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British Journal of Cancer Oct 2023Although genome duplication, or polyploidization, is believed to drive cancer evolution and affect tumor features, its significance in hepatocellular carcinoma (HCC) is...
BACKGROUND
Although genome duplication, or polyploidization, is believed to drive cancer evolution and affect tumor features, its significance in hepatocellular carcinoma (HCC) is unclear. We aimed to determine the characteristics of polyploid HCCs by evaluating chromosome duplication and to discover surrogate markers to discriminate polyploid HCCs.
METHODS
The ploidy in human HCC was assessed by fluorescence in situ hybridization for multiple chromosomes. Clinicopathological and expression features were compared between polyploid and near-diploid HCCs. Markers indicating polyploid HCC were explored by transcriptome analysis of cultured HCC cells.
RESULTS
Polyploidy was detected in 36% (20/56) of HCCs and discriminated an aggressive subset of HCC that typically showed high serum alpha-fetoprotein, poor differentiation, and poor prognosis compared to near-diploid HCCs. Molecular subtyping revealed that polyploid HCCs highly expressed alpha-fetoprotein but did not necessarily show progenitor features. Histological examination revealed abundant polyploid giant cancer cells (PGCCs) with a distinct appearance and frequent macrotrabecular-massive architecture in polyploid HCCs. Notably, the abundance of PGCCs and overexpression of ubiquitin-conjugating enzymes 2C indicated polyploidy in HCC and efficiently predicted poor prognosis in combination.
CONCLUSIONS
Histological diagnosis of polyploidy using surrogate markers discriminates an aggressive subset of HCC, apart from known HCC subgroups, and predict poor prognosis in HCC.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; alpha-Fetoproteins; In Situ Hybridization, Fluorescence; Prognosis; Polyploidy
PubMed: 37715023
DOI: 10.1038/s41416-023-02408-6 -
International Journal of Surgery... Dec 2023In order to maximize the utilization of precious donor liver, precisely determining potential hepatocellular carcinoma (HCC) candidates who will benefit from liver...
Incorporation of protein induced by vitamin K absence or antagonist-II into transplant criteria expands beneficiaries of liver transplantation for hepatocellular carcinoma: a multicenter retrospective cohort study in China.
INTRODUCTION
In order to maximize the utilization of precious donor liver, precisely determining potential hepatocellular carcinoma (HCC) candidates who will benefit from liver transplantation (LT) is essential. As a crucial diagnostic biomarker for HCC, protein induced by vitamin K absence or antagonist-II (PIVKA-II) has become one of the key indicators for assessing tumor recurrence risk after LT. This study aims to investigate the role of PIVKA-II in recipient selection and prognostic stratification.
METHODS
The clinicopathologic data of HCC patients undergoing LT from 2015 to 2020 in six Chinese transplant centers were collected. Univariate and multivariate analyses were performed to determine risk factors for disease free survival (DFS). Based on these risk factors, survival analysis was made by Kaplan-Meier method and their value in prognostic stratification was assessed.
RESULTS
A total of 522 eligible HCC patients with pre-LT PIVKA-II records were finally included in this study. Tumor burden>8 cm, α-fetoprotein>400 ng/ml, histopathologic grade III and PIVKA-II>240 mAU/ml were identified as independent risk factors for DFS. DFS of patients with PIVKA-II≤240 mAU/ml ( N =288) were significantly higher than those with PIVKA-II>240 mAU/ml ( N =234) (1-year, 3-year, and 5-year DFS: 83.2, 77.3, and 75.9% vs. 75.1, 58.5, and 50.5%; P <0.001). Compared with Hangzhou criteria ( N =305), incorporating PIVKA-II into Hangzhou criteria (including tumor burden, α-fetoprotein, and histopathologic grade) increased the number of patients with eligibility for LT by 21.6% but achieved comparable DFS and overall survival.
CONCLUSIONS
Incorporating PIVKA-II into existing LT criteria could increase the number of eligible HCC patients without compromising post-LT outcomes.
