Early Diagnosis Of Liver Cancer Research Articles

CNT biodevices for early liver cancer diagnosis based on biomarkers detection- a promising platform

Regarding the serious threat of liver cancer owing to the concealment and hard detection of liver tumors at an early stage, primary diagnosis becomes quite crucial to guarantee human health. So, in this work platinum-decorated single-walled carbon nanotubes (SWCNTs) were proposed as superior nanodevice for the detection of 1-Octen-3-ol (octenol), decane, and hexanal as liver cancer biomarkers in the exhaled breath of the patients. Herein, density functional theory (DFT) calculations have been utilized to scrutinize the structural and electronic properties of pristine and Pt-decorated SWCNTs. Obtained results showed that the gas molecules were weakly physisorbed on the pristine SWCNT with negligible charge transfer and large interaction distances. Contrariwise, after the decoration of the SWCNT with Pt metal atom, significant charges are transferred, and energy adsorption increased. The results disclosed that the energy adsorption has been enhanced, for example, energy adsorption increased two times for decane and hexanal molecules (−1.06, and −1.07 eV) upon adsorption on Pt-decorated SWCNT. Moreover, substantial charges with amount of 0.238, 0.245, and 0.223 e were transferred from octenol, decane, and hexanal to the surface, respectively. So, investigations revealed that these compounds are strongly chemisorbed on Pt-SWCNT with small interaction distances and along with the short recovery time of 1.7, 83.4, and 123 s at room temperature toward octenol, decane, and hexanal, respectively which make it a compelling nanodevice. Considering the findings, Pt-SWCNT is an excellent substrate for the sense of liver cancer biomarkers with desired recovery time and the results demonstrate its feasibility for potential application in the near future in the field of liver cancer diagnosis.

Proton Magnetic Resonance Spectroscopy at 3.0T in Rabbit With VX2 Liver Cancer: Diagnostic Efficacy and Correlations With Tumor Size.

PurposesThe purpose of this study was to explore the diagnostic performance of Cho peak area (Cho Are), Cho peak amplitude (Cho Amp), and the combined approach (Cho Are_Amp) in detecting rabbit VX2 liver cancer at the early stage via hydrogen-1 proton magnetic resonance spectroscopy (1H-MRS), as well as the correlations between Cho Are, Cho Amp, and tumor parameters like diameter and volume.MethodsConventional magnetic resonance imaging (MRI) and MRS were performed to scan the VX2 liver cancer in rabbit. The tumor diameter was measured on T2-weighted imaging (T2WI), and the tumor volume was accordingly calculated. Cho Are and Cho Amp were obtained from MRS. The diagnostic performance of Cho Are, Cho Amp, and Cho Are_Amp was assessed by a receiver operating characteristic (ROC) curve and area under ROC curve (AUC), whereas specificity and sensitivity were calculated by the maximum Youden’s index. Spearman’s correlation analysis was performed to evaluate the relevance between tumor parameters (diameter, volume) and radiological indexes (Cho Are, Cho Amp).ResultsROC curve analysis showed that Cho Amp, Cho Are, and Cho Are_Amp were effective in diagnosing VX2 liver cancer. The AUC of Cho Amp was 0.883, and the specificity and sensitivity were 0.944 and 0.722, respectively (p < 0.001). The AUC of Cho Are was 0.807, and the specificity and sensitivity were 0.778 and 0.833, respectively (p < 0.05). The AUC of Cho Are_Amp was 0.892, and the specificity and sensitivity were 0.833 and 0.833, respectively (p < 0.001). Cho Are and Cho Amp exhibited a high positive correlation with tumor diameter and tumor volume, among which Cho Amp demonstrated better correlations to tumor diameter and tumor volume (r = 0.956 and 0.946) than that of Cho Are (r = 0.787 and 0.794). A high positive correlation was detected between Cho Are and Cho Amp (r = 0.787), as well as tumor diameter and tumor volume (r = 0.965).ConclusionCho Are_Amp can be used as an effective tool in diagnosing early-stage VX2 liver cancer with satisfied diagnostic accuracy. Cho Are and Cho Amp were positively correlated with tumor volume and tumor diameter. The results of this study provide further evidence that Cho Amp and Cho Are_Amp of MRS could aid in the early diagnosis of liver cancer.

