Hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) is a major cause of morbidity and mortality in West Africa, but its presentation is poorly understood. In this study, we describe the clinical characteristics of HBV-associated HCC patients in Lagos, Nigeria. Data for all cases were collected at the emergency and gastroenterology units (2017-2019), considering chronic carriers as controls. Clinical data and routine biochemical and radiologic test results were extracted from the files. The serum biomarkers (Osteopontin, AFP-L3, DCP) were investigated. For some cases, the hepatitis B viral load was determined. The mean age of the cases (n = 92) was 41.4 years, compared to 39.9 years for the controls (n = 100). Clinically, 69.5% of cases presented with ascites, 66.3% had nodules occupying >50% of the liver, and 67.4% had moderate hepatic encephalopathy. The mean viral load and the median values of Osteopontin, AFP-L3, and DCP for the cases were significantly higher than for the controls (p < 0.001). The area under the curve, sensitivity, and specificity were significantly higher for Osteopontin, compared with DCP and AFP-L3 (p < 0.001). Most HCC patients presented at a late disease stage, when the prognosis is usually poor. Especially Osteopontin seems to have potential for early HCC detection and could possibly complement AFP and abdominal ultrasound scan for risk-group screening.

Attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy has shown significant promise in the context of liquid biopsy, offering a potential tool for cancer diagnostics. Unlike traditional tissue biopsies, which may not fully capture the clonal heterogeneity of tumors, liquid biopsy reflects the dynamic state of the disease and its progression more comprehensively. Biofluids such as serum and plasma are low-cost, minimally invasive diagnostic media with well-established clinical uses. This review assesses the use of ATR-FTIR spectroscopy to detect biochemical changes in biofluids linked to various malignancies, including breast, ovarian, endometrial, prostate, bladder, kidney, pancreatic, colorectal, hepatic, esophageal, gastric, lung, and brain cancers. While ATR-FTIR offers the advantages of rapid, minimally invasive detection and real-time disease monitoring, its integration into clinical practice faces challenges, particularly in terms of reproducibility due to variability in sample preparation, spectral acquisition, and data processing. The translation of ATR-FTIR into routine diagnostics will require validation through large-scale cohort studies and multicenter trials to ensure its clinical reliability and effectiveness.

In the setting of hepatocellular carcinoma (HCC) surveillance, a range of observations can be identified. Often, imaging findings and biochemical results are consistent with the diagnosis of HCC. However, challenges in HCC surveillance can arise in different clinical contexts, particularly when imaging results and tumor biomarkers are discordant. In this article, the authors describe 5 clinical scenarios based on our experiences in which additional evaluation was necessary to determine whether HCC was present or not.

Mounting evidence suggests that circulating microRNAs (miRNAs) hold diagnostic value in various malignancies. To identify circulating miRNAs for the early diagnosis of hepatocellular carcinoma (HCC), we conducted a meta-analysis to evaluate the diagnostic utility of miRNAs in HCC and further validated the results of the meta-analysis. English articles published prior to December 2023 were retrieved from databases including PubMed, Embase, and Web of Science. A random-effects or fixed-effects model was applied depending on the heterogeneity among studies. The pooled sensitivity, specificity, and the area under the summary receiver operating characteristic curve (AUC) were calculated to assess diagnostic accuracy. Additionally, RT-qPCR and receiver operating characteristic (ROC) analyses were employed to further validate the findings. A total of 36 studies were included, involving 3362 patients with HCC and 2150 patients with chronic hepatitis. The pooled sensitivity, specificity, and diagnostic odds ratio were 0.79 (95% CI 0.75-0.82), 0.79 (95% CI 0.73-0.84), and 14 (95% CI 9-22), respectively; the positive and negative likelihood ratios were 4.0 and 0.27, respectively; the area under the curve (AUC) in the summary receiver operating characteristic (ROC) was 0.85 (95% CI 0.82-0.88). Validation indicated a significant upregulation of miR-1246, miR-21, and miR-221 in HCC patients compared to those with chronic hepatitis (P < 0.01), while miR-122 and miR-26a were significantly downregulated (P < 0.01). Moreover, the validation results also demonstrated that serum levels of miR-21, miR-26a, miR-122, miR-221, and miR-1246 exhibit high sensitivity and specificity in the diagnosis of HCC. Circulating miRNAs may be promising biomarkers for HCC diagnosis.

Hepatocellular carcinoma (HCC) ranks as the fifth most common neoplasm and the third leading cause of cancer-related deaths worldwide. Current serum biomarkers for HCC surveillance and early diagnosis, particularly alpha-fetoprotein (AFP) the most commonly used marker, lack satisfactory sensitivity and specificity, highlighting an urgent need for more effective markers with higher accuracy for early HCC detection. The downregulation of melanoma-associated antigen D1 (MAGE-D1) transcription plays a crucial role in apoptosis and inhibits cancer cell proliferation when expressed ectopically. Moreover, reduced MAGE-D1 expression correlates with improved prognosis in many cancers. Therefore, this study aims to evaluate the diagnostic role of MAGE-D1 in HCC, proposing it as a novel biomarker for early diagnosis and monitoring of tumor progression. Serum MAGE-D1 expression was measured using RT-qPCR on 198 subjects, divided into three groups: 88 with HCC, 56 with chronic liver conditions, and 54 as healthy controls. With a sensitivity of 93.3% and a specificity of 97.5%, MAGED-1 shows strong potential as a diagnostic marker for HCC. The performance of serum MAGED-1 expression in discrimination between HCC and chronic liver condition revealed an area under the curve (AUC) of 0.939 using the cutoff (0.752) yielded a sensitivity of 90%, specificity of 85%, and an accuracy of 91%. Evaluation of the diagnostic significance of MAGED-1 demonstrated an AUC value of 0.726, with a sensitivity of 63.6% and a specificity of 73.5%. In conclusion, MAGED-1 might be a specific and sensitive biomarker for HCC, potentially improving the malignancy diagnosis and prognosis.

