NCOA5 has been identified as a crucial factor in the progression of hepatocellular carcinoma (HCC). This study investigates the expression of NCOA5 in HCC, revealing its significant overexpression in tumor tissues compared to healthy liver tissues, as evidenced by analysis of the TCGA dataset and RT-qPCR in patient samples. Higher NCOA5 levels correlate with poor overall survival, highlighting its role as a prognostic indicator. Furthermore, our findings suggest that elevated NCOA5 is associated with resistance to sorafenib, a common chemotherapeutic agent for HCC, as shown through analysis of publicly available datasets and the establishment of sorafenib-resistant HCC cell lines. Mechanistically, NCOA5 appears to inhibit ferroptosis in HCC cells by modulating glutathione peroxidase 4 (GPX4) levels. Knockdown of NCOA5 sensitizes resistant cell lines to sorafenib and induces ferroptosis by decreasing GPX4 expression. Additionally, NCOA5 regulation of GPX4 is mediated through the transcription factor MYC. In vivo studies further validate that targeting NCOA5 enhances the efficacy of sorafenib in resistant HCC models by promoting ferroptosis. Collectively, these findings underscore the potential of NCOA5 as a therapeutic target to overcome drug resistance in HCC, providing insights into its role in modulating treatment responses and patient prognosis.

Hepatocellular carcinoma (HCC) poses a significant global burden as a highly prevalent and life-threatening malignant tumor that endangers human life and wellbeing. The purpose of this study was to examine how DNA methylation-driven genes impact the prognosis of HCC patients.

Differentially expressed genes from The Cancer Genome Atlas, GSE76427, GSE25097 and GSE14520 datasets were collected to perform differential expression analysis between HCC patients and controls. Weighted gene coexpression network analysis (WGCNA) was subsequently performed to create coexpression modules for the DEGs. Then, ssGSEA was employed to investigate the infiltration of immune cells in HCC. Enrichment analysis and methylation were carried out for the module genes. We utilized Kaplan-Meier survival analysis to assess patient prognosis.

Eight coexpression modules were identified via WGCNA for 1927 upregulated and 1,231 downregulated DEGs, after which the hub genes of the modules were identified. Module 5 had high immune infiltration, and the hub gene SCAMP3 was positively associated with Tcm. Module 3 exhibited a low level of immune infiltration, and the expression of the hub gene HCLS1 was negatively correlated with T cells and dendritic cells. Furthermore, we obtained five hub genes (BOP1, BUB1B, NOTCH3, SCAMP3, and SNRPD2) as methylation-driven genes. BOP1 and BUB1B were found to be correlated with unfavorable overall survival in patients with HCC.

HCLS1 and SCAMP3 are associated with immunity, whereas BOP1 and BUB1B are modified by methylation and may serve as prognostic markers for HCC.

Programmed cell death (PCD) is a significant factor in the progression of hepatocellular carcinoma (HCC) and might serve as a crucial marker for predicting HCC prognosis and therapy response. However, the classification of HCC based on diverse PCD patterns requires further investigation. This study identified a novel molecular classification named PCD subtype (C1, C2, and C3) based on the genes associated with 19 PCD patterns, distinguished by clinical, biological functional pathways, mutations, immune characteristics, and drug sensitivity. Validated in 4 independent datasets, diverse cell death pathways were enriched in the C3 subtype, including apoptosis, pyroptosis, and autophagy, it also exhibited a highly infiltrative immunosuppressive microenvironment and demonstrated higher sensitivity to compounds such as Paclitaxel, Bortezomib, and YK-4-279, while C1 subtype was significantly enriched in cuproptosis and metabolism-related pathways, suggesting that it may be more suitable for cuproptosis-inducing agent therapy. Subsequently, utilizing the machine learning algorithms, we constructed a cell death-related index (CDRI) with 22 gene features and constructed prognostic nomograms with high predictive performance by combining CDRI with clinical features. Notably, we found that CDRI effectively predicted the response of HCC patients to therapeutic strategies, where patients with high CDRI were more suitable for sorafenib drug therapy and patients with low CDRI were more ideal for transarterial chemoembolization (TACE). In conclusion, the PCD subtype and CDRI demonstrate significant efficacy in predicting the prognosis and therapeutic outcomes for patients with HCC. These findings offer valuable insights for the development of precise, individualized treatment strategies.

Hepatocellular carcinoma (HCC) remains the leading cause of cancer-related mortality worldwide and is characterized by high recurrence rates after curative resection. The tumor markers des-gamma-carboxy prothrombin (DCP) and alpha-fetoprotein (AFP) are crucial for HCC diagnosis and prognosis. However, their roles in the modern era of HCC epidemiology require reevaluation.

This multi-institutional retrospective study analyzed 1515 patients who underwent hepatectomy for primary HCC. Patients were classified into 4 clusters using k-means analysis based on preoperative DCP and AFP levels. Clinicopathologic characteristics, overall survival (OS), and recurrence rate (RR) were evaluated using Cox proportional hazards models and area under the receiver operating characteristic curve (AUROC) comparisons.