Liver proliferating cell nuclear antigen, BAX/Bcl-2 ratio, collagen, and polysaccharide accumulation as diagnostic tools in experimental hepatocellular carcinoma

Objectives: This experimental study was conducted to look for a sensitive diagnostic panel for early detection of HCC.&#x0D; Methods: Combination of diethyl nitrosamine (DENA, 200 mg/kg, IP, once), two weeks later, CCl4(3ml/kg/week), subcutaneously, for 6 weeks) induced HCC in rats. Sixteen male Wistar rats were divided into 2 groups, control, and HCC.&#x0D; Results: DENA plus CCl4 elevated serum alpha-fetoprotein, liver enzyme activity and depressed superoxide dismutase, reduced glutathione (GSH), elevated malondialdehyde. Also, depressed caspase-3, elevated collagen, polysaccharide accumulation, proliferating cell nuclear antigen in liver tissues, and depressed BAX / Bcl-2 ratio. &#x0D; Conclusion: Decreased BAX/Bcl-2 ratio, elevated collagen deposition, polysaccharide accumulation, nuclear proliferation, and tissue oxidative stress help in the early diagnosis of liver cancer.

Classification of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma Based on Radiomic Analysis.

Introduction Considering the narrow window of surgery, early diagnosis of liver cancer is still a fundamental issue to explore. Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICCA) are considered as two different types of liver cancer because of their distinct pathogenesis, pathological features, prognosis, and responses to adjuvant therapies. Qualitative analysis of image is not enough to make a discrimination of liver cancer, especially early-stage HCC or ICCA. Methods This retrospective study developed a radiomic-based model in a training cohort of 122 patients. Radiomic features were extracted from computed tomography (CT) scans. Feature selection was operated with the least absolute shrinkage and operator (LASSO) logistic method. The support vector machine (SVM) was selected to build a model. An internal validation was conducted in 89 patients. Results In the training set, the AUC of the evaluation of the radiomics was 0.855 higher than for radiologists at 0.689. In the valuation cohorts, the AUC of the evaluation was 0.847 and the validation was 0.659, which indicated that the established model has a significantly better performance in distinguishing the HCC from ICCA. Conclusion We developed a radiomic diagnosis model based on CT image that can quickly distinguish HCC from ICCA, which may facilitate the differential diagnosis of HCC and ICCA in the future.

The Diagnostic Value of Contrast-Enhanced Ultrasound and Enhanced CT Combined with Tumor Markers AFP and CA199 in Liver Cancer.

Background Early screening and diagnosis are of great significance to the treatment and prognosis of patients with liver cancer. This study aims to explore the application value of contrast-enhanced ultrasound and enhanced CT combined with tumor markers alpha-fetoprotein (AFP) and carbohydrate antigen 199 (CA199) in the diagnosis of liver cancer. Methods Liver cancer group (n = 256), benign disease group (n = 110), and control group (n = 50) participated in this study. The liver cancer and benign disease groups were diagnosed pathologically by contrast-enhanced ultrasound and enhanced CT before operation. The electrochemiluminescence method was used to detect the content of AFP and CA199. And the receiver operating characteristic (ROC) curve was drawn. Results The detection rate of contrast-enhanced ultrasound is higher than that of enhanced CT. Serum levels of AFP and CA199 in the liver cancer group were significantly higher than those in the benign lesion group and the control group. The ROC curve showed that the sensitivity, accuracy, and negative prediction rate of contrast-enhanced ultrasound and enhanced CT combined with tumor markers AFP and CA199 in the diagnosis of liver cancer were significantly higher than that of a single test. Conclusion The combined detection of contrast-enhanced ultrasound and enhanced CT, AFP, and CA199 significantly improved the sensitivity and accuracy of liver cancer diagnosis. It has a significant effect on the early diagnosis of liver cancer and can be used as an important means of early screening.