Acute decompensation in cirrhotic patients signifies the onset of clinically evident events due to portal hypertension. The transition from compensated to decompensated cirrhosis involves hemodynamic changes leading to multiorgan dysfunction, managed predominantly in outpatient settings with regular monitoring. The mortality risk is elevated in decompensated patients. Therefore, diligent outpatient management should focus on regular medical follow-ups, medication adjustments, patient education, addressing emergent issues and evaluation for liver transplantation. The ultimate goal is to improve quality of life, prevent disease progression, reduce complications, and assess possible recompensation. This guide provides valuable recommendations for medical experts managing decompensated cirrhotic patients post-hospitalization.

Cholangiocarcinoma (CCA) is the second most common primary malignancy of the hepatobiliary system and presents as a heterogeneous disease with three distinct morphological subtypes: mass-forming, periductal-infiltrating, and intraductal-growing, each characterized by distinguishing imaging features. Accurate diagnosis of CCA is challenging due to the overlap of imaging findings with a broad range of benign and malignant conditions. Therefore, it is essential for radiologists to recognize these mimickers and offer a reasonable differential diagnosis, as this has a significant impact on patient management. Although histopathological confirmation is often required for a definitive diagnosis, understanding specific imaging characteristics that differentiate CCA from its mimickers is crucial. This article highlights a variety of benign and malignant conditions that resemble CCA on imaging, emphasizing features that enhance diagnostic accuracy in clinical practice.

The hepatocarcinoma (HCC) is the most important liver tumor. It represents 90% of liver cancer cases. One of the main problems is the limited prompt cancer diagnosis and the advanced stages where the chances of treatment are limited. The main diagnostic methods for HCC are imaging techniques and liver biopsy. With advances in technology, proteins as significant diagnostic biomarkers have increased. The objective of this review is to describe the role of Alpha-fetoprotein (AFP), Glipican 3 (GPC-3), and Kininogen 1 (KNG-1) as biomarkers for the diagnosis of hepatocellular carcinoma. A systematic search of studies was carried out in the literature and the diagnostic values of these proteins were compared. The results showed that the combined use of biomarkers increases the diagnostic capacity for the detection of hepatocellular carcinoma.

This study aimed to investigate the diagnostic value of stress-induced phosphoprotein 1 (STIP1) in serum for hepatocellular carcinoma (HCC) and alpha-fetoprotein (AFP)-negative HCC (ANHC).

In this study, serum samples were collected from 158 HCC patients and 63 non-HCC patients. Logistic regression analysis was performed to identify independent risk factors associated with HCC and ANHC. The diagnostic values of each index for HCC and ANHC were analyzed using receiver operating characteristic (ROC) curve analysis.

The STIP1, des-γ-carboxy prothrombin (DCP), and AFP levels were higher in the HCC groups than in the non-HCC groups (P < .05). Age, DCP, STIP1, and hepatitis B virus infection were independent predictors of HCC (P < .05). The diagnostic value of STIP1 for HCC was higher than that of DCP. Additionally, age, STIP1, and hepatitis B virus infection were independent predictors for ANHC patients. The ROC curve exhibited an area under the curve value of 0.919 for STIP1, with a diagnostic cutoff value of 68.5 U/mL. Moreover, 36 ANHC patients and 19 AFP-negative non-HCC patients were included to validate the diagnostic model. A total of 20 patients had STIP1 levels greater than 68.5 U/mL, resulting in diagnostic accuracy of 67.3%, sensitivity of 55.6%, and specificity of 89.5%.

STIP1 demonstrates excellent diagnostic value for HCC and ANHC.

Hepatocellular carcinoma (HCC), a leading cause of cancer-related deaths globally, poses significant challenges in early detection. Improved diagnostic accuracy can drastically influence patient outcomes, emphasizing the need for innovative, non-invasive biomarkers.

This study utilized a cohort of 402 participants, including healthy controls, chronic hepatitis patients, and HCC patients from Bangladesh, to evaluate DNA methylation signatures in peripheral blood mononuclear cells (PBMC). We performed targeted next-generation sequencing on selected genes previously identified to assess their methylation dynamics. The development of M8 and M4 scores was based on these dynamics, using Receiver Operating Characteristic (ROC) analysis to determine their effectiveness in detecting early-stage HCC alongside existing markers such as epiLiver and alpha-fetoprotein (AFP).

Integration of M8 and M4 scores with epiLiver and AFP significantly enhances diagnostic sensitivity for early-stage HCC. The M4+epiLiver score achieves a sensitivity of 79.4% in Stage A HCC, while combining M4 with AFP increases sensitivity to 88.2-95.7% across all stages, indicating a superior diagnostic performance compared to each marker used alone.

Our study confirms that combining gene methylation profiles with established diagnostic markers substantially improves the sensitivity of detecting early-stage HCC. This integrated diagnostic approach holds promise for advancing non-invasive cancer diagnostics, potentially leading to earlier treatment interventions and improved survival rates for high-risk patients.

A highly accurate diagnostic method is crucial to reduce mortality and increase hepatocellular carcinoma (HCC) survival. Current biomarkers have limited accuracy, and novel ones are needed. Fibroblast growth factor-19 (FGF-19) is overexpressed in HCC. This study aimed to assess FGF-19 as a potential novel diagnostic biomarker for HCC.

This case-control study involved 114 individuals divided into three equal groups: HCC (n=38), Cirrhosis (n=38), and Control (n=38). HCC biomarkers included alpha-fetoprotein (AFP), Des-γ-carboxy prothrombin (DCP), and FGF-19.

The three markers, FGF-19, DCP, and AFP, were significantly different between the three groups, except that DCP was comparable between HCC and Cirrhosis groups (p=1.000). All individuals in the control group had FGF-19 levels below the minimum level in the HCC group. Thus, FGF-19 had 100% sensitivity and specificity in differentiating HCC from healthy controls. FGF-19 can discriminate between HCC and Cirrhosis groups at a 140.8 pg/mL cutoff with sensitivity and specificity of 81.8% and 87.9%, respectively. The sensitivity of FGF-19 was higher than AFP, trending toward statistical significance (p=0.095). Combining FGF-19 with AFP, DCP, or both improved sensitivity but decreased specificity.

FGF-19 is a possible noninvasive serum biomarker for HCC. Its combination with AFP or DCP improves the sensitivity for detecting HCC.