Cluster 3 (concurrent elevations of DCP and AFP) had the poorest 5-year OS (52.8%) and the highest RR (79.3%), whereas cluster 4 (low levels of both markers) had the most favorable outcomes, with a 5-year OS rate of 71.5% and an RR of 55.7%. Cluster 1 (elevated DCP alone) was associated with larger tumors (median of 45 mm) and more frequent vascular invasion (43%) than cluster 2 (elevated AFP alone, median tumor size of 24 mm, and vascular invasion of 36%). DCP was a stronger predictor of 5-year OS in patients with preserved liver function (AUROC, 0.63), whereas AFP was more effective in stratifying RR in patients with impaired liver function (AUROC, 0.57). Non-B, non-C hepatitis (NBNC)-related HCC exhibited a distinct biomarker profile, with an elevated DCP level correlating with a higher 5-year RR (67%) than other etiologies.

Our study introduces tumor marker clustering as a novel analytical approach, providing a nuanced understanding of AFP and DCP's combined utility in predicting prognosis and recurrence. Our findings highlight the independent and complementary roles of these biomarkers, particularly in NBNC-related HCC and in cases with impaired liver function. AFP and DCP remain crucial tools for recurrence risk assessment, guiding personalized management strategies, such as surveillance, neoadjuvant therapies, and tailored postoperative interventions.

Atezolizumab plus bevacizumab is a commonly used first-line regimen for advanced hepatocellular carcinoma (HCC) treatment owing to its superior outcomes compared to sorafenib. However, optimal subsequent treatment options for patients with HCC who progressed on first-line atezolizumab plus bevacizumab remain unclear.

This multinational, multi-institutional, retrospective study included patients with HCC from 22 centers in five Asia-Pacific countries who were treated with first-line atezolizumab plus bevacizumab, which was discontinued for any reason. The endpoints included progression-free survival (PFS) and overall survival (OS) according to patient characteristics and second-line regimens.

Between June 2016 and May 2023, 1,141 patients were treated with first-line atezolizumab plus bevacizumab, of whom 629 (55.1%) received subsequent treatment. Sorafenib and lenvatinib were the most commonly administered second-line regimens (53.9% and 25.6%, respectively). Overall, the median PFS and OS were 2.9 and 8.0 months, respectively. Lenvatinib had longer PFS (4.0 vs. 2.3 months) and OS (8.0 vs. 6.3 months) than sorafenib. Patients treated with tyrosine kinase inhibitor (TKI) plus immune checkpoint inhibitor (ICI) (n = 50, 8.3%) showed PFS and OS of 5.4 and 12.6 months, respectively. Lower tumor burden and lenvatinib or TKI plus ICI use were associated with longer second-line PFS. Preserved liver function was associated with improved OS.

In patients with HCC who progressed on first-line atezolizumab plus bevacizumab, sorafenib and lenvatinib were the most commonly used second-line regimens in Asia-Pacific countries, with lenvatinib resulting in longer OS than sorafenib. The second-line TKI plus ICI combination exhibited promising efficacy, suggesting the potential role of continuing ICIs beyond disease progression.

Hepatobiliary cancers present a significant challenge to global health. Saudi Arabia and adjacent Gulf nations experience considerable impacts from these cancers. Numerous risk factors have contributed to the increasing prevalence of these cancers. The primary cases are linked to several factors, including hepatitis viral infection, smoking, alcohol consumption, diabetes mellitus, obesity or being overweight, liver cirrhosis, nonalcoholic fatty liver disease, hemochromatosis, aflatoxins, anabolic steroids, and genetic predisposition. Data regarding hepatobiliary cancers is scarcely obtained from Saudi Arabia. This research aims to clarify the epidemiology and risk factors linked to hepatobiliary cancers in Saudi Arabia. Our investigation revealed a lack of studies that collectively examine hepatocellular cancers in Saudi Arabia, highlighting a distinctive element of the current review. To determine the incidence, prevalence, risk factors, and other epidemiological metrics of hepatobiliary cancer in Saudi Arabia, a search was conducted using Medline/PubMed, Scopus, Web of Knowledge, Google Scholar, and relevant public databases that fulfilled the inclusion criteria. An electronic search was conducted using various keywords related to hepatobiliary cancer in Saudi Arabia. In summary, hepatobiliary cancers exhibit significant prevalence in Saudi Arabia, especially liver cancer. Commonly recognized risk factors for type 2 diabetes mellitus encompass tobacco and alcohol consumption, obesity or overweight status, and viral hepatitis.

Lenvatinib, an oral molecular target drug used for the treatment of hepatocellular carcinoma (HCC), has a high protein binding rate, resulting in high variability of free drug concentration in blood depending on patient conditions and drug interactions. In this study, an ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) assay was established to measure free lenvatinib concentrations. The novel assay was used to measure free lenvatinib concentrations in plasma of HCC patients, and the effect of hepatic dysfunction on free lenvatinib concentrations was evaluated.

We studied 31 HCC patients treated orally with lenvatinib at Oita University Hospital. Blood samples were collected at seven time points on the first day of lenvatinib administration to measure total and free lenvatinib concentrations using UHPLC-MS/MS.

Pharmacokinetic (PK) parameters were calculated, and hepatic function was assessed using Child-Pugh (CP) classification and CP score. Patients were divided into CP class A (n = 22) and class B (n = 9), and PK parameters were compared between the two groups. The CP class B group had significantly higher trough concentrations (Ctrough) of total and free lenvatinib as well as Ctrough normalized to dose (Ctrough/Dose) compared to the class A group. A significant positive correlation was found between CP score and both Ctrough and Ctrough/Dose of total and free lenvatinib. However, free lenvatinib concentration tended to reflect the effects of hepatic function decline more sensitively than total concentration. In addition, plasma albumin concentration correlated significantly with protein binding rate.