An Approach to the Simultaneous Detection of Multiple Biomarkers for the Early Diagnosis of Liver Cancer Using Quantum Dot Nanoprobes

Abstract Biomarker-based early diagnosis of liver cancer is of high clinical value for reducing the mortality rate. However, it has been challenging to establish early detection methods with a single biomarker such as alpha-fetoprotein (AFP) because of limited diagnostic sensitivity and specificity. Therefore, developing multiplexed biomarker detection assays is crucially important for early diagnosis. Yet, simultaneous detection methods involving three or more biomarkers have been scarce. Here we suggest employing the serological biomarker panel of glypican-3 (GPC3), dickkopf-1 (DKK1), and AFP for liver cancer detection. We present a rapid simultaneous detection approach for the biomarker panel labeled with three fluorescent quantum dot nanoprobes (emission wavelengths at 565 nm, 605 nm, and 655 nm). As a proof-of-concept, simultaneous fluorescence detection of the biomarker panel was demonstrated using mixed reference samples containing human recombinant GPC3, DKK1, and AFP antigens. Our simultaneous detection approach conferred a linear range of 0.625-2.5 ng•mL-1 for the entire biomarker panel, which merits further clinical validation for the simultaneous and accurate determination of the biomarker panel in human serum samples.

CT-MRI Dual Information Registration for the Diagnosis of Liver Cancer: A Pilot Study Using Point-based Registration.

Early diagnosis of liver cancer may increase life expectancy. Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) play a vital role in diagnosing liver cancer. Together, both modalities offer significant individual and specific diagnosis data to physicians; however, they lack the integration of both types of information. To address this concern, a registration process has to be utilized for the purpose, as multimodal details are crucial in providing the physician with complete information. The aim was to present a model of CT-MRI registration used to diagnose liver cancer, specifically for improving the quality of the liver images and provide all the required information for earlier detection of the tumors. This method should concurrently address the issues of imaging procedures for liver cancer to fasten the detection of the tumor from both modalities. In this work, a registration scheme for fusing the CT and MRI liver images is studied. A feature point-based method with normalized cross-correlation has been utilized to aid in the diagnosis of liver cancer and provide multimodal information to physicians. Data on ten patients from an online database were obtained. For each dataset, three planar views from both modalities were interpolated and registered using feature point-based methods. The registration of algorithms was carried out by MATLAB (vR2019b, Mathworks, Natick, USA) on an Intel (R) Core (TM) i5-5200U CPU @ 2.20 GHz computer. The accuracy of the registered image is being validated qualitatively and quantitatively. The results show that an accurate registration is obtained with minimal distance errors by which CT and MRI were accurately registered based on the validation of the experts. The RMSE ranges from 0.02 to 1.01 for translation, which is equivalent in magnitude to approximately 0 to 5 pixels for CT and registered image resolution. The CT-MRI registration scheme can provide complementary information on liver cancer to physicians, thus improving the diagnosis and treatment planning process.

A new method for early diagnosis of liver cancer using a biosensor embedded in an alginate polymer thin film

Hepatocellular carcinoma (HCC) has become a pressing health problem facing the world today due to its high morbidity, high mortality, and late discovery.

Gut microbiota and immune system in liver cancer: Promising therapeutic implication from development to treatment.

Liver cancer is a leading cause of death worldwide, and hepatocellular carcinoma (HCC) is the most frequent primary liver tumour, followed by cholangiocarcinoma. Notably, secondary tumours represent up to 90% of liver tumours. Chronic liver disease is a recognised risk factor for liver cancer development. Up to 90% of the patients with HCC and about 20% of those with cholangiocarcinoma have an underlying liver alteration. The gut microbiota-liver axis represents the bidirectional relationship between gut microbiota, its metabolites and the liver through the portal flow. The interplay between the immune system and gut microbiota is also well-known. Although primarily resulting from experiments in animal models and on HCC, growing evidence suggests a causal role for the gut microbiota in the development and progression of chronic liver pathologies and liver tumours. Despite the curative intent of “traditional” treatments, tumour recurrence remains high. Therefore, microbiota modulation is an appealing therapeutic target for liver cancer prevention and treatment. Furthermore, microbiota could represent a non-invasive biomarker for early liver cancer diagnosis. This review summarises the potential role of the microbiota and immune system in primary and secondary liver cancer development, focusing on the potential therapeutic implications.

PH-Mediated Clustering of Exosomes: Breaking Through the Size Limit of Exosome Analysis in Conventional Flow Cytometry.

