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  • 1
    Online Resource
    Online Resource
    Characteristic molecular signature of pericardial effusion identifies malignant cancer in pericardial disorder patients
    Springer Science and Business Media LLC ; 2020
    In:  Molecular & Cellular Toxicology Vol. 16, No. 3 ( 2020-07), p. 211-220
    Details
    In: Molecular & Cellular Toxicology, Springer Science and Business Media LLC, Vol. 16, No. 3 ( 2020-07), p. 211-220
    Type of Medium: Online Resource
    ISSN: 1738-642X , 2092-8467
    URL: Article
    DOI: 10.1007/s13273-020-00076-8
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2498324-X
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  • 2
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    Online Resource
    Serum Proteins, HMMR, NXPH4, PITX1 and THBS4; A Panel of Biomarkers for Early Diagnosis of Hepatocellular Carcinoma
    MDPI AG ; 2022
    In:  Journal of Clinical Medicine Vol. 11, No. 8 ( 2022-04-11), p. 2128-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 11, No. 8 ( 2022-04-11), p. 2128-
    Abstract: The high morbidity rate of hepatocellular carcinoma (HCC) is mainly linked to late diagnosis. Early diagnosis of this leading cause of mortality is therefore extremely important. We designed a gene selection strategy to identify potential secretory proteins by predicting signal peptide cleavage sites in amino acid sequences derived from transcriptome data of human multistage HCC comprising chronic hepatitis, liver cirrhosis and early and overt HCCs. The gene selection process was validated by the detection of molecules in the serum of HCC patients. From the computational approaches, 10 gene elements were suggested as potent candidate secretory markers for detecting HCC patients. ELISA testing of serum showed that hyaluronan mediated motility receptor (HMMR), neurexophilin 4 (NXPH4), paired like homeodomain 1 (PITX1) and thrombospondin 4 (THBS4) are early-stage HCC diagnostic markers with superior predictive capability in a large cohort of HCC patients. In the assessment of differential diagnostic accuracy, receiver operating characteristic curve analyses showed that HMMR and THBS4 were superior to α-fetoprotein (AFP) in diagnosing HCC, as evidenced by the high area under the curve, sensitivity, specificity, accuracy and other values. In addition, comparative analysis of all four markers and AFP combinations demonstrated that HMMR-PITX1-AFP and HMMR-NXPH4-PITX1 trios were the optimal combinations for reaching 100% accuracy in HCC diagnosis. Serum proteins HMMR, NXPH4, PITX1 and THBS4 can complement measurement of AFP in diagnosing HCC and improve identification of patients with AFP-negative HCC as well as discriminate HCC from non-malignant chronic liver disease.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm11082128
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662592-1
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  • 3
    Online Resource
    Online Resource
    Novel Gene Signatures as Prognostic Biomarkers for Predicting the Recurrence of Hepatocellular Carcinoma
    MDPI AG ; 2022
    In:  Cancers Vol. 14, No. 4 ( 2022-02-09), p. 865-
    Details
    In: Cancers, MDPI AG, Vol. 14, No. 4 ( 2022-02-09), p. 865-