Topics: Humans; Carcinoma, Hepatocellular; alpha-Fetoproteins; Liver Transplantation; Liver Neoplasms; Biomarkers; Retrospective Studies; Neoplasm Recurrence, Local; Living Donors; Vitamin K; Biomarkers, Tumor
PubMed: 37988413
DOI: 10.1097/JS9.0000000000000729 -
Scientific Reports Dec 2023Carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 125 (CA125), and alpha-fetoprotein (AFP) are widely used tumor markers for...
Carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 125 (CA125), and alpha-fetoprotein (AFP) are widely used tumor markers for colorectal cancer (CRC), but their clinical significance is unknown when the levels of these tumor markers were within the normal range. This retrospective study included 2145 CRC patients. The entire cohort was randomly divided into training and validation datasets. The optimal cut-off values of tumor markers were calculated using X-tile software, and univariate and multivariate analyses were performed to assess its association with overall survival (OS). The nomogram model was constructed and validated. The entire cohort was randomly divided into a training dataset (1502 cases, 70%) and a validation dataset (643 cases,30%). Calculated from the training dataset, the optimal cut-off value was 2.9 ng/mL for CEA, 10.1 ng/mL for CA19-9, 13.4 U/mL for CA125, and 1.8 ng/mL for AFP, respectively. Multivariate analysis revealed that age, tumor location, T stage, N stage, preoperative CA19-9, and CA125 levels were independent prognostic predictors. Even within the normal range, CRC patients with relatively high levels of CA19-9 or CA125 worse OS compared to those with relatively low levels. Then, based on the independent prognostic predictors from multivariate analysis, two models with/without (model I/II) CA19-9 and CA125 were built, model I showed better prediction and reliability than model II. Within the normal range, relatively high levels of preoperative CA19-9 and CA125 were significantly associated with poor OS in CRC patients. The nomogram based on CA19-9 and CA125 levels showed improved predictive accuracy ability for CRC.
Topics: Humans; Biomarkers, Tumor; Carcinoembryonic Antigen; alpha-Fetoproteins; CA-19-9 Antigen; Prognosis; Retrospective Studies; Reproducibility of Results; CA-125 Antigen; Colorectal Neoplasms
PubMed: 38129505
DOI: 10.1038/s41598-023-49832-5 -
Current Opinion in Oncology May 2024Despite the remarkable advances in the treatment of germ cell tumors (GCT), several challenges remain. This review aims to highlight some of these challenges and provide... (Review)
Review
PURPOSE OF REVIEW
Despite the remarkable advances in the treatment of germ cell tumors (GCT), several challenges remain. This review aims to highlight some of these challenges and provide guidance on how to navigate through them.
RECENT FINDINGS
Patients with International Germ Cell Cancer Collaborative Group poor risk disease have worse prognosis and investigating novel therapeutic interventions are warranted in this population. Patients with brain metastases require a multidisciplinary approach by a group of clinicians experienced in the management of germ cell tumors. Patients with platinum refractory disease have poor prognosis and development of novel treatment options is urgently needed. Conventional tumor markers including alpha fetoprotein and human chorionic gonadotropin remain standard. Development of novel biomarkers to detect minimal residual disease or teratoma is needed.
SUMMARY
Management of patients with GCT requires a multidisciplinary approach. Patients should preferably be evaluated at tertiary care centers with expertise in the management of this disease.
Topics: Humans; Neoplasms, Germ Cell and Embryonal; Teratoma; Biomarkers, Tumor; Brain Neoplasms; Neoplasm, Residual
PubMed: 38573206
DOI: 10.1097/CCO.0000000000001026 -
Open Life Sciences 2023This study aimed to investigate whether α-fetoprotein (AFP) could affect the malignant behavior of AFP-producing gastric cancer (AFP-GC) and to explore the relationship...
