation and poor overall survival, between MT1B/1H/4 downregulation and worse relapse-free survival, and between MT1A/1B/1E/1H/1M/2A/4 downregulation and diminished progression-free survival in HCC. Taken together, these results indicated the powerful prognostic value of MT1H among MTs in HCC. In-depth analyses suggested that MT1H may be more applicable to alcohol-derived HCC and involved in the downregulation of the inflammatory pathway, Jak–STAT pathway, TNF pathway, and Wnt signaling pathway. Conclusion: MT-specific isoforms displayed aberrant expression and varying prognostic value in HCC. MT1H repression in HCC was multi-dimensionally detrimental to patient outcomes. Therefore, MT1H was possibly associated with carcinogenesis and exploited as a novel prognostic biomarker and candidate therapeutic target for HCC.

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Identification of long noncoding RNAs biomarkers in patients with hepatitis B virus-associated hepatocellular carcinoma.
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  • Cite Count Icon 106
  • 10.3390/jcm9010281
Serum Exosomal MicroRNA, miR-10b-5p, as a Potential Diagnostic Biomarker for Early-Stage Hepatocellular Carcinoma
  • Jan 20, 2020
  • Journal of Clinical Medicine
  • Hyo Jung Cho + 7 more

Exosomal microRNAs (exo-miRs) have been promising cancer biomarkers. MiRs in hepatocellular carcinoma (HCC) cell-derived exosomes (HEX) were analyzed to identify reliable serum biomarkers for HCC. To detect overexpressed miRs in HEX, extracted exosomal small RNAs from human HCC cell lines and normal hepatocytes were sequenced and analyzed. Clinical significance of the overexpressed miRs in HEX was evaluated using quantitative real-time PCR (qRT-PCR) on serum samples of a validation cohort consisting of 28 healthy individuals, 60 with chronic liver disease, and 90 with HCC. We found 49 significantly overexpressed miRs in HEX compared to a normal hepatocyte. Among them, miR-10b-5p, miR-18a-5p, miR-215-5p, and miR-940 were overexpressed in HCC tissues and also associated with prognosis of HCC in the analysis of a public omics database. qRT-PCR analysis of the four serum exo-miRs in the validation cohort revealed serum exo-miR-10b-5p as a promising biomarker for early-stage HCC with 0.934 area under the curve (AUC) (sensitivity, 90.7%; specificity, 75.0%; cutoff value, 1.8-fold). Overexpression of serum exo-miR-215-5p was found to be significantly associated with poor disease-free survival in patients with HCC. Serum exo-miR-10b-5p is a potential biomarker for early-stage HCC, while serum exo-miR-215-5p can be used as prognostic biomarker for HCC.

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