Hepatocellular carcinoma (HCC) is the most common primary liver tumor and the second leading cause of cancer-related deaths worldwide. The current study aimed to investigate the clinical relevance of the epidermal growth factor-like domain multiple 6 (EGFL6) expression in HCC and to evaluate whether the expression of EGFL6 in HCC has diagnostic and prognostic significance.

This study aimed to investigate EGFL6 protein expression levels in 260 HCC tissue specimens using immunohistochemical analyses. The immunohistochemical study demonstrated strong EGFL6 expression in the cytoplasm of non-tumor or normal hepatocytes.

The findings revealed that 98 patients exhibited low EGFL6 expression, while 162 patients displayed high EGFL6 expression. We explored the associations between cytoplasmic EGFL6 expression and the clinicopathological features of HCC. Decreased cytoplasmic EGFL6 expression exhibited significant correlations with worse cellular differentiation, higher T classification, vascular invasion, higher stage, and tumor recurrence. Survival analyses, using Kaplan-Meier survival curves for HCC patients, revealed that those with reduced cytoplasmic EGFL6 expression experienced significantly worse disease-free survival (DFS) and disease-specific survival (DSS). Univariate and multivariate analyses identified EGFL6 as an independent predictor for decreased expression, differentiation grade, vascular invasion, stage, or recurrence in cases of DFS or DSS in HCC.

This study represents, to the best of our knowledge, the first investigation into the expression of EGFL6 protein in HCC. Taken together, our findings strongly suggest that EGFL6 likely plays a crucial role in the pathogenesis of HCC and indicates that targeting EGFL6 could be a promising therapeutic strategy.

Cancer, the second leading global cause of death, impacts both physically and emotionally. Conventional treatments such as surgeries, chemotherapy, and radiotherapy have adverse effects, driving the need for more precise approaches. Precision medicine enables more targeted treatments. Genetic mapping, alongside other molecular biology approaches, identifies specific genes, contributing to accurate prognoses. The review addresses, in clinical use, a molecular perspective on treatment. Biomarkers like alpha-fetoprotein, beta-human chorionic gonadotropin, 5-hydroxyindoleacetic acid, programmed death-1, and cytotoxic T lymphocyte-associated protein 4 are explored, providing valuable information. Bioinformatics, with an emphasis on artificial intelligence, revolutionizes the analysis of biological data, offering more accurate diagnoses. Techniques like liquid biopsy are emphasized for early detection. Precision medicine guides therapeutic strategies based on the molecular characteristics of the tumor, as evidenced in the molecular subtypes of breast cancer. Classifications allow personalized treatments, highlighting the role of trastuzumab and endocrine therapies. Despite the benefits, challenges persist, including high costs, tumor heterogeneity, and ethical issues. Overcoming obstacles requires collaboration, ensuring that advances in molecular biology translate into accessible benefits for all.

Noninvasive detection of protein biomarkers in plasma is crucial for clinical purposes. Liquid chromatography-mass spectrometry (LC-MS) is the gold standard technique for plasma proteome analysis, but despite recent advances, it remains limited by throughput, cost, and coverage. Here, we introduce a new hybrid method that integrates direct infusion shotgun proteome analysis (DISPA) with nanoparticle (NP) protein corona enrichment for high-throughput and efficient plasma proteomic profiling. We realized over 280 protein identifications in 1.4 min collection time, which enables a potential throughput of approximately 1000 samples daily. The identified proteins are involved in valuable pathways, and 44 of the proteins are FDA-approved biomarkers. The robustness and quantitative accuracy of this method were evaluated across multiple NPs and concentrations with a mean coefficient of variation of 17%. Moreover, different protein corona profiles were observed among various NPs based on their distinct surface modifications, and all NP protein profiles exhibited deeper coverage and better quantification than neat plasma. Our streamlined workflow merges coverage and throughput with precise quantification, leveraging both DISPA and NP protein corona enrichment. This underscores the significant potential of DISPA when paired with NP sample preparation techniques for plasma proteome studies.

Alpha-foetoprotein (AFP) is taken as a diagnostic tumor marker for the screening and diagnosis of cancer. Nucleic acid-based isothermal amplification strategies are emerging as a potential technology in early screening and clinical diagnosis of AFP. The leakages between hairpins dramatically increase the background and reduce the sensitivity. Thus, it is necessary to develop some strategies to reduce the leakage for isothermal amplification strategies. A DNAzyme-locked leakless enzyme-free amplification system was developed for AFP detection in liver cancer and breast cancer. AFP could open the apt-hairpin and initiate the catalytic hairpin assembly (CHA) reaction to produce a Y-shaped duplex. Two tails of a Y-shaped duplex cleaved the two kinds of leakless hairpins. Then, the third tail of the Y-shaped duplex catalyzed the second CHA between the cleaved leakless hairpins to recover the fluorescent intensity. The limit of detection reached 5 fg/mL by the two levels of signal amplifications. Importantly, the leakless hairpin design effectively reduced leakage between hairpins and weakened the background. In addition, it also showed a great promising potential for AFP detection in early screening and clinical diagnosis.

Background: Alpha-fetoprotein (AFP) and carbohydrate antigen 19-9 (CA 19-9) are two tumor markers that are widely used in the differential diagnosis in patients with primary liver tumors. Very high levels of AFP are sporadically observed in patients with intrahepatic cholangiocarcinoma (ICC) and may cause an incorrect initial diagnosis of hepatocellular carcinoma (HCC). Methods: Two cases of tumors in cirrhotic livers were described, in which the initial diagnosis, based on very high AFP levels (Patient I: 10,464 ng/mL, Patient II: 2212 ng/mL, reference range: ≤8.04 ng/mL) was HCC. In addition, the PubMed database was searched for cases of ICC with elevated AFP. Discussion: In both individuals, liver cirrhosis was diagnosed, but there was no typical rapid "washout" in the contrast-enhanced computed tomography. Based on the histological assessment of samples obtained in the core biopsies, the initially assumed diagnosis of HCC was changed to ICC in both cases. Only nine cases of patients with ICC and high AFP levels were found in the PubMed database. The AFP levels ranged from slightly elevated to over 16,000 ng/mL. Conclusions: A very high AFP level does not necessarily correlate with the presence of HCC. Therefore, the diagnosis has to be verified histologically, when the radiological imaging is uncertain in patients with liver cirrhosis.