This study aimed to investigate whether α-fetoprotein (AFP) could affect the malignant behavior of AFP-producing gastric cancer (AFP-GC) and to explore the relationship between AFP and mesenchymal-epithelial transition factor (c-Met) in AFP-GC. In this study, 23 patients with AFP-GC (AFP[+]) and 18 patients with common gastric cancer (AFP[-]) were evaluated for the c-Met expression using immunohistochemical analysis. The AFP-GC cell line, GCIY, was used. The AFP endoribonuclease-prepared small interfering RNA (siRNA) and eukaryotic AFP overexpression vector were used to increase/knockdown the expression of AFP. Afterward, the c-Met expression was evaluated by polymerase chain reaction and western blot. The proliferation, migration, and invasion of GCIY cells were estimated before and after the AFP overexpression/knockdown. The c-Met expression in both groups was the same ( > 0.05), and AFP[+] group had a higher positive incidence of the c-Met expression than the AFP[-] group ( < 0.01). Furthermore, the c-Met expression frequency was decreased by AFP knockdown and increased by AFP overexpression ( < 0.01). The cell counting kit-8 cell proliferation assay, cell invasion, and migration assays confirmed that the AFP could affect the malignant biological behavior of AFP-GC. These findings suggest that AFP contributes to the malignant biological properties of AFP-GC and the high expression of c-Met in AFP-GC.
PubMed: 37588998
DOI: 10.1515/biol-2022-0476 -
Alimentary Pharmacology & Therapeutics Jan 2024Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer with one of the highest cancer-related mortality rates worldwide. Early diagnosis is crucial... (Review)
Review
BACKGROUND
Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer with one of the highest cancer-related mortality rates worldwide. Early diagnosis is crucial for improving the therapeutic options and reducing the disease-related mortality.
AIM
To investigate serum N-glycomics as diagnostic markers for HCC.
METHODS
We performed a comprehensive search in PubMed, EMBASE, Web of Science and Scopus through August 17, 2023. Eligible studies assessed the potential use of serum N-glycomics as diagnostic biomarkers for HCC. Study selection, data extraction and quality assessment were performed by two independent reviewers.
RESULTS
Of the 48 articles included, 11 evaluated the utility of N-glycomics for the diagnosis of HCC in whole serum while the remaining articles focused on specific protein glycoforms or protein levels. Of these specific proteins, haptoglobin, alpha-fetoprotein (AFP), kininogen (Kin), α-1-antitrypsin and Golgi protein 73 (GP73) were the most frequently studied. Increased levels of fucosylation and branching presented as the most prevalent post-translational modifications of glycoproteins in patients with HCC compared to controls. Notably, glycomics-based biomarkers may provide a clinical benefit for the diagnosis of early HCC, as several algorithms achieved AUCs between 0.92-0.97. However, these were based on single studies with limited sample sizes and should therefore be validated.
CONCLUSIONS
Alterations in serum N-glycomics, characterised by increased levels of fucosylation and branching, have potential as diagnostic biomarkers for HCC. Optimisation of study design, patient selection and analysing techniques are needed before clinical implementation will be possible.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Glycomics; alpha-Fetoproteins; Biomarkers; Glycoproteins; Biomarkers, Tumor; Liver Cirrhosis
PubMed: 37877758
DOI: 10.1111/apt.17748 -
Cellular Signalling Oct 2023Abnormal expression of Vasorin (VASN) is related to many types of cancer, but the signaling pathway and mechanism of how VASN contributes to the carcinogenesis of...