    Abstract: Hepatocellular carcinoma (HCC) has a high rate of cancer recurrence (up to 70%) in patients who undergo surgical resection. We investigated prognostic gene signatures for predicting HCC recurrence using in silico gene expression analysis. Recurrence-associated gene candidates were chosen by a comparative analysis of gene expression profiles from two independent whole-transcriptome datasets in patients with HCC who underwent surgical resection. Five promising candidate genes, CETN2, HMGA1, MPZL1, RACGAP1, and SNRPB were identified, and the expression of these genes was evaluated using quantitative reverse transcription PCR in the validation set (n = 57). The genes CETN2, HMGA1, RACGAP1, and SNRPB, but not MPZL1, were upregulated in patients with recurrent HCC. In addition, the combination of HMGA1 and MPZL1 demonstrated the best area under the curve (0.807, 95% confidence interval [CI] = 0.681–0.899) for predicting HCC recurrence. In terms of clinicopathological correlation, CETN2, MPZL1, RACGAP1, and SNRPB were upregulated in patients with microvascular invasion, and the expression of MPZL1 and SNRPB was increased in proportion to the Edmonson tumor differentiation grade. Additionally, overexpression of CETN2, HMGA1, and RACGAP1 correlated with poor overall survival (OS) and disease-free survival (DFS) in the validation set. Finally, Cox regression analysis showed that the expression of serum alpha-fetoprotein and RACGAP1 significantly affected OS, whereas platelet count, microvascular invasion, and HMGA1 expression significantly affected DFS. In conclusion, HMGA1 and RACGAP1 may be potential prognostic biomarkers for predicting the recurrence of HCC after surgical resection.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers14040865
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527080-1
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  • 4
    Online Resource
    Online Resource
    Exosomal microRNA‐4661‐5p–based serum panel as a potential diagnostic biomarker for early‐stage hepatocellular carcinoma
    Wiley ; 2020
    In:  Cancer Medicine Vol. 9, No. 15 ( 2020-08), p. 5459-5472
    Details
    In: Cancer Medicine, Wiley, Vol. 9, No. 15 ( 2020-08), p. 5459-5472
    Abstract: Currently, a reliable serum biomarker for hepatocellular carcinoma (HCC) has not been established, particularly for early‐stage HCC (single tumor  〈  2 cm). We aimed to investigate diagnostic serum exosomal microRNA (exo‐miR) panel for early‐stage HCC. Driver oncogenic miR (onco‐miR) candidates were selected by integrative analysis of miR expression profiles from three different RNA sequencing datasets of human HCC. Expressions of selected onco‐miRs in serum exosome were measured using quantitative real‐time PCR. Diagnostic performances of serum exo‐miRs for HCC were evaluated in the test cohort (N = 24) and validation cohort (N = 144). Serum exo‐miR panels were developed using a logistic regression model, and their diagnostic performance was evaluated. Six promising driver onco‐miRs, including miR‐25‐3p, miR‐140‐3p, miR‐423‐3p, miR‐1269a, miR‐4661‐5p, and miR‐4746‐5p, were identified by integrative analysis of three different RNA sequencing datasets. Among the six candidates, four serum exo‐miRs (miR‐25‐3p, miR‐1269a, miR‐4661‐5p, and miR‐4746‐5p) showed promising performance in the test cohort with area under the receiving operator curve (AUROC) 〉 0.8. In our validation study, serum exo‐miR‐4661‐5p could diagnose HCC in all stages (AUROC = 0.917), even in early stage (AUROC = 0.923), with a greater accuracy than other candidate serum exo‐miRs and serum AFP. The panel composed of exo‐miR‐4661‐5p and exo‐miR‐4746‐5p was identified as the most accurate biomarker for early‐stage HCC (AUROC = 0.947, 95% confidence interval = 0.889‐0.980, sensitivity = 81.8%, and specificity = 91.7%). In conclusion, exo‐miR‐4661‐5p–based serum panel is a promising diagnostic marker for early‐stage HCC.