Hepatocellular carcinoma (HCC) is much rarer in children and adolescents in comparison to adults with an incidence of 0.7/1,000,000 per year. Hepatitis B virus, a known carcinogen increases the chances of HCC at a young age. Very few case reports of HCC developing in HBV-positive male children have been published.We present a case of a 14-year-old Hepatitis B-positive boy who presented with abdominal distension and jaundice. Contrast enhanced computerized tomography (CECT) whole abdomen suggested a diagnosis of multinodular HCC with no evidence of metastasis on FDG PET-CECT. Histopathology with immunohistochemistry confirmed the diagnosis of moderately differentiated HCC.Clinical presentation of HCC in children is similar to adults. Viral hepatitis, metabolic disorders, and male gender increase the risk of HCC. In our case, boy never had any prior history of jaundice, abdominal pain/distension, or any other illness suggestive of liver dysfunction. When the boy was found to be HBV positive, his mother was also screened and turned out to be Hepatitis B virus positive. Histopathology along with a panel of immunohistochemical markers clinched the final diagnosis.

Hepatoblastoma (HB) is the most common pediatric hepatic malignancy. Despite the progress in HB treatment, investigating HB pathomechanisms to optimize stratification and therapies remains a focal point to improve the outcome for high-risk patients.

Here, we pointed to explore the impact of these mechanisms in HB. An observational study was performed on liver samples from a cohort of 17 patients with a diagnosis of HB and two normal liver samples. The in vitro experiments were executed on the Huh6 human HB cell line treated with the FAK inhibitor TAE226.

Our results highlight a significant up-regulation of mRNA and protein expression of FAK in livers from HB with respect to normal livers. The increased protein expression of total and Tyr397 phosphorylated FAK (pTyr397FAK) was significantly correlated with the expression of some epigenetic regulators of histone H3 methylation and acetylation. Of note, the expression of pTyr397FAK, N-methyltransferase enzyme (EZH2) and tri-methylation of the H3K27 residue correlated with tumor size and alpha-fetoprotein (AFP) levels. Finally, TAE226 caused a significant reduction of pTyr397FAK, epigenetic regulators, AFP, EPCAM, OCT4, and SOX2, in association with anti-proliferative and pro-apoptotic effects on HB cells.

Our results suggest a role of FAK in HB that requires further investigations mainly focused on the exploration of its effective diagnostic and therapeutic translatability.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Although alpha-fetoprotein (AFP) has been used for 60+ years as an HCC diagnostic serum marker, its accuracy is debated. Notably, the role of interleukin 10 (IL-10) in cancer development and metastasis is elevated in various tumor types, including HCC and chronic HCV infection. Our study aimed to investigate the diagnostic performance of IL-10 and AFP as biomarkers for HCV-induced HCC in an Egyptian population.

Eighty participants were recruited and categorized into three groups: HCV-related HCC (n=40), HCV-related cirrhosis (n=40), and control (n=20).The collected blood samples were analyzed to evaluate liver function, AFP levels, and IL-10 levels.

Our analysis showed that AFP demonstrated low sensitivity (40% false-negative) and low specificity (33% false-positive).IL-10 levels were significantly higher (P < 0.001) in patients with HCC than in the cirrhosis and control groups. The serum AFP and IL-10 combination revealed significantly increased sensitivity (97.5%), diagnostic accuracy (71.1%), AUC (0.798), PPV (73.3%), and NPV ( 69.5%) when compared with either of them alone.

the reliability of AFP as a major HCC marker was poor. However, IL-10 levels are a novel biomarker for the degree of HCC inflammation, considering IL-10's potential role in HCV-HCC development. We suggest combining AFP with IL-10 to improve the diagnostic and prognostic value of HCC considerably. Future research on these biomarkers should prioritize their clinical validity, prognostic usefulness, and compatibility with other therapeutic approaches as immunotherapy.

The "one drug-one target" paradigm has various limitations affecting drug efficacy, such as resistance profiles and adverse effects. Combinational therapies help reduce unexpected off-target effects and accelerate therapeutic efficacy. Sorafenib- an FDA-approved drug for liver cancer, has multiple limitations. Therefore, it is recommended to identify an agent that increases its effectiveness and reduces toxicity. In this regard, Apigenin, a plant flavone, would be an excellent option to explore.

We used in silico, in vitro, and animal models to explore our hypothesis. For the in vitro study, HepG2 and Huh7 cells were exposed to Apigenin (12-96 μM) and Sorafenib (1-10 μM). For the in vivo study, Diethylnitrosamine (DEN) (25 mg/kg) induced tumor-bearing animals were given Apigenin (50 mg/kg) or Sorafenib (10 mg/kg) alone and combined. Apigenin's bioavailability was checked by UPLC. Tumor nodules were studied macroscopically and by Scanning Electron Microscopy (SEM). Biochemical analysis, histopathology, immunohistochemistry, and qRT-PCR were done.

The results revealed Apigenin's good bioavailability. In silico study showed binding affinity of both chemicals with p53, NANOG, ß-Catenin, c-MYC, and TLR4. We consistently observed a better therapeutic efficacy in combination than alone treatment. Combination treatment showed i) better cytotoxicity, apoptosis induction, and cell cycle arrest of tumor cells, ii) tumor growth reduction, iii) increased expression of p53 and decreased Cd10, Nanog, ß-Catenin, c-Myc, Afp, and Tlr4.

In conclusion, Apigenin could enhance the therapeutic efficacy of Sorafenib against liver cancer and may be a promising therapeutic approach for treating HCC. However, further research is imperative to gain more in-depth mechanistic insights.