Abnormal expression of Vasorin (VASN) is related to many types of cancer, but the signaling pathway and mechanism of how VASN contributes to the carcinogenesis of hepatocellular carcinoma (HCC) are poorly understood. Here, we found that VASN was up-regulated in serum/serum exosome and tissues of HCC patients. The expression of VASN in serum improve the detection rate of HCC in alpha-fetoprotein-negative HCC patients. Immunohistochemistry revealed that VASN was highly expressed in HCC tissues and associated with different stages of HCC. Noticeably, when serum VASN combined with α-fetoprotein, the area under the curve (AUC), sensitivity, and specificity of HCC patients compared with healthy patients reached 0.918 (95% CI: 0.869-0.967, P < 0.001), 90.91%, and 90.20%, respectively. VASN knockout HCC cells were obtained by CRISPR/Cas9 and a VASN-specific monoclonal antibody was prepared by hybridoma technology. Knockout of VASN or the addition of VASN-specific monoclonal antibody suppressed the proliferation and migration of HCC. Mechanistically, VASN promote the proliferation and migration of HCC by regulating the phosphorylation of STAT3 and the expression of downstream genes CCND1 and MMP2. In conclusion, our findings suggest that VASN plays a crucial role in the activation of STAT3 signaling pathway in HCC, which is a promising target for the diagnosis and therapy of HCC.
Topics: Humans; alpha-Fetoproteins; Antibodies, Monoclonal; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Proliferation; Liver Neoplasms; Signal Transduction; STAT3 Transcription Factor
PubMed: 37454705
DOI: 10.1016/j.cellsig.2023.110809 -
World Journal of Gastrointestinal... Apr 2024Alpha-fetoprotein (AFP), a commonly used biomarker for hepatocellular carcinoma (HCC), is normal in up to one-third of patients.
BACKGROUND
Alpha-fetoprotein (AFP), a commonly used biomarker for hepatocellular carcinoma (HCC), is normal in up to one-third of patients.
AIM
To evaluate the diagnostic performance of des-gamma-carboxy-prothrombin (DCP) alone and in combination with AFP.
METHODS
In this study, 202 patients with radiologically proven HCC were enrolled, and their DCP and AFP levels were evaluated for their diagnostic performance.
RESULTS
The mean age of the enrolled patients was 58.5 years; 72.0% were male. DCP was elevated in 86.6% ( = 175) of all patients, 100.0% ( = 74) of patients with portal vein thrombus, and 87.4% ( = 111) of patients with multicentric HCC. AFP was elevated in 64.3% ( = 130) of all the patients, 74% ( = 55) of the patients with portal vein thrombus, and 71.6% ( = 91) of the patients with multicentric HCC ( = 0.030, 0.001, and 0.015, respectively). In tumors less than 2 cm in size ( = 46), DCP was increased in 32 (69.5%) patients, and AFP was increased in 25 (54.3%) patients ( = 0.801). There was good pairing between DCP and AFP for HCCs of 2 cm size or larger ( < 0.001); however, the pairing among tumors < 2 cm size was not significant ( = 0.210). In 69 of the patients (34.1%), only one of the tumor markers was positive; DCP was elevated alone in 57/202 (28.2%) of all patients, and AFP alone was elevated in 12/202 (5.9%) of the patients. The areas under receiver operating characteristic curves (AUROC) for tumors > 2 cm was 0.74 for DCP and 0.59 for AFP; combining both markers resulted in an AUROC of 0.73. For tumors < 2 cm, the AUROC was 0.25 for DCP and 0.40 for AFP.
CONCLUSION
DCP, as an individual marker, had a better diagnostic performance in many cases of HCC. Hence, DCP may replace AFP as the primary HCC biomarker.
PubMed: 38682024
DOI: 10.4291/wjgp.v15.i1.90893 -
Journal of Experimental & Clinical... Oct 2023Hepatocellular carcinoma (HCC) accounts for a majority of primary liver cancer cases and related deaths. The purpose of this study was to assess the diagnostic value of...
BACKGROUND
Hepatocellular carcinoma (HCC) accounts for a majority of primary liver cancer cases and related deaths. The purpose of this study was to assess the diagnostic value of splicing factor 3b subunit 4 (SF3B4) as a novel non-invasive biomarker for HCC and determine the association between SF3B4 expression and immune cell infiltration.