The results of this study indicate that free lenvatinib concentration may reflect the effects of declining hepatic function more sensitively than total lenvatinib concentration. Therefore, measurement of free lenvatinib concentration may be clinically useful in patients with impaired hepatic function.

Microvascular invasion (MVI) is an independent risk factor for the recurrence and metastasis of hepatocellular carcinoma (HCC), associated with poor prognosis. Thus, MVI has significant clinical value for the treatment selection and prognosis assessment of patients with HCC. However, there is no reliable and precise method for assessing the postoperative prognosis of MVI patients. This study aimed to develop a new HCC prognosis prediction model based on MVI characteristic genes through spatial transcriptomics sequencing, distinguishing between high-risk and low-risk patients and evaluating patient prognosis. In this study, four MVI samples with different grades were selected for spatial transcriptomic sequencing to screen for MVI region-specific genes. On this basis, an HCC prognostic model was constructed using univariate Cox regression analysis, LASSO regression analysis, random survival forest, and stepwise multivariate Cox regression analysis methods. We constructed a 7-gene prognostic model based on MVI characteristic genes and demonstrated its applicability for predicting the prognosis of HCC patients in three external validation cohorts. Furthermore, our model showed superior predictive performance compared with three published HCC prediction prognostic models and could serve as an independent prognostic factor for HCC. Additionally, single nucleus RNA sequencing analysis and multiple immunofluorescence images revealed an increased proportion of macrophages in high-risk patient samples, suggesting that HCC tumor cells may promote HCC metastasis through MIF-CD74 cell interactions. To sum up, we have developed a 7-gene biomarker based on MVI that can predict the survival rate of HCC patients at different stages. This predictive model can be used to categorize into high- and low- risk groups, which is of great significance for the prognostic assessment and personalized treatment of HCC patients.

Non-alcoholic Fatty Liver Disease (NAFLD) - whose terminology was recently replaced by metabolic liver disease (MAFLD) - is an accumulation of triglycerides in the liver of >5 % of its weight. Epidemiological studies indicated an association between NAFLD and reduced physical activity. In addition, exercise has been shown to improve NAFLD independently of weight loss. In this paper, we aim to systematically review molecular changes in sedentary experimental NAFLD models vs. those subjected to exercise. We utilized the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist and standard review techniques. Studies were considered for inclusion if they addressed the primary question: the mechanisms by which exercise influenced NAFLD. This review summarized experimental evidence of improvements in NAFLD with exercise in the absence of weight loss. The pathways involved appeared to have AMPK as a common denominator. See also the graphical abstract(Fig. 1).

Mint3 enhances aerobic ATP production with subsequent nuclear translocation of hypoxia-inducible factor-1 (HIF-1) and activation of angiogenesis-related genes. It remains unclear if and when Mint3 is activated and whether it is involved in hepatocarcinogenesis. We explored the expression of Mint3 in surgically resected hepatocellular carcinoma (HCC) tissues. We evaluated the effects of Mint3 knockdown on spheroid formation capacity and subcutaneous tumor growth in immune-deficient mice. We used Mint3 knockout mice to evaluate the effects of chemically induced HCC development. Mint3 was overexpressed in well-differentiated HCC with the activation of HIF-1 target genes irrespective of the absence of hypervascularization. Mint3 knockdown ameliorated the expression of HIF-1 target genes in patient-derived HCC cell lines and suppressed spheroid formation. Mint3 knockdown further inhibited subcutaneous tumor formation in vivo in immune-deficient mice. Chemical HCC development induced by N-nitrosodiethylamine (DEN) or DEN/CCl4 was dramatically suppressed in Mint3 knockout mice compared to control mice. Mint3 plays a crucial role in early-stage HCC development before hypervascularization by activating HIF-1 target genes before the tumor becomes hypoxic. Mint3 is a molecular target that prevents HCC development in the early stages.

Aristolochic acid I (AAI) is one of the nephrotoxic and carcinogenic compounds in Aristolochic acids (AAs). Recent studies have reported its promoting effect on hepatocellular carcinoma. However, the underlying mechanisms of AAI for the development of HCC is still unclear. Here, we found that AAI exposure caused alterations in mitochondrial function, which featured with increased ATP level and mitochondrial membrane potential, accumulation of mitochondrial Ca2+ and mitochondrial ROS (MitoROS) in Hepa1-6 and HepG2 cells. The restriction of mitochondrial Ca2+ uptake alleviated these effects. Our results showed that increased MitoROS was associated with AAI-induced migration and invasion in HCC cells. MitoROS/Src/FAK pathway was involved in the AAI-induced migration and invasion of HCC cells. In summary, our study showed that AAI affected mitochondrial metabolism of HCC cells by promoting the accumulation of mitochondrial Ca2+. These effects resulted in the activation of the MitoROS/SRC/FAK pathway in AAI-treated HCC cells, which in turn induced cell migration and invasion.