Liquid biopsy is a very topical issue in clinical diagnostics research nowadays. In this study, we explored and compared various analytical approaches to blood plasma analysis. Finally, we proposed a comprehensive procedure, which, thanks to the utilization of multiple analytical techniques, allowed the targeting of various biomolecules in blood plasma reflecting diverse biological processes underlying disease development. The potential of such an approach, combining proteomics, metabolomics, and vibrational spectroscopy along with preceding blood plasma fractionation, was demonstrated on blood plasma samples of patients suffering from hepatocellular carcinoma in cirrhotic terrain (n = 20) and control subjects with liver cirrhosis (n = 20) as well as healthy subjects (n = 20). Most of the applied methods allowed the classification of the samples with an accuracy exceeding 80.0 % and therefore have the potential to be used as a stand-alone method in clinical diagnostics. Moreover, a final panel of 48 variables obtained by a combination of the utilized analytical methods enabled the discrimination of the hepatocellular carcinoma samples from cirrhosis with 94.3 % cross-validated accuracy. Thus, this study, although limited by the cohort size, clearly demonstrated the benefit of the multimethod approach in clinical diagnosis.

Cancer biomarkers have revolutionized the field of oncology by providing valuable insights into tumor changes and aiding in screening, diagnosis, prognosis, treatment prediction, and risk assessment. The emergence of "omic" technologies has enabled biomarkers to become reliable and accurate predictors of outcomes during cancer treatment.

In this review, we highlight the clinical utility of biomarkers in cancer identification and motivate researchers to establish a personalized/precision approach in oncology. By extending a multidisciplinary technology-based approach, biomarkers offer an alternative to traditional techniques, fulfilling the goal of cancer therapeutics to find a needle in a haystack.

We target different forms of cancer to establish a dynamic role of biomarkers in understanding the spectrum of malignancies and their biochemical and molecular characterization, emphasizing their prospective contribution to cancer screening. Biomarkers offer a promising avenue for the early detection of human cancers and the exploration of novel technologies to predict disease severity, facilitating maximum survival and minimum mortality rates. This review provides a comprehensive overview of the potential of biomarkers in oncology and highlights their prospects in advancing cancer diagnosis and treatment.

Non-invasive detection of protein biomarkers in plasma is crucial for clinical purposes. Liquid chromatography mass spectrometry (LC-MS) is the gold standard technique for plasma proteome analysis, but despite recent advances, it remains limited by throughput, cost, and coverage. Here, we introduce a new hybrid method, which integrates direct infusion shotgun proteome analysis (DISPA) with nanoparticle (NP) protein coronas enrichment for high throughput and efficient plasma proteomic profiling. We realized over 280 protein identifications in 1.4 minutes collection time, which enables a potential throughput of approximately 1,000 samples daily. The identified proteins are involved in valuable pathways and 44 of the proteins are FDA approved biomarkers. The robustness and quantitative accuracy of this method were evaluated across multiple NPs and concentrations with a mean coefficient of variation at 17%. Moreover, different protein corona profiles were observed among various nanoparticles based on their distinct surface modifications, and all NP protein profiles exhibited deeper coverage and better quantification than neat plasma. Our streamlined workflow merges coverage and throughput with precise quantification, leveraging both DISPA and NP protein corona enrichments. This underscores the significant potential of DISPA when paired with NP sample preparation techniques for plasma proteome studies.

Hepatocellular carcinoma (HCC) is the most common primary liver tumor and is associated with high mortality rates. Approximately 80% of cases occur in cirrhotic livers, posing a significant challenge for appropriate therapeutic management. Adequate screening programs in high-risk groups are essential for early-stage detection. The extent of extrahepatic tumor spread and hepatic functional reserve are recognized as two of the most influential prognostic factors. In this retrospective multicenter study, we utilized machine learning (ML) methods to analyze predictors of mortality at the time of diagnosis in a total of 208 patients. The eXtreme gradient boosting (XGB) method achieved the highest values in identifying key prognostic factors for HCC at diagnosis. The etiology of HCC was found to be the variable most strongly associated with a poorer prognosis. The widely used Barcelona Clinic Liver Cancer (BCLC) classification in our setting demonstrated superiority over the TNM classification. Although alpha-fetoprotein (AFP) remains the most commonly used biological marker, elevated levels did not correlate with reduced survival. Our findings suggest the need to explore new prognostic biomarkers for individualized management of these patients.

Hepatocellular carcinoma (HCC) has high incidence and mortality rates, and it is characterized by invasiveness, poor prognosis, and limited treatment opportunities. The objective of our research was to assess the role of circ_0016142 in HCC. The ferroptosis inducer RSL3 and the iron chelator deferoxamine were used to treat cells to induce or inhibit ferroptosis, respectively, and cell viability and proliferation were assessed in Hep3B and HA22T cells by CCK8 and EdU assays, respectively. ROS, MDA, GSH, and Fe2+ levels were determined using commercial kits. RT-qPCR and western blotting were performed to determine the relative expression levels of entities of interest. Dual-luciferase reporter and RNA pull-down assays were performed to assess the relationship between circ_0016142/GPX4 and miR-188-3p. The results showed that circ_0016142/GPX4 was overexpressed, whereas miR-188-3p was downregulated in HCC. Circ_0016142 silencing reduced cell proliferation and GSH levels and increased ROS, MDA, and Fe2+ levels in HCC cells, and this was reversed by the miR-188-3p inhibitor. GPX4-overexpression abolished the effect of miR-188-3p mimic in HCC cells. In conclusion, circ_0016142 silencing suppressed HCC cell proliferation by inducing ferroptosis via the miR-188-3p/GPX4 axis.

As normal cells transform into cancers, their cell state changes, which may drive cancer cells into a stem-like or more primordial, foetal, or embryonic cell state. The transcriptomic profile of this final state may encode information about cancer's origin and how cancers relate to their normal cell counterparts.

Here, we used single-cell atlases to study cancer transformation in transcriptional terms. We utilised bulk transcriptomes across a wide spectrum of adult and childhood cancers, using a previously established method to interrogate their relationship to normal cell states. We extend and validate these findings using single-cell cancer transcriptomes and organ-specific atlases of colorectal and liver cancer.

Our bulk transcriptomic data reveals that adult cancers rarely return to an embryonic state, but that a foetal state is a near-universal feature of childhood cancers. This finding was confirmed with single-cell cancer transcriptomes.