Exosomes have recently emerged as some of the most promising biomarkers for disease diagnosis. Due to their small sizes and composition heterogeneity, exosomes are difficult to detect by currently available platforms. Here, we report a pH-mediated assembly system that converts single nanosized exosomes into microsized clusters, which can be directly analyzed by conventional flow cytometry (FCM), breaking through the size limit of exosome analysis. We demonstrated the clinical utility of the pH-mediated clustering system by profiling the exosomal proteins from blood plasma samples of 33 cancer patients and 11 benign controls. The results indicated that the combination of MUC-1 and PD-L1 could serve as a new biomarker panel for the early diagnosis of liver cancer with high clinical accuracy. This pH-mediated assembly strategy allows rapid, sensitive, and high-throughput analysis of exosome biomarkers by conventional FCM, which can be easily refined for use in both basic and clinical settings.

Advanced electrochemical nanobiosensor for ultraefficient Annexin A2 biomarker detection: A rapid, label free and minimal invasive approach towards early diagnosis of liver cancer

Annexin A2 (ANXA2) is a highly specific and sensitive biomarker with high diagnostic accuracy, secreted in serum of liver cancer (LC) patients with an optimum cut-off value of 18 ng mL−1. In present work, we developed a nanobiosensing platform for rapid, label free and minimal invasiveelectrochemical detection of ANXA2 for early LC diagnosis. Herein, amine functionalized multi-walled carbon nanotubes (f-MWCNTs) was used as a model nanomaterial to modify indium tin oxide (ITO) coated glass substrate using electrophoretic deposition (EPD) technique (80 V, 180 s), followed by immobilization of monoclonal anti-ANXA2 using EDC-NHS chemistry. The electrochemical response of ANXA2 against the fabricated nanobiosensor was studied by cyclic voltammetry (CV), which yielded a linear detection range in between 0 to 60 ng mL−1, sensitivity of 1.805 µA mL ng−1 cm−2 with selectivity coefficient ∼1. The performance of the fabricated nanobiosensor was also validated by studying the response of ANXA2 spiked serum sample and obtained results were found in excellent correlation with the response of standard ANXA2.

Facile Functionalization Strategy for Ultrasensitive Organic Protein Biochips in Multi-Biomarker Determination.

In recent years, organic field-effect transistors (OFETs) have shown great potential for advanced protein biochips due to their inherent biocompatibility and high-throughput detectability. However, the development of OFET-based protein biochips is still at an early stage. On the one hand, single-biomarker determination is not sufficient for the diagnosis of cancer; thus, simultaneous monitoring of electrical signals toward multi-biomarkers is widely concerned and explored. On the other hand, an optimized functionalization strategy for efficient protein immobilization is another key to make OFET-based protein biochips accessible with improved detection performance. Herein, a facile functionalization strategy is developed for excellent charge-transport thin films by suppressing the gelation of diketopyrrolopyrrole (DPP)-based polymer semiconductors with the addition of the glutaraldehyde cross-linking agent. Besides, functional groups are introduced on the device surface for efficient attachment of antibodies as receptors via a condensation reaction, enabling simultaneous determination of α-fetoprotein biomarker and carcinoembryonic antigen biomarker with improved sensitivity and reliability. Therefore, the proposed high-throughput OFET-based protein biochip has the potential to be widely utilized in early liver cancer diagnosis.

The Emerging Factors and Treatment Options for NAFLD-Related Hepatocellular Carcinoma.

Simple SummaryNonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, and it is an increasing factor in the cause of hepatocellular carcinoma (HCC). The incidence of NAFLD has increased in recent decades, accompanied by an increase in the prevalence of other metabolic diseases, such as obesity and type 2 diabetes. However, current treatment options are limited. Both genetic factors and non-genetic factors impact the initiation and progression of NAFLD-related HCC. The early diagnosis of liver cancer predicts curative treatment and longer survival. Some key molecules play pivotal roles in the initiation and progression of NAFLD-related HCC, which can be targeted to impede HCC development. In this review, we summarize some key factors and important molecules in NAFLD-related HCC development, the latest progress in HCC diagnosis and treatment options, and some current clinical trials for NAFLD treatment.Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, followed by cholangiocarcinoma (CCA). HCC is the third most common cause of cancer death worldwide, and its incidence is rising, associated with an increased prevalence of obesity and nonalcoholic fatty liver disease (NAFLD). However, current treatment options are limited. Genetic factors and epigenetic factors, influenced by age and environment, significantly impact the initiation and progression of NAFLD-related HCC. In addition, both transcriptional factors and post-transcriptional modification are critically important for the development of HCC in the fatty liver under inflammatory and fibrotic conditions. The early diagnosis of liver cancer predicts curative treatment and longer survival. However, clinical HCC cases are commonly found in a very late stage due to the asymptomatic nature of the early stage of NAFLD-related HCC. The development of diagnostic methods and novel biomarkers, as well as the combined evaluation algorithm and artificial intelligence, support the early and precise diagnosis of NAFLD-related HCC, and timely monitoring during its progression. Treatment options for HCC and NAFLD-related HCC include immunotherapy, CAR T cell therapy, peptide treatment, bariatric surgery, anti-fibrotic treatment, and so on. Overall, the incidence of NAFLD-related HCC is increasing, and a better understanding of the underlying mechanism implicated in the progression of NAFLD-related HCC is essential for improving treatment and prognosis.

Diagnosis of liver cancer by FTIR spectra of serum

Liver cancer is the most common fatal malignant tumor in the world. Early diagnosis of liver cancer can improve the survival rate of the patients with liver disease. In this paper, Fourier transform infrared (FTIR) spectroscopy combined with curve fitting and chemometrics was used to distinguish the serum from patients from that of healthy people. The curve fitting results in protein range of 1700–1600 cm−1 showed that there were differences in the secondary structure of protein in serum between the patients with liver cancer and healthy people. Principal component analysis (PCA) in lipid range of 2900–2800 cm−1 could distinguish the serum of patients with liver cancer from that of healthy people. The first two principal components PC1 and PC2 explained 95% of the total data variance. The sensitivity and specificity of partial least squares discriminant analysis (PLS-DA) in lipid range of 2900–2800 cm−1 reached 92.85% and 95.23% respectively. It is shown that FTIR spectroscopy might be developed as an effective method for the diagnosis of liver cancer.

Research progress of serum biomarkers for early screening of hepatocellular carcinoma

The latest research data shows that the cause of death of liver cancer patients ranks third among malignant tumors. The global situation of early detection, early diagnosis and early treatment of liver cancer is severe. Therefore, how to achieve early diagnosis of liver cancer has important clinical significance. At present, alpha-fetoprotein, alpha-fetoprotein-L3 and des-gamma-carboxythrombin are commonly used in the clinical detection of hepatocellular carcinoma; however, their sensitivity cannot meet the diagnostic needs of patients with early liver cancer. With the development of molecular biology techniques such as serum oligosaccharide chains detection, B10, a member of the aldehyde ketone reductase family, microRNAs, circulating tumor cells, DNA methylation, and other novel serum biomarkers, a new option for the early screening and diagnosis of hepatocellular carcinoma patients will be offered.

Ultrasensitive and Reliable Organic Field-Effect Transistor-Based Biosensors in Early Liver Cancer Diagnosis.

Organic field-effect transistors (OFETs) are considered as one of the cost-effective biosensor devices with rapid detection capabilities and multiparameter responses. However, the functionalization processes on normal organic devices might impact the device performance for its further sensitive and reliable sensing applications. Herein, we develop a novel organic material, 2,6-bis(4-formylphenyl)anthracene (BFPA) for use as the protective and functional layer of OFET-based biosensors, enabling ultrasensitive determination of alpha-fetoprotein (AFP) with femtomolar accuracy in human serum. By monitoring changes of the source-drain current (Ids) and threshold voltage (Vth) electrical signals, the device exhibits improved reliability in detecting AFP biomarkers and is able to differentiate between liver cancer patients and healthy individuals. Featuring label-free determination, shorter analysis time, and lower sample volume, this ultrasensitive and reliable OFET-based biosensor displays numerous advantages over traditional strategies such as enzyme-linked immunosorbent assay and electrochemiluminescence immunoassay, demonstrating that the proposed OFET-based biosensors have broader analytical and clinical applications for early liver cancer diagnosis.

Expanding Horizon: Controllable Morphology Design of an Ecofriendly Tamarind Seedcase-Derived Porous Carbonaceous Biomass as a Versatile Electrochemical Biosensor Platform for Reactive Oxygen Species

Novel, uniform, and ordered biomass carbon materials using the skin tissue of tamarind seedcase (TS) as the carbon source were first synthesized by one-step carbonization or hydrothermal carbonization (HTC) without being template-assisted and are further explored for highly sensitive H₂O₂ biosensing. The results demonstrated that the obtained biomass carbonaceous materials (TS-C, TS powder (TSP), TSP-C, TS-HTC, and TSP-HTC) with obviously different morphologies, absorption characteristics, and pore size distributions showed variable electrocatalytic properties. TS-HTC with promising pitaya flower-like structures and a high specific surface area of 436.425 m² g–¹ presented the optimized catalytic performance for H₂O₂ detecting at the peak potential of −0.38 V. The corresponding H₂O₂ sensor displayed an outstanding sensitivity of 122.02 μA mM–¹ cm–² at the H₂O₂ concentration range of 0.05–0.5 mM and 80.79 μA mM–¹ cm–² (0.5–2.7 mM), respectively. The response time was short at 3.61 s, indicating that TS-HTC has turned out to be an attractive material for designing H₂O₂ biosensors, with a promising internally interlinked reticulate-like structure for capturing biomolecules. Moreover, the direct detection of H₂O₂ released from Hep3B cells is demonstrated on TS-HTC-based sensors, being effective to detect H₂O₂ activity in situ for the early diagnosis of liver cancer, suggesting its potential application for efficient recognition and determination of H₂O₂ in fields of life science, clinics, disease prevention, and so on.

The Application of Image Processing in Liver Cancer Detection

Hepatic cancer is caused by the uncontrolled growth of liver cells, an HCC is the most common form of malignant liver cancer, accounting for 75 percent of cases. This tumor is difficult to diagnose, and it is often discovered at an advanced stage, posing a life-threatening danger. As a result, early diagnosis of liver cancer increases life expectancy. So, using a digital image processing method, we suggest an automated computer-aided diagnosis of liver tumors from MRI images. Magnetic Resonance Imaging (MRI) images are used to identify liver tumors in this case. The image goes through image preprocessing, image segmentation, and feature extraction, all of which are done within the layers of an Artificial Neural Network, making it an automated operation. To make the edge continuous, this operation combines two processes: edge and manual labeling. On the basis of statistical characteristics, tumors are often divided into four categories: cyst, adenoma, hemangioma, and malignant liver tumor. The aim of this proposed technique is to automatically highlight and categorize tumor regions in Magnetic Resonance Imaging images without the need for a medical practitioner.

Early diagnosis and precise treatment of hepatocellular carcinoma

Liver cancer is called the "king of cancer" because of its extremely high mortality rate and lack of effective treatment methods. Effective early diagnosis of liver cancer and advance discovery period of liver cancer can effectively improve the survival rate and life cycle. Early diagnosis can be done by traditional US, CT, AFP level measurement and other methods, or by biological markers such as GPC-3, micro-RNA, and detection of some specific cell signal factors. Precision treatment is often carried out with a personalized treatment plan for the patient and a targeted therapy at the molecular level.

Application of Graphdiyne in Surface-Assisted Laser Desorption Ionization Mass Spectrometry.

Graphdiyne (GD) is a new kind of carbon nanomaterial which has carbon-carbon triple bonds to form a layered structure. Here, we report the application of GD as the matrix for small molecule analysis in laser desorption ionization mass spectrometry (LDI MS). The GD matrix displayed two advantages: little background in the low mass range and good molecular ion signal in negative ion mode for many small molecules, e.g., fatty acids, amino acids, peptides, and drugs can be obtained in negative ion mode. By comparing the signal intensity of tetraphenylborate and juglone with and without GD existing, it was found that GD can enhance both of the desorption efficiency and ionization efficiency in LDI. Through analysis of the serum samples from liver cancer patients and healthy people, the GD-assisted LDI MS results showed that fatty acids could be used as potential biomarkers for the early diagnosis of liver cancer.