    Type of Medium: Online Resource
    ISSN: 2045-7634 , 2045-7634
    URL: Issue
    URL: Article
    DOI: 10.1002/cam4.v9.15
    DOI: 10.1002/cam4.3230
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2659751-2
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  • 5
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    Online Resource
    Early detection of hepatocellular carcinoma via liquid biopsy: panel of small extracellular vesicle‐derived long noncoding RNAs identified as markers
    Wiley ; 2021
    In:  Molecular Oncology Vol. 15, No. 10 ( 2021-10), p. 2715-2731
    Details
    In: Molecular Oncology, Wiley, Vol. 15, No. 10 ( 2021-10), p. 2715-2731
    Abstract: This study investigated the diagnostic potential of serum small extracellular vesicle‐derived long noncoding RNAs (EV‐lncRNAs) for hepatocellular carcinoma (HCC). Driver oncogenic lncRNA candidates were selected by a comparative analysis of lncRNA expression profiles from two whole transcriptome human HCC datasets (Catholic_LIHC and TCGA_LIHC). Expression of selected lncRNAs in serum and small EVs was evaluated using quantitative reverse transcription PCR. Diagnostic power of serum EV‐lncRNAs for HCC was determined in the test ( n  = 44) and validation ( n  = 139) cohorts. Of the six promising driver onco‐lncRNAs, DLEU2 , HOTTIP , MALAT1, and SNHG1 exhibited favorable performance in the test cohort. In the validation cohort, serum EV‐ MALAT1 displayed excellent discriminant ability, while EV‐ DLEU2 , EV ‐HOTTIP, and EV‐ SNHG1 showed good discriminant ability between HCC and non‐HCC. Furthermore, a panel combining EV‐ MALAT1 and EV‐ SNHG1 achieved the best area under the curve (AUC; 0.899, 95% CI = 0.816–0.982) for very early HCC, whereas a panel with EV‐ DLEU2 and alpha‐fetoprotein exhibited the best positivity (96%) in very early HCC. Serum small EV‐ MALAT1 , EV‐ DLEU2 , EV‐ HOTTIP, and EV‐ SNHG1 may represent promising diagnostic markers for very early‐stage HCC.
    Type of Medium: Online Resource
    ISSN: 1574-7891 , 1878-0261
    URL: Issue
    URL: Article
    DOI: 10.1002/mol2.v15.10
    DOI: 10.1002/1878-0261.13049
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2322586-5
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  • 6
    Online Resource
    Online Resource
    Nucleoporin 210 Serves a Key Scaffold for SMARCB1 in Liver Cancer
    American Association for Cancer Research (AACR) ; 2021
    In:  Cancer Research Vol. 81, No. 2 ( 2021-01-15), p. 356-370
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 81, No. 2 ( 2021-01-15), p. 356-370
    Abstract: The roles of chromatin remodelers and their underlying mechanisms of action in cancer remain unclear. In this study, SMARCB1, known initially as a bona fide tumor suppressor gene, was investigated in liver cancer. SMARCB1 was highly upregulated in patients with liver cancer and was associated with poor prognosis. Loss- and gain-of-function studies in liver cells revealed that SMARCB1 loss led to reduced cell proliferation, wound healing capacity, and tumor growth in vivo. Although upregulated SMARCB1 appeared to contribute to switch/sucrose nonfermentable (SWI/SNF) complex stability and integrity, it did not act using its known pathways antagonism with EZH2 or association between TP53 or AMPK. SMARCB1 knockdown induced a mild reduction in global H3K27 acetylation, and chromatin immunoprecipitation sequencing of SMARCB1 and acetylated histone H3K27 antibodies before and after SMARCB1 loss identified Nucleoporin210 (NUP210) as a critical target of SMARCB1, which bound its enhancer and changed H3K27Ac enrichment and downstream gene expression, particularly cholesterol homeostasis and xenobiotic metabolism. Notably, NUP210 was not only a putative tumor supporter involved in liver cancer but also acted as a key scaffold for SMARCB1 and P300 to chromatin. Furthermore, SMARCB1 deficiency conferred sensitivity to doxorubicin and P300 inhibitor in liver cancer cells. These findings provide insights into mechanisms underlying dysregulation of chromatin remodelers and show novel associations between nucleoporins and chromatin remodelers in cancer. Significance: This study reveals a novel protumorigenic role for SMARCB1 and describes valuable links between nucleoporins and chromatin remodelers in cancer by identifying NUP210 as a critical coregulator of SMARCB1 chromatin remodeling activity.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-20-0568