The study highlights that RPS21, a gene encoding a component of the 40S ribosomal subunit, plays an oncogenic role in hepatocellular carcinoma (HCC) and may influence tumor aggressiveness by affecting antioxidant capacity. RPS21 was found to be upregulated in HCC through RNA-sequencing of clinical samples and analysis of the TCGA database. Kaplan-Meier survival analyses linked higher RPS21 expression to lower survival rates across multiple metrics (OS, PFS, RFS, DSS). Mutation analysis via the cBioPortal showed that primarily amplifications in RPS21 are associated with a poorer prognosis. Tissue microarrays confirmed higher RPS21 levels in tumor samples, which were associated with more advanced clinical stages and grades. Experimental interventions involving lentiviral knockdown or overexpression of RPS21 significantly altered HCC cell proliferation and migration. These findings were supported by mouse models, which showed impacts on tumor growth and metastasis. Further mechanistic studies indicated that RPS21 modulates the ubiquitination and stability of GPX4, a key player in ferroptosis and oxidative stress regulation in HCC cells. This comprehensive study, which merges bioinformatic analysis with laboratory research, positions RPS21 as a viable target for HCC therapy and opens new pathways for understanding and treating liver cancer.

Aim: The present study aimed to compare the long-term survival outcomes of hepatic resection (HR) and radiofrequency ablation (RFA) in patients with single small (≤2 cm) hepatocellular carcinoma (HCC).Materials & methods: This retrospective study enrolled patients with a single small HCC measuring 2 cm or smaller underwent HR or RFA as their initial treatment.Results: Overall survival (OS) was significantly higher in the HR group than in the RFA group, while no significant difference was observed in recurrence free survival (RFS) between the two groups. However, after propensity score matching, both OS and RFS in the HR group were significantly higher than in the RFA group. Multivariate analysis showed that patients with hepatitis B virus infection, elevated prothrombin-induced by vitamin K absence or antagonist-II, and albumin-bilirubin (ALBI) grade 2/3 before treatment had poorer OS. Patients with ALBI grade 1 in the HR group demonstrated the highest OS.Conclusion: HR showed significantly better long-term OS and RFS compared with RFA in patients with as a single HCC (≤2 cm). Moreover, the ALBI grade may help identify patients who would benefit from HR or RFA.

The aim of our research was to explore the character of autophagy related 12 (ATG12) in the development of hepatocellular carcinoma (HCC). A total of  145 HCC tissues as well as paired adjacent normal tissues were collected, then immunohistochemistry was conducted to access the expression of ATG12. HCC cells were transfected with pcDNA ATG12 or si-ATG12 to overexpress ATG12 or downregulate ATG12. The vitality of HCC cells was accessed using CCK-8 assay, and the ability of invasion of them was tested through Transwell assay. The apoptotic rate of HCC cells was calculated by flow cytometry. The expression of ATG12 was lower in HCC tissues than that in normal tissues, and HCC patients with high ATG12 level survived longer. Overexpressed of ATG12 restrained vitality and invasion of HCC cells, while elevated apoptotic rate of HCC cells. Silence of ATG12 expression yielded opposite results to overexpression of ATG12 in HCC cells. In conclusion, ATG12 is low expressed in HCC, which attenuated the growth and invasion of HCC, while induced the apoptosis of HCC cells. Current research suggested that ATG12 might be a potential target for the diagnosis and treatment of HCC.

Patients with human immunodeficiency virus (HIV) are more susceptible to liver cancer because of their compromised immune system. There is no specific prognostic model for HIV-infected hepatocellular carcinoma (HCC) patients.

Clinical data of 85 patients with HIV-infected HCC was divided into a 7:3 ratio for training and internal validation sets, while the data of 23 patients with HIV-infected HCC was served as the external validation set. Data of 275 HIV-negative HCC patients was considered as external HIV-negative validation set. Variables associated with overall survival (OS) in the training set were used to develop the HIV-infected HCC prognosis (HIHP) model. The model was tested in the internal and external validation sets. The predictive accuracy of the model was assessed with conventional HIV-negative HCC prognostic scoring systems.

In the training set, variables independently associated with OS in multivariable analysis were organ involvement and tumor number. The HIHP model demonstrated a significant association with OS in the training set, with a median OS of 13 months for low risk, 7 months for medium risk, and 3 months for high risk (p < 0.001). The HIHP model showed a significant association with OS, and exhibited greater discriminative abilities compared to conventional HIV-negative HCC prognostic models both in the internal and external validation sets. In the external HIV-negative validation set, the HIHP model did not show better discrimination than conventional HIV-negative HCC scores.

The new model presented in the work provided a more accurate prognostic prediction of OS in HIV-infected HCC patients. However, the model is not applicable to patients with HIV-negative HCC.

Globally, nearly half of deaths from cirrhosis and chronic liver diseases (CLD) and three-quarters of deaths from hepatocellular carcinoma (HCC) occur in the Asia-Pacific region. Chronic hepatitis B is responsible for the vast majority of liver-related deaths in the region. Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common form of CLD, affecting an estimated 30% of the adult population. Compared with people of European descent, people from the Asia-Pacific region carry more genetic variants associated with MASLD and its progression. Alcohol is a fast-growing cause of CLD and HCC in Asia as a result of the rising per-capita consumption of alcohol. Drug-induced liver injury is under-recognized and probably has a high prevalence in this region. The epidemiological and outcome data of acute-on-chronic liver failure are heterogeneous, and non-unified definitions across regions contribute to this heterogeneity. CLDs are severely underdiagnosed, and effective treatments and vaccinations are underutilized. In this Review, we highlight trends in the burden of CLD and HCC in the Asia-Pacific region and discuss the rapidly changing aetiologies of liver disease. We examine the multiple gaps in the care cascade and propose mitigating strategies and future directions.