METHODS
An enzyme-linked immunosorbent assay (ELISA) was used to detect SF3B4 levels in plasma samples obtained from healthy controls (HCs) and patients with chronic hepatitis, liver cirrhosis, and HCC. The expression levels of autoantibodies that detect SF3B4 in the plasma samples of each group of patients were measured. Small extracellular vesicles (EVs) were isolated from patient sera, and the expression levels of EV-SF3B4 were measured using quantitative reverse transcription PCR.
RESULTS
ELISA results confirmed that the expression levels of SF3B4 proteins and autoantibodies in the plasma of patients with HCC were higher than those in HCs. However, their diagnostic performance was not better than that of alpha-fetoprotein (AFP). The mRNA expression of SF3B4 in serum EV increased but not in the buffy coat or serum of patients with HCC. Serum EV-SF3B4 displayed better diagnostic power than AFP for all stages of HCC (AUC = 0.968 vs. 0.816), including early-stage HCC (AUC = 0.960 vs. 0.842), and this was consistent in the external cohort. Single-cell RNA sequencing indicated that SF3B4 expression was correlated with myeloid-derived suppressor cells. The Tumor Immune Estimation Resource database reconfirmed the correlation between SF3B4 expression and immune cell infiltration in HCC.
CONCLUSIONS
SF3B4 may be associated with tumor immune infiltration in HCC, and EV-SF3B4 shows potential as a novel non-invasive diagnostic biomarker of HCC.
Topics: Humans; Carcinoma, Hepatocellular; alpha-Fetoproteins; Liver Neoplasms; Biomarkers, Tumor; RNA Splicing Factors; Extracellular Vesicles; Autoantibodies
PubMed: 37899451
DOI: 10.1186/s13046-023-02867-y -
Journal of Gastroenterology Oct 2023A large-scale multicenter study validated aldo-keto reductase 1B10 (AKR1B10) as a new serum marker of hepatocellular carcinoma (HCC). This study aimed to evaluate the...
BACKGROUND AND AIMS
A large-scale multicenter study validated aldo-keto reductase 1B10 (AKR1B10) as a new serum marker of hepatocellular carcinoma (HCC). This study aimed to evaluate the prognostic value of serum AKR1B10 in HCC.
METHODS
273 naïve HCC patients enrolled for serum AKR1B10 tests were followed up for 2 years. Survival and clinical data were collected. Kaplan-Meier survival analysis and log-rank tests were used to estimate correlation of patient survival with serum AKR1B10. Univariate and multivariate COX regression analyses were used to evaluate the prognostic value of serum AKR1B10 level independently or in combination with other clinicopathological factors. α-fetoprotein (AFP) was analyzed in parallel for comparison.
RESULTS
Serum AKR1B10 associated with tumor stage (p = 0.012), size (p = 0.004), primary tumor number (p = 0.019), and Child-Pugh classification (p = 0.003). HCC patients with a high level of serum AKR1B10 (≥ 267.9 pg/ml) had median survival (MS) of 25 months (95% confidence interval [CI] 20.788-29.212) vs. MS of 34 months (CI 28.911-39.089) in patients with normal serum AKR1B10 (p < 0.001). Univariate and multivariate COX regression analyses showed that serum AKR1B10 level was an unfavorable prognostic marker of HCC independently (HR 1.830, 95% CI 1.312-2.552; p < 0.001) or in combination with other clinical factors (HR 1.883, 95% CI 1.264-2.806; p = 0.002), such as TNM stage, tumor size and portal invasion. In the same cohort of HCC patients, AFP exhibited prognostic value at a cut-off of 400 ng/ml, but not at 20 ng/ml and 200 ng/ml.
CONCLUSIONS
Serum AKR1B10 is a new prognostic marker of HCC, better than AFP.
Topics: Humans; Carcinoma, Hepatocellular; Aldo-Keto Reductases; alpha-Fetoproteins; Liver Neoplasms; Aldehyde Reductase; Biomarkers, Tumor; Prognosis
PubMed: 37500927
DOI: 10.1007/s00535-023-02011-9