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 7
    Online Resource
    Online Resource
    Serum small extracellular vesicle‐derived LINC00853 as a novel diagnostic marker for early hepatocellular carcinoma
    Wiley ; 2020
    In:  Molecular Oncology Vol. 14, No. 10 ( 2020-10), p. 2646-2659
    Details
    In: Molecular Oncology, Wiley, Vol. 14, No. 10 ( 2020-10), p. 2646-2659
    Abstract: This study aimed to identify novel long noncoding RNA (lncRNA) biomarkers for hepatocellular carcinoma (HCC) using publicly available tissue genomic datasets and validate their diagnostic utility for early‐stage HCC. Differentially expressed lncRNAs between 371 HCC and 50 nontumor tissues were obtained from The Cancer Genome Atlas liver hepatocellular carcinoma (TCGA_LIHC) project. Subsequently, the expression of the serum‐ and extracellular vesicle (EV)‐derived lncRNA was assessed in 10 patients with HCC and 10 healthy controls using RT–qPCR. The candidate lncRNAs were validated in 90 HCC and 92 non‐HCC (29 healthy control, 28 chronic hepatitis, 35 liver cirrhosis) patients. The sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were calculated for the candidate lncRNAs and the current HCC biomarker, alpha‐fetoprotein (AFP). SFTA1P, HOTTIP, HAGLROS, LINC01419, HAGLR, CRNDE , and LINC00853 were markedly upregulated in HCC in TCGA_LIHC dataset. Among them, LINC00853 has not been reported in relation to HCC before. In patients with HCC, only expression of small EV‐derived LINC00853 (EV‐ LINC00853) was increased. EV‐ LINC00853 showed excellent discriminatory ability in the diagnosis of all‐stage HCC (AUC = 0.934, 95% confidence interval = 0.887–0.966). Moreover, using a 14‐fold increase and 20 ng·mL −1 as cutoffs for EV‐ LINC00853 expression and AFP level, respectively, EV‐ LINC00853 was found to have a sensitivity of 93.75% and specificity of 89.77%, while AFP showed only 9.38% sensitivity and 72.73% specificity for the diagnosis of early‐stage HCC (mUICC stage I). EV‐ LINC00853 had a positivity of 97% and 67% in AFP‐negative and AFP‐positive early HCC, respectively. Serum EV‐derived LINC00853 may be a novel potential diagnostic biomarker for early HCC, especially for AFP‐negative HCC.
    Type of Medium: Online Resource
    ISSN: 1574-7891 , 1878-0261
    URL: Issue
    URL: Article
    DOI: 10.1002/mol2.v14.10
    DOI: 10.1002/1878-0261.12745
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2322586-5
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  • 8
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    Online Resource
    Depletion of NK6 Homeobox 3 (NKX6.3) causes gastric carcinogenesis through copy number alterations by inducing impairment of DNA replication and repair regulation
    Springer Science and Business Media LLC ; 2021
    In:  Oncogenesis Vol. 10, No. 12 ( 2021-12-10)
    Details
    In: Oncogenesis, Springer Science and Business Media LLC, Vol. 10, No. 12 ( 2021-12-10)
    Abstract: Genomic stability maintenance requires correct DNA replication, chromosome segregation, and DNA repair, while defects of these processes result in tumor development or cell death. Although abnormalities in DNA replication and repair regulation are proposed as underlying causes for genomic instability, the detailed mechanism remains unclear. Here, we investigated whether NKX6.3 plays a role in the maintenance of genomic stability in gastric epithelial cells. NKX6.3 functioned as a transcription factor for CDT1 and RPA1 , and its depletion increased replication fork rate, and fork asymmetry. Notably, we showed that abnormal DNA replication by the depletion of NKX6.3 caused DNA damage and induced homologous recombination inhibition. Depletion of NKX6.3 also caused copy number alterations of various genes in the vast chromosomal region. Hence, our findings underscore NKX6.3 might be a crucial factor of DNA replication and repair regulation from genomic instability in gastric epithelial cells.
    Type of Medium: Online Resource
    ISSN: 2157-9024
    URL: Article
    DOI: 10.1038/s41389-021-00365-4
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2674437-5
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