Our findings provide a nuanced picture of transformation in human cancer, indicating cancer-specific rather than universal patterns of transformation pervade adult epithelial cancers.

Background Hepatocellular carcinoma (HCC) represents the most common primary liver malignancy, with a high fatality rate. Relatively, Saudi Arabia has a high incidence of HCC, which is detected in later stages with a poor prognosis. This study aims to investigate the patterns, outcomes, and mortality predictors of HCC in Saudi Arabia. Method A retrospective study from April 2018 to June 2022 included patients with HCC who were diagnosed and managed at the Najran Oncology Center, Saudi Arabia. Through our cancer registry, the patients' clinical, laboratory, radiological, and survival profiles were extracted and analyzed to assess factors associated with mortality using a univariate analysis. The overall survival was calculated by the Kaplan-Meier method. Results The study involved 52 patients with an average age of 74.6 years, predominantly male (the male-to-female ratio is 2.25:1). Viral infections were the primary cause of liver disease in 40.3% (n=21) of patients. At diagnosis, the Child-Pugh class distribution included 23.1% (n=12) patients in class A, 36.5% (n=19) patients in class B, and 40.4% (n=21) patients in class C. Uninodular tumors with ≤50% liver extension were observed in 65.4% (n=34) of cases, and 30.8% (n=16) had portal vein thrombosis. Elevated alpha-fetoprotein (AFP) levels were noted in 48.1% (n=25) of patients, with 23.1% (n=12) exceeding 400 ng/mL. Curative resection was performed in 32.7% (n=17) of patients. The mean survival time was 23±11.8 months (median of 22.5 months, minimum of six, and maximum of 49 months). Relapse occurred in seven (13.5%) cases, while new metastasis occurred in 20 (38.5%) cases. During the study period, 26 (50.0%) patients died. The main cause of death was disease progression in 15 (28.8%) patients. Univariate analysis showed that AFP>400 ng/mL (OR: 4.68; 95% CI: 1.87-11.66, p=0.001), presence of relapse (OR: 0.16; 95% CI: 0.03-0.78, p=0.023), abdominal ascites (OR: 3.38; 95% CI: 1.25-9.14, p=0.016), advanced the Cancer of the Liver Italian Program (CLIP) score (OR: 0.60; 95% CI: 0.41-0.88, p=0.009) were associated with higher mortality rate and were statistically significant. Conclusion Most cases of HCC in our patients were attributed to viral hepatitis, with the majority having liver cirrhosis. Higher AFP (>400 ng/mL), relapse, abdominal ascites, and a higher cancer CLIP score were associated with poorer outcomes. Targeted screening and health education should be advocated; in addition, social determinants should be proactively addressed.

Biomarkers are vital in healthcare as they provide valuable insights into disease diagnosis, prognosis, treatment response, and personalized medicine. They serve as objective indicators, enabling early detection and intervention, leading to improved patient outcomes and reduced costs. Biomarkers also guide treatment decisions by predicting disease outcomes and facilitating individualized treatment plans. They play a role in monitoring disease progression, adjusting treatments, and detecting early signs of recurrence. Furthermore, biomarkers enhance drug development and clinical trials by identifying suitable patients and accelerating the approval process. In this review paper, we described a variety of biomarkers applicable for cancer detection and diagnosis, such as imaging-based diagnosis (CT, SPECT, MRI, and PET), blood-based biomarkers (proteins, genes, mRNA, and peptides), cell imaging-based diagnosis (needle biopsy and CTC), tissue imaging-based diagnosis (IHC), and genetic-based biomarkers (RNAseq, scRNAseq, and spatial transcriptomics).

Primary hepatocellular carcinoma (HCC) is one of the most prevalent world-wide malignancies. Half of the newly developed HCC occurs in China. Optimizing the strategies for high-risk surveillance and early diagnosis are pivotal for improving 5-year survival. Constructing the scientific non-invasive detection technologies feasible for medical and healthcare institutions is among the key routes for elevating the efficacies of HCC identification and follow-up.

Based on the Chinese and international guidelines, expert consensus statements, literatures and evidence-based clinical practice experiences, this consensus statement puts forward the clinical implications, application subjects, detection techniques and results interpretations of the triple-biomarker (AFP, AFP-L3%, DCP) based GALAD, GALAD like models for liver cancer.

The compile of this consensus statement aims to address and push the reasonable application of the triple-biomarker (AFP, AFP-L3%, DCP) detections thus to maximize the clinical benefits and help improving the high risk surveillance, early diagnosis and prognosis of HCC.

Hepatocellular carcinoma (HCC) has high recurrence rates exceeding 50% despite curative resection. The serum biomarker alpha-fetoprotein (AFP) is a well-known prognostic marker for HCC. EpCAM-positive circulating tumor cells (CTC) have a high predictive value for early HCC recurrence after curatively intended resection, most likely indicating micro-metastases at the time of resection. However, sensitivity remains low. The objective of this study was to evaluate a composite test comprising both CTC and AFP to identify patients at high risk for early HCC recurrence. We prospectively enrolled 58 patients undergoing curative intended resection for HCC at a tertiary referral center. Blood specimens were obtained prior to resection and analyzed for EpCAM-positive CTC and serum AFP levels. A positive result was defined as either detection of CTC or AFP levels ≥ 400 ng/ml. Eight patients tested positive for CTC, seven for AFP, and two for both markers. A positive composite test was significantly associated with shorter early recurrence-free survival (5 vs. 16 months, p = 0.005), time to recurrence (5 vs. 16 months, p = 0.011), and overall survival (37 vs. not reached, p = 0.034). Combining CTC and AFP identified patients with poor outcome after surgical resection, for whom adjuvant or neoadjuvant therapies may be particularly desirable.

This study aims to describe the diagnostic performance of alpha-fetoprotein (AFP), alpha-fetoprotein L3 isoform (AFP-L3), protein induced by vitamin K absence II (PIVKA-II), and combined biomarkers for non-B non-C hepatocellular carcinoma (NBNC-HCC).