Hepatocellular carcinoma (HCC) is prevalent in Taiwan, primarily due to the high incidence of hepatitis B and C infections, with high recurrence rates of 50-70% within five years after initial treatment. Treatment options for recurrent HCC include salvage liver transplantation, trans-arterial chemoembolization, re-hepatectomy, and radiofrequency ablation. Repeat hepatectomy exhibits superior oncological outcomes compared with alternative approaches. Although laparoscopic liver resection has demonstrated safety and feasibility for primary HCC resection, the persistence of intrahepatic recurrence necessitates effective intervention. However, repeat liver resection poses several challenges including adhesions from previous surgeries, limited access to recurrent tumors, altered liver structure post-regeneration, difficulties in obtaining hilar control, and compromised liver reserves. Suggesting a laparoscopic approach for recurrent HCC is typically based on the surgeons' experience and confidence. In this study, we reconfirmed the safety, feasibility and oncological outcome of laparoscopic repeat liver resection and investigated the optimal timing for initiation of this procedure by a pioneering team in minimally invasive liver resection.

We retrospectively reviewed our collective experience of 57 patients with recurrent HCC between January 2009 and December 2021.The patients were followed until June 30, 2024. Among them, 37 underwent laparoscopic approaches and 20 opted for open procedures.

Both groups exhibited similar operative times and perioperative outcomes, with significantly reduced hospital stays in the laparoscopic cohort (median: 5 vs. 7, p < 0.001). The median follow-up duration was 41.5 months (range, 2.8 to 112.6 months). Mortality occurred in 22 patients (38.6%) and recurrence occurred in 26 patients (45.6%) The overall survival and disease-free survival after the operation were similar in both groups and comparative to the literatures.

Using a stepwise approach, laparoscopic repeat liver resection can be performed safely and effectively with a low incidence of conversion by an experienced surgical team with similar oncological outcomes. The introduction of laparoscopic techniques has also sparked a strategic shift in the surgical approach for recurrent HCC. This treatment option should be offered to patients by an experienced surgical team for minimally invasive liver resections.

The rapid advances in laparoscopic surgery have meant that formerly complex techniques are now commonly performed via this method. These practices are now becoming increasingly popular in the discipline of hepatopancreaticobiliary (HPB) surgery. One such example is liver resection, which is the focus of our review. We aimed to assess the rate of bile leak complications in minimally invasive liver resection compared to an open liver approach in malignant and benign conditions. A systematic review spanning the period from 2000 to 2022 was conducted, examining the postoperative complications in laparoscopic versus open liver resections. We searched the databases Medline, Cochrane, PubMed, and Google Scholar for relevant studies; 16 studies were included in the final analysis. Ten out of 16 studies that were included indicated that there was no significant difference in the rate of bile leaks. Five studies showed that bile leaks were found to occur more frequently in open surgery, and one study suggested that the rates were more common with the laparoscopic approach. The overall comparison of bile leak rates following open and minimally invasive liver resection suggests that there is no reduction in this complication in both types of surgery. As such, a laparoscopic or open method can both be adopted without any concerns for this particular complication.

In this editorial, we comment on an original article by Duan et al. Despite advancements in the diagnosis and treatment of hepatocellular carcinoma (HCC), the identification of suitable prognostic factors remains challenging. In their paper, Duan et al identified long non-coding RNAs (LncRNAs) to quantify genomic instability (GI) by combining LncRNA expression and somatic mutation profiles. They confirmed that the GI-derived LncRNA signature (GI-LncSig) could be an independent prognostic factor with the area under the curve of 0.773. Furthermore, the authors stated that GI-LncSig may have a better predictive performance than TP53 mutation status alone. However, studies exploring genetic markers for predicting the prognosis of HCC are crucial for identifying therapeutic targets and enhancing diagnostic and treatment strategies to mitigate the global burden of liver cancer.

This study investigated the image quality and detectability of double low-dose hepatic multiphase CT (DLDCT, which targeted about 30% reductions of both the radiation and iodine concentration) using a vendor-agnostic deep-learning-based contrast-boosting model (DL-CB) compared to those of standard-dose CT (SDCT) using hybrid iterative reconstruction.

The CT images of 73 patients with chronic liver disease who underwent DLDCT between June 2023 and October 2023 and had SDCT were analyzed. Qualitative analysis of the overall image quality, artificial sensation, and liver contour sharpness on the arterial and portal phase, along with the hepatic artery clarity was conducted by two radiologists using a 5-point scale. For quantitative analysis, the image noise, signal-to-noise ratio, and contrast-to-noise ratio were measured. The lesion conspicuity was analyzed using generalized estimating equation analysis. Lesion detection was evaluated using the jackknife free-response receiver operating characteristic figures-of-merit.

Compared with SDCT, a significantly lower effective dose (16.4 ± 7.2 mSv vs. 10.4 ± 6.0 mSv, 36.6% reduction) and iodine amount (350 mg iodine/mL vs. 270 mg iodine/mL, 22.9% reduction) were utilized in DLDCT. The mean overall arterial and portal phase image quality scores of DLDCT were significantly higher than SDCT (arterial phase, 4.77 ± 0.45 vs. 4.93 ± 0.24, AUCVGA 0.572 [95% CI, 0.507-0.638]; portal phase, 4.83 ± 0.38 vs. 4.92 ± 0.26, AUCVGA 0.535 [95% CI, 0.469-0.601]). Furthermore, DLDCT showed significantly superior quantitative results for the lesion contrast-to-noise ratio (7.55 ± 4.55 vs. 3.70 ± 2.64, p < 0.001) and lesion detectability (0.97 vs. 0.86, p = 0.003).

In patients with chronic liver disease, DLDCT using DL-CB can provide acceptable image quality without impairing the detection and evaluation of hepatic focal lesions compared to SDCT.

Cholangiocarcinoma (CCA) is a heterogeneous and aggressive malignancy with limited therapeutic options and poor prognosis. The identification of reliable prognostic biomarkers and a deeper understanding of the molecular subtypes are critical for the development of targeted therapies and improvement of patient outcomes. This study aims to uncover oxidative stress-related genes (ORGs) in CCA and develop a prognostic risk model using comprehensive transcriptomic analysis from The Cancer Genome Atlas (TCGA). Through LASSO regression analysis, we identified prognosis-related ORGs and constructed a prognostic signature consisting of six ORGs. This signature demonstrated strong predictive performance in survival analysis and ROC curve assessment. Functional enrichment and GSEA analyses revealed significant enrichment of immune-related pathways among different risk groups. GSVA analysis indicated reduced activity in inflammation and oxidative stress pathways in the high-risk subgroup, and xCell results showed lower immune cell infiltration levels in this group. Additionally, immune checkpoint genes and immune-related pathways were downregulated in the high-risk subgroup. Our research has developed a unique prognostic model focusing on oxidative stress, enabling accurate forecasting of patient outcomes and providing crucial insights and recommendations for the prognosis of individuals with CCA. Future studies should aim to validate these findings in clinical settings and further explore therapeutic targets within oxidative stress pathways.

To identify the risk factors and construct a predictive model for early recurrence of hepatitis B virus(HBV-)- related hepatocellular carcinomas(HCCs) after radical resection.

A total of 465 HBV-related HCC patients underwent radical resections between January 1, 2012 and August 31, 2018.Their data were collected through the inpatient information management system of the First Affiliated Hospital of University of Science and Technology of China. Survival and subgroup analyses of early recurrence among male and female patients were performed using Kaplan-Meier curves. The independent risk factors associated with early postoperative tumor recurrence were analyzed using multivariate Cox proportional hazards regression model. Based on these independent risk factors, a risk function model for early recurrence was fitted, and a column chart for the prediction model was drawn for internal and external validation.

A total of 181 patients developed early recurrences, including 156 males and 25 females. There was no difference in the early recurrence rates between males and females. Tumor diameters>5cm, microvascular invasion and albumin level<35 g/L were independent risk factors for early recurrence. A nomogram for the early recurrence prediction model was drawn; the areas under the curve for the model and for external verification were 0.638 and 0.655, respectively.

Tumor diameter>5 cm, microvascular invasion, and albumin level<35 g/L were independent risk factors for early recurrence. The prediction model based on three clinical indicators could predict early recurrence, with good discrimination, calibration, and extrapolation.

This work presents the implementation of an RGB-D camera as a surrogate signal for liver respiratory-induced motion estimation. This study aims to validate the feasibility of RGB-D cameras as a surrogate in a human subject experiment and to compare the performance of different correspondence models.

The proposed approach uses an RGB-D camera to compute an abdominal surface reconstruction and estimate the liver respiratory-induced motion. Two sets of validation experiments were conducted, first, using a robotic liver phantom and, secondly, performing a clinical study with human subjects. In the clinical study, three correspondence models were created changing the conditions of the learning-based model.

The motion model for the robotic liver phantom displayed an error below 3 mm with a coefficient of determination above 90% for the different directions of motion. The clinical study presented errors of 4.5, 2.5, and 2.9 mm for the three different motion models with a coefficient of determination above 80% for all three cases.

RGB-D cameras are a promising method to accurately estimate the liver respiratory-induced motion. The internal motion can be estimated in a non-contact, noninvasive and flexible approach. Additionally, three training conditions for the correspondence model are studied to potentially mitigate intra- and inter-fraction motion.

To explore the predictive performance of tumor and multiple peritumoral regions on dynamic contrast-enhanced magnetic resonance imaging (MRI), to identify optimal regions of interest for developing a preoperative predictive model for the grade of microvascular invasion (MVI).

A total of 147 patients who were surgically diagnosed with hepatocellular carcinoma, and had a maximum tumor diameter ≤ 5 cm were recruited and subsequently divided into a training set (n = 117) and a testing set (n = 30) based on the date of surgery. We utilized a pre-trained AlexNet to extract deep learning features from seven different regions of the maximum transverse cross-section of tumors in various MRI sequence images. Subsequently, an extreme gradient boosting (XGBoost) classifier was employed to construct the MVI grade prediction model, with evaluation based on the area under the curve (AUC).

The XGBoost classifier trained with data from the 20-mm peritumoral region showed superior AUC compared to the tumor region alone. AUC values consistently increased when utilizing data from 5-mm, 10-mm, and 20-mm peritumoral regions. Combining arterial and delayed-phase data yielded the highest predictive performance, with micro- and macro-average AUCs of 0.78 and 0.74, respectively. Integration of clinical data further improved AUCs values to 0.83 and 0.80.

Compared with those of the tumor region, the deep learning features of the peritumoral region provide more important information for predicting the grade of MVI. Combining the tumor region and the 20-mm peritumoral region resulted in a relatively ideal and accurate region within which the grade of MVI can be predicted.

The 20-mm peritumoral region holds more significance than the tumor region in predicting MVI grade. Deep learning features can indirectly predict MVI by extracting information from the tumor region and directly capturing MVI information from the peritumoral region.

We investigated tumor and different peritumoral regions, as well as their fusion. MVI predominantly occurs in the peritumoral region, a superior predictor compared to the tumor region. The peritumoral 20 mm region is reasonable for accurately predicting the three-grade MVI.

Hepatocellular carcinoma (HCC) poses a significant threat due to its highly aggressive and high recurrence characteristics, necessitating urgent advances in diagnostic and therapeutic approaches. Long non-coding RNAs exert vital roles in HCC tumorigenesis, however the mechanisms of their expression regulation and functions are not fully elucidated yet. Herein, we identify that a novel tumor suppressor 'lnc-PIK3R1' was significantly downregulated in HCC tissues, which was correlated with poor prognosis. Functionally, lnc-PIK3R1 played tumor suppressor roles to inhibit the proliferation and mobility of HCC cells, and to impede the distant implantation of xenograft in mice. Mechanistic studies revealed that lnc-PIK3R1 interacted with miR-1286 and alleviated the repression on GSK3B by miR-1286. Notably, pharmacological inhibition of GSK3β compromised the tumor suppression effect by lnc-PIK3R1, confirming their functional relevance. Moreover, we identified that oncogenic YY1 acts as a specific transcriptional repressor to downregulate the expression of lnc-PIK3R1 in HCC. In summary, this study highlights the tumor-suppressive effect of lnc-PIK3R1, and provides new insights into the regulation of GSK3β expression in HCC, which would benefit the development of innovative intervention strategies for HCC.

Golgi protein 73 (GP73), a resident protein of the Golgi apparatus, is notably elevated in hepatocellular carcinoma (HCC). While its critical role in remodeling the tumor microenvironment (TME) is recognized, the intricate mechanisms are not fully understood. This study reveals that GP73 in HCC cells interacts with prolyl hydroxylase-2 (PHD-2) in a competitive manner, thereby impeding the hydroxylation of hypoxia-induced factor-1α (HIF-1α). The effect above promotes the production and secretion of vascular endothelial growth factor A (VEGFA). Moreover, exosomal GP73 derived from HCC cells can be internalized by human umbilical vein endothelial cells (HUVECs) and competitively interact with HECTD1, an E3 ubiquitin ligase targeting growth factor receptor-bound protein 2 (GRB2). This interaction stabilizes GRB2, thereby activating the Ras-mitogen-activated protein kinase (MAPK) signaling pathway. Consequently, escalated levels of GP73 intensify VEGF production in HCC cells and potentiate mitogenic signaling in vascular endothelial cells, fostering angiogenesis in the TME. Our findings propose that GP73 might serve as a novel target for anti-angiogenic therapy in HCC.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. As liver cancer often presents no noticeable symptoms in its early stages, most patients are diagnosed at an advanced stage, complicating treatment. Therefore, the identification of new biomarkers is crucial for the early detection and treatment of HCC. Research on exportin-5 (XPO5) could offer new avenues for early diagnosis and improve treatment strategies.

To explore the role of XPO5 in HCC progression and its potential as a prognostic biomarker.

This study assessed XPO5 mRNA expression in HCC using The Cancer Genome Atlas, TIMER, and International Cancer Genome Consortium databases, correlating it with clinical profiles and disease progression. We performed in vitro experiments to examine the effect of XPO5 on liver cell growth. Gene Set Enrichment Analysis, Kyoto Encyclopedia of Genes and Genomes, and Gene Ontology were used to elucidate the biological roles and signaling pathways. We also evaluated XPO5's impact on immune cell infiltration and validated its prognostic potential using machine learning.

XPO5 was significantly upregulated in HCC tissues, correlating with tumor grade, T-stage, and overall survival, indicating poor prognosis. Enrichment analyses linked high XPO5 expression with tumor immunity, particularly CD4 T cell memory activation and macrophage M0 infiltration. Drug sensitivity tests identified potential therapeutic agents such as MG-132, paclitaxel, and WH-4-023. Overexpression of XPO5 in HCC cells, compared to normal liver cells, was confirmed by western blotting and quantitative real-time polymerase chain reaction. The lentiviral transduction-mediated knockdown of XPO5 significantly reduced cell proliferation and metastasis. Among the various machine learning algorithms, the C5.0 decision tree algorithm achieved accuracy rates of 95.5% in the training set and 92.0% in the validation set.

Our analysis shows that XPO5 expression is a reliable prognostic indicator for patients with HCC and is significantly associated with immune cell infiltration.

Atezolizumab plus bevacizumab (ATE+BEV) therapy has become the recommended first-line therapy for patients with unresectable hepatocellular carcinoma (HCC) because of favorable treatment responses. However, there is a lack of data on sequential regimens after ATE+BEV treatment failure. We aimed to investigate the clinical outcomes of patients with advanced HCC who received subsequent systemic therapy for disease progression after ATE+BEV.

This multicenter, retrospective study included patients who started second-line systemic treatment with sorafenib or lenvatinib after HCC progressed on ATE+BEV between August 2019 and December 2022. Treatment response was assessed using the Response Evaluation Criteria in Solid Tumors (version 1.1.). Clinical features of the two groups were balanced through propensity score (PS) matching.

This study enrolled 126 patients, 40 (31.7%) in the lenvatinib group, and 86 (68.3%) in the sorafenib group. The median age was 63 years, and males were predominant (88.1%). In PS-matched cohorts (36 patients in each group), the objective response rate was similar between the lenvatinib- and sorafenib-treated groups (5.6% vs. 8.3%; P=0.643), but the disease control rate was superior in the lenvatinib group (66.7% vs. 22.2%; P<0.001). Despite the superior progression- free survival (PFS) in the lenvatinib group (3.5 vs. 1.8 months, P=0.001), the overall survival (OS, 10.3 vs. 7.5 months, P=0.353) did not differ between the two PS-matched treatment groups.

In second-line therapy for unresectable HCC after ATE+BEV failure, lenvatinib showed better PFS and comparable OS to sorafenib in a real-world setting. Future studies with larger sample sizes and longer follow-ups are needed to optimize second-line treatment.

Exosomes, also termed extracellular vesicles (EVs), are an important component of the tumor microenvironment (TME) and exert versatile effects on the molecular communications in the TME of hepatocellular carcinoma (HCC). Exosome-mediated intercellular communication is closely associated with the tumorigenesis and development of HCC. Exosomes can be extracted through ultracentrifugation and size exclusion, followed by molecular analysis through sequencing. Increasing studies have confirmed the important roles of exosome-derived ncRNAs in HCC, including tumorigenesis, progression, immune escape, and treatment resistance. Due to the protective membrane structure of exosomes, the ncRNAs carried by exosomes can evade degradation by enzymes in body fluids and maintain good expression stability. Thus, exosome-derived ncRNAs are highly suitable as biomarkers for the diagnosis and prognostic prediction of HCC, such as exosomal miR-21-5p, miR-221-3p and lncRNA-ATB. In addition, substantial studies revealed that the up-or down-regulation of exosome-derived ncRNAs had an important impact on HCC progression and response to treatment. Exosomal biomarkers, such as miR-23a, lncRNA DLX6-AS1, miR-21-5p, lncRNA TUC339, lncRNA HMMR-AS1 and hsa_circ_0004658, can reshape immune microenvironment by regulating M2-type macrophage polarization and then promote HCC development. Therefore, by controlling exosome biogenesis and modulating exosomal ncRNA levels, HCC may be inhibited or eliminated. In this current review, we summarized the recent findings on the role of exosomes in HCC progression and analyzed the relationship between exosome-derived ncRNAs and HCC diagnosis and treatment.

Hepatocellular carcinoma (HCC) is among the most common malignancies worldwide and is characterized by high rates of morbidity and mortality, posing a serious threat to human health. Interventional embolization therapy is the main treatment against middle- and late-stage liver cancer, but its efficacy is limited by the performance of embolism, hence the new embolic materials have provided hope to the inoperable patients. Especially, hydrogel materials with high embolization strength, appropriate viscosity, reliable security and multifunctionality are widely used as embolic materials, and can improve the efficacy of interventional therapy. In this review, we have described the status of research on hydrogels and challenges in the field of HCC therapy. First, various preparation methods of hydrogels through different cross-linking methods are introduced, then the functions of hydrogels related to HCC are summarized, including different HCC therapies, various imaging techniques, in vitro 3D models, and the shortcomings and prospects of the proposed applications are discussed in relation to HCC. We hope that this review is informative for readers interested in multifunctional hydrogels and will help researchers develop more novel embolic materials for interventional therapy of HCC.

The safety of laparoscopic hepatectomy for inherited coagulation disorders is unclear; however, the safety of open hepatectomy has been reported in several studies. Herein, we report the first case of a laparoscopic hepatectomy for a patient with von Willebrand Disease (VWD).

A 76-year-old male with a history of chronic hepatitis C and VWD type 2B was advised surgical resection of a 4 cm hepatocellular carcinoma in segment 7 of the liver. The patient was diagnosed with VWD in his 40 s due to gastrointestinal bleeding caused by gastric erosion. The von Willebrand factor (VWF) ristocetin cofactor activity was 30%, and VWF large multimer deficiency and increased ristocetin-induced platelet agglutination were observed. The preoperative platelet count was reduced to 3.5 × 104/μL; however, preoperative imaging findings had no evidence of liver cirrhosis, such as any collateral formations and splenomegaly. The indocyanine green retention rate at 15 min was 10%, and his Child-Pugh score was 5 (classification A). Perioperatively, VWF/factor VIII was administered in accordance with our institutional protocol. A laparoscopic partial hepatectomy of the right posterior segment was performed. The most bleeding during surgery occurred during the mobilization of the right lobe of the liver due to inflammatory adhesion between the retroperitoneum and the tumor. Bleeding during parenchymal transection was controlable. The duration of hepatic inflow occlusion was 65 min. The surgical duration was 349 min, and the estimated blood loss was 2150 ml. Four units of red blood cells and fresh frozen plasma were transfused at the initiation of parenchymal transection, and 10 units of platelets were transfused at the end of the parenchymal transection. On postoperative day 1, the transection surface drainage fluid became hemorrhagic, and emergency contrast-enhanced computed tomography showed extravasation in the greater omentum. Percutaneous transcatheter arterial embolization of the omental branch of the right gastroepiploic artery was performed. No further postoperative interventions were required. The patient was discharged on postoperative day 14.

The indications for laparoscopic hepatectomy in patients with VWD should be carefully considered, and an open approach may still be the standard approach for patients with VWD.

Abnormalities in epