Serum Biomarkers for the Prediction of Hepatocellular Carcinoma

Debes, José D.; Romagnoli, Pablo A.; Prieto, J.; Arrese, Marco; Mattos, Ângelo Zambam de; Boonstra, André

doi:10.3390/cancers13071681

Cited by 54 publications

(46 citation statements)

References 87 publications

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“…Serum proteins are the most commonly used biomarkers in clinical diagnosis and treatment monitoring, with characteristics of being rapid, less invasive, and easy to accept by patients. As reported, α‐fetoprotein (AFP) is the preferred serum marker for the diagnosis and monitoring of hepatocellular carcinoma (HCC) 3 . Cancer testis antigen sperm‐associated antigen 9 (SPAG9) could distinguish lung cancer from normal controls ( p < 0.001), and the level of the SPAG9 autoantibody in the sera of untreated patients was significantly higher than that in treated patients 4 .…”

Section: Introductionmentioning

confidence: 99%

“…As reported, αfetoprotein (AFP) is the preferred serum marker for the diagnosis and monitoring of hepatocellular carcinoma (HCC). 3 Cancer testis antigen sperm-associated antigen 9 (SPAG9) could distinguish lung cancer from normal controls (p < 0.001), and the level of the SPAG9 autoantibody in the sera of untreated patients was significantly higher than that in treated patients. 4 An increase in serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) has been associated with tumor progression and decreased overall survival of colorectal cancer.…”

Section: Introductionmentioning

confidence: 99%

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Elevated serum eotaxin and IP‐10 levels as potential biomarkers for the detection of esophageal squamous cell carcinoma

Chang

Wang

et al. 2021

Clinical Laboratory Analysis

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Background and Aims Esophageal squamous cell cancer (ESCC) is one of the leading malignant cancers with a high incidence and mortality. Exploring novel serum biomarkers will help improve the management and monitoring of ESCC. Methods In the present study, we first used a ProcartaPlex Array to screen for serum proteins that were increased in 40 ESCC patients compared with matched normal controls; we found that eight proteins (IL‐2, IL‐5, IP‐10, IL‐8, eotaxin, TNF‐α, HGF, and MIP‐1b) had higher serum levels in ESCC patients than in normal controls. We further verified the clinical relevance of the candidate biomarkers with a larger sample of sera. Results In the 174 tested ESCC patients and 189 normal controls, the serum levels of eotaxin and IP‐10 were significantly higher in patients than in normal controls (p = 0.0038, 0.0031). In particular, these two proteins were also elevated in the sera of patients with early‐stage (0‐IIA) ESCC (p = 0.0041, 0.0412). When combining CEA and CYFRA21‐1 (in use clinically) with eotaxin or IP‐10, the effectiveness of detecting ESCC was superior to that of CEA and/or CYFRA21‐1 alone. Moreover, the serum level of eotaxin dropped significantly after surgical resection of primary tumors compared with that in preoperative ESCC samples (p < 0.001). Conclusions The data suggest that serum eotaxin and IP‐10 might be potential biomarkers for the detection of ESCC.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Elevated serum eotaxin and IP‐10 levels as potential biomarkers for the detection of esophageal squamous cell carcinoma

Chang

Wang

et al. 2021

Clinical Laboratory Analysis

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“…Importantly, HCC can only be detected by specific markers (e.g. AFP) at this later stage due to the lack of early diagnostic markers, which leads to the lower survival of HCC patients (7)(8)(9). Therefore, the discovery of novel diagnostic and prognostic factors has very important clinical value in promoting the survival of HCC patients.…”

Section: Introductionmentioning

confidence: 99%

Transcription Factors and Methylation Drive Prognostic miRNA Dysregulation in Hepatocellular Carcinoma

Qin

et al. 2021

Front. Oncol.

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Many dysregulated microRNAs (miRNAs) have been suggested to serve as oncogenes or tumor suppressors to act as diagnostic and prognostic factors for HCC patients. However, the dysregulated mechanisms of miRNAs in HCC remain largely unknown. Herein, we firstly identify 114 disordered mature miRNAs in HCC, 93 of them are caused by dysregulated transcription factors, and 10 of them are driven by the DNA methylation of their promoter regions. Secondly, we find that seven up-regulated miRNAs (miR-9-5p, miR-452-5p, miR-452-3p, miR-1180-3p, miR-4746-5p, miR-3677-3 and miR-4661-5p) can promote tumorigenesis via inhibiting multiple tumor suppressor genes participated in metabolism, which may act as oncogenes, and seven down-regulated miRNAs (miR-99-5p, miR-5589-5p, miR-5589-3p, miR-139-5p, miR-139-3p, miR-101-3p and miR-125b-5p) can suppress abnormal cell proliferation via suppressing a number of oncogenes involved in cancer-related pathways, which may serve as tumor suppressors. Thirdly, our findings reveal a mechanism that transcription factor and miRNA interplay can form various regulatory loops to synergistically control the occurrence and development of HCC. Finally, our results demonstrate that this key transcription factor FOXO1 can activate a certain number of tumor suppressor miRNAs to improve the survival of HCC patients, suggesting FOXO1 as an effective therapeutic target for HCC patients. Overall, our study not only reveals the dysregulated mechanisms of miRNAs in HCC, but provides several novel prognostic biomarkers and potential therapeutic targets for HCC patients.

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“…Tumor proliferation is one of the principal markers of tumorigenesis and it is related to the growth, development, and metastasis of HCC. The mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway, also known as the Ras-RAF-MEK-ERK pathway, is involved in the HCC-associated tumor proliferation by transmitting mitogenic signals from the cell surface transmits to the nucleus (4,5). However, to date, alphafetoprotein (AFP) is the only diagnostic tumor marker available for assessing the prognosis and drug resistance in patients with HCC.…”

Section: Introductionmentioning

confidence: 99%

Tribbles pseudokinase 3 (TRIB3) contributes to the progression of hepatocellular carcinoma by activating the mitogen-activated protein kinase pathway

Wang¹,

He²,

Meng³

et al. 2021

Ann Transl Med

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Background: Tribble pseudokinase 3 (TRIB3) plays a key role in regulating the malignancy of many tumors. This study examined its function in cancer cells and explored the potential mechanisms of action.Methods: The expression of TRIB3 was examined in hepatocellular carcinomas (HCCs) using The Cancer Genome Atlas (TCGA) database. A TRIB3 lentivirus with a flag label was constructed and transfected into Huh7 and Hep3B human hepatoma cell lines to generate cells that stably overexpress TRIB3. A small interfering RNA (siRNA) was designed to knockdown TRIB3 mRNA in HepG2 and Huh7. Cell viability and cell colony formation assays were conducted. Flow cytometry was performed to assess the cell cycle in cells overexpressing TRIB3. Western blotting were performed to examine the expression of (Mitogen-activated protein kinase, MAPKK) (MEK), phosphorylated-MEK (p-MEK), extracellular signal-regulated kinase (ERK), and p-MEK in cells with TRIB3 knockdown. The correlation between TRIB3 and SMARCD3 was assessed using co-immunoprecipitation assays and immunofluorescence.Results: TRIB3 was significantly overexpressed in advanced grade HCC tissues and was closely correlated with poor prognosis. TRIB3 overexpression promoted the cell growth and cell cycle but had little effect on migration capabilities in Huh7 and Hep3B cells. Conversely, knockdown of TRIB3 had slow down the cell growth in Huh7 and HepG2 cells detected by CCK8 and colony formation assay. The expression of MEK and ERK at both the protein and mRNA levels were downregulated when TRIB3 was knocked down. The protein expression of p-ERK and p-MEK were also downregulated upon TRIB3 silencing. SMARCD3 is a transcript factor that is belongs to the SWI/SNF complex and has been shown to regulate many genes. Indeed, co-immunoprecipitation assays demonstrated that TRIB3 interacts with SMARCD3 in the nucleus, suggesting that it may regulate TRIB3 in HCCs.Conclusions: This study demonstrated that TRIB3 promotes the malignancy of HCC cells and its expression may be a potential diagnostic biomarker for HCC progression.

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Serum Biomarkers for the Prediction of Hepatocellular Carcinoma

Cited by 54 publications

References 87 publications

Elevated serum eotaxin and IP‐10 levels as potential biomarkers for the detection of esophageal squamous cell carcinoma

Elevated serum eotaxin and IP‐10 levels as potential biomarkers for the detection of esophageal squamous cell carcinoma

Transcription Factors and Methylation Drive Prognostic miRNA Dysregulation in Hepatocellular Carcinoma

Tribbles pseudokinase 3 (TRIB3) contributes to the progression of hepatocellular carcinoma by activating the mitogen-activated protein kinase pathway

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