A total of 681 newly-diagnosed primary liver disease subjects (385 non-HCC, 296 HCC) who tested negativity for the hepatitis B surface antigen (HBsAg) and hepatitis C antibody (anti-HCV) enrolled in this study. At the cut-off point of 3.8 ng/mL, AFP helps to discriminate HCC from non-HCC with an area under the curve (AUC) value of 0.817 (95% confidence interval [CI]: 0.785-0.849). These values of AFP-L3 (cut-off 0.9%) and PIVKA-II (cut-off 57.7 mAU/mL) were 0.758 (95%CI: 0.725-0.791) and 0.866 (95%CI: 0.836-0.896), respectively. The Bayesian Model Averaging (BMA) statistic identified the optimal model, including patients' age, aspartate aminotransferase, AFP, and PIVKA-II combination, which helps to classify HCC with better performance (AUC = 0.896, 95%CI: 0.872-0.920, P < 0.001). The sensitivity and specificity of the optimal model reached 81.1% (95%CI: 76.1-85.4) and 83.2% (95%CI: 78.9-86.9), respectively. Further analyses indicated that AFP and PIVKA-II markers and combined models have good-to-excellent performance detecting curative resected HCC, separating HCC from chronic hepatitis, dysplastic, and hyperplasia nodules.

Liquid biopsy, particularly cell-free RNA (cfRNA), has emerged as a promising non-invasive diagnostic tool for various diseases, including cancer, due to its accessibility and the wealth of information it provides. A key area of interest is the composition and cellular origin of cfRNA in the blood and the alterations in the cfRNA transcriptomic landscape during carcinogenesis. Investigating these changes can offer insights into the manifestations of tissue alterations in the blood, potentially leading to more effective diagnostic strategies. However, the consistency of these findings across different studies and their clinical utility remains to be fully elucidated, highlighting the need for further research in this area.

In this study, we analyzed over 350 blood samples from four distinct studies, investigating the cell type contributions to the cfRNA transcriptomic landscape in liver cancer. We found that an increase in hepatocyte proportions in the blood is a consistent feature across most studies and can be effectively utilized for classifying cancer and healthy samples. Moreover, our analysis revealed that in addition to hepatocytes, liver endothelial cell signatures are also prominent in the observed changes. By comparing the classification performance of cellular proportions to established markers, we demonstrated that cellular proportions could distinguish cancer from healthy samples as effectively as existing markers and can even enhance classification when used in combination with these markers.

Our comprehensive analysis of liver cell-type composition changes in blood revealed robust effects that help classify cancer from healthy samples. This is especially noteworthy, considering the heterogeneous nature of datasets and the etiological distinctions of samples. Furthermore, the observed differences in results across studies underscore the importance of integrative and comparative approaches in the future research to determine the consistency and robustness of findings. This study contributes to the understanding of cfRNA composition in liver cancer and highlights the potential of cellular deconvolution in liquid biopsy.

Combination of immune-checkpoint inhibitor (ICI) and vascular endothelial growth factor (VEGF) antagonist has become the first line systemic treatment for advanced hepatocellular carcinoma (HCC). However, two-thirds of patients do not respond to ICI-based treatments and biomarkers for response remain elusive.

Patients with advanced HCC who received Atezolizumab/Bevacizumab combination or Nivolumab during 2016-2022 were identified in our Liver Cancer Database. Retrospective review of their clinical data was performed to investigate parameters that could be predictive of immunotherapy response.

96 patients received Atezolizumab/Bevacizumab (n=60) or Nivolumab (n=36). Median age at diagnosis was 67.1 years. 70 patients had received treatment and 26 patients were treatment naïve before starting immunotherapy. Mean pre-treatment AFP was 9780.7 (±32035) ng/mL. Confirmed objective response (complete or partial) was seen in 29% of the population (n=27). Disease remained stable in 12% (n=11) and progressed in 60% (n=56). On univariate analysis, pre-treatment AFP>400 ng/mL was associated with objective response (OR=4.5, 95% CI:1.7-11.9, p=0.0015), while white race (OR=0.35, 95% CI:0.13-0.92, p=0.030) and prior radiotherapy (OR=0.14, 95% CI:0.01-1.1, p=0.033) or systemic therapy with TKIs (OR=0.25, 95% CI:0.08-0.81, p=0.017) were associated with poor response. On multivariate analysis only AFP>400 ng/mL remained associated with response (OR=3.7, 95% CI:1.3-10.5, p=0.014). Overall survival (OS) at one and three years was 86% and 43% in responders, and 45% and 29% in non-responders, respectively.

In our institutional experience, treatment naivety and pre-treatment AFP>400 ng/mL were associated with objective response. Prospective studies aimed at identifying factors associated with response to immunotherapy will aide patient selection.

Hepatocellular carcinoma epidemiological data are limited in France. The Epidemio Liver Immunotherapy Tecentriq outcome research (ELITor) retrospective study, based on real-world data from the Carcinome HépatocellulaIrE en France (CHIEF) French cohort of hepatocellular carcinoma patients, aimed to get insight into the treatment patterns, the sociodemographic, clinical, biological, and etiological characteristics, and the quality of life of patients with unresectable hepatocellular carcinoma.

Between 1 September 2019 and 4 December 2020, 367 patients from the CHIEF cohort received at least one locoregional (52.8%) chemoembolization or radioembolization or systemic treatment (88.3%) and were selected for ELITor. Most patients had a Barcelona Clinic Liver Cancer (BCLC) C (93.2%) hepatocellular carcinoma stage and were affected by cirrhosis (67.7%). Alcohol was confirmed as the main etiology both as a single etiology (29.1%) and in association with other risk factors (26.9%), mainly metabolic disorders (16.2%).Tyrosine-kinase inhibitors, mainly sorafenib, were the most administered systemic treatments in first line. Patients who received at least one combination of atezolizumab and bevacizumab during the study period ( N  = 53) had a better performance status and less portal hypertension frequency than the overall population and more hepatitis B virus infection and fewer metabolic disorders as single etiology. Overall, the global health score before treatment (62.3 ± 21.9) was in line with that of reference cancer patients and worsened in 51.9% of the cases after first-line palliative-intent treatment.

This study provided real-life data on advanced hepatocellular carcinoma characteristics and treatment patterns and described the first patients to receive the atezolizumab-bevacizumab combination before it became the new standard of care for advanced hepatocellular carcinoma.

Extracellular vesicles (EVs) play critical roles in intercellular communication by transporting bioactive cargo to recipient cells. EVs have been implicated in a range of physiological and pathological processes, including tumor progression, metastasis, immune modulation, and drug resistance. The objective of this review is to present a thorough overview of recent studies focusing on EVs in hepatocellular carcinoma (HCC), with an emphasis on their potential utility as diagnostic biomarkers as well as therapeutic agents. Initially, we explore the utility of EVs as diagnostic biomarkers for HCC, followed by a discussion of their potential as carriers of therapeutic payloads. Additionally, we delve into the emerging field of therapeutic EVs for modulating tumor immune responses. Through this review, our ultimate aim is to provide a comprehensive understanding of the opportunities and challenges in the clinical translation of EV research in the domain of HCC.

Hepatocellular carcinoma (HCC) is the most common liver cancer and has a propensity to develop arteriovenous fistulas with the surrounding vasculature, making targeted intravascular treatment more difficult. HCC can oftentimes be accompanied by portal hypertension and liver cirrhosis, which can, in turn, cause recanalization of the umbilical vein. In rare circumstances, arteriovenous fistula formation and shunting into the recanalized and enlarged umbilical vein can occur. In the following presented case of HCC, an arteriovenous shunt between the anterior division of the right hepatic artery and a recanalized umbilical vein is demonstrated. Subsequent successful endovascular coil embolization of the fistula was performed to avoid shunting and non-target embolization of the radiation particles in the umbilical vein territory. Post-embolization angiogram with DynaCT and lack of Tc-99m macroaggregated albumin deposition in the umbilical vein distribution confirmed the resolution of the shunt. The patient then received targeted Y-90 transarterial radioembolization locoregional therapy in combination with systemic therapy.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Although alpha fetoprotein (AFP) remains a commonly used serological marker of HCC, the sensitivity and specificity of AFP in detecting HCC is often limited. Exosomal RNA has emerged as a promising diagnostic tool for various cancers, but its use in HCC detection has yet to be fully explored. Here, we employed Machine Learning on 114,602 exosomal RNAs to identify a signature that can predict HCC. The exosomal expression data of 118 HCC patients and 112 healthy individuals were stratified split into Training, Validation and Unseen Test datasets. Feature selection was then performed on the initial training dataset using permutation importance, and the predictive performance of the selected features were tested on the validation dataset using Support Vector Machine (SVM) Classifier. A minimum of nine features were identified to be predictive of HCC and these nine features were then evaluated across six different models in an unseen test set. These features, mainly in the immune, platelet/neutrophil and cytoskeletal pathways, exhibited good predictive performance with ROC-AUC from 0.79-0.88 in the unseen test set. Hence, these nine exosomal RNAs have potential to be clinically useful minimally invasive biomarkers for HCC.

Inappropriate testing remains a high healthcare cost driver. Tumour marker tests are more expensive than routine chemistry testing. Implementing test demand management systems like electronic gatekeeping (EGK) has reportedly decreased test requests.

This study aimed to describe the appropriateness of tumour marker tests, carcinoembryonic antigen, alpha foetal protein, prostate-specific antigen, carbohydrate antigen 19-9, cancer antigen 15-3, cancer antigen 125, and human chorionic gonadotropin, and determine the effectiveness of the EGK used in the public health sector in KwaZulu-Natal, South Africa.

Tumour marker test data for the KwaZulu-Natal province were extracted from the National Health Laboratory Service Central Data Warehouse for 01 January 2017 - 30 June 2017 (pre-EGK) and 01 January 2018 - 30 June 2018 (post-EGK implementation). Questionnaires were sent to the clinicians in the regional hospitals ordering the most tumour marker tests to assess ordering practices. In addition, we assessed monthly rejection reports to determine the effect of the EGK.

The EGK minimally reduced tumour marker requests or associated costs (1.4% average EGK rejection rate). An overall 18% increase in the tumour marker tests occurred in 2018. The data suggest inappropriate tumour marker test utilisation, particularly for screening.

The introduction of EGK as a test demand management had little impact on tumour marker test requests and costs. Continuous education and reiteration of indications for tumour marker test use are required.

This study demonstrates the ineffectiveness of EGK in tumour marker orders, and provides some insight as to why these markers are being ordered, which is important in trying to decrease inappropriate ordering of these tests.

Various studies have reported cell-free RNAs (cfRNAs) as noninvasive biomarkers for detecting hepatocellular carcinoma (HCC). However, they have not been independently validated, and some results are contradictory. We provided a comprehensive evaluation of various types of cfRNA biomarkers and a full mining of the biomarker potential of new features of cfRNA.

We first systematically reviewed reported cfRNA biomarkers and calculated dysregulated post-transcriptional events and cfRNA fragments. In 3 independent multicentre cohorts, we further selected 6 cfRNAs using RT-qPCR, built a panel called HCCMDP with AFP using machine learning, and internally and externally validated HCCMDP's performance.

We identified 23 cfRNA biomarker candidates from a systematic review and analysis of 5 cfRNA-seq datasets. Notably, we defined the cfRNA domain to describe cfRNA fragments systematically. In the verification cohort (n = 183), cfRNA fragments were more likely to be verified, while circRNA and chimeric RNA candidates were neither abundant nor stable as qPCR-based biomarkers. In the algorithm development cohort (n = 287), we build and test the panel HCCMDP with 6 cfRNA markers and AFP. In the independent validation cohort (n = 171), HCCMDP can distinguish HCC patients from control groups (all: AUC = 0.925; CHB: AUC = 0.909; LC: AUC = 0.916), and performs well in distinguishing early-stage HCC patients (all: AUC = 0.936; CHB: AUC = 0.917; LC: AUC = 0.928).

This study comprehensively evaluated full-spectrum cfRNA biomarker types for HCC detection, highlighted the cfRNA fragment as a promising biomarker type in HCC detection, and provided a panel HCCMDP.

National Natural Science Foundation of China, and The National Key Basic Research Program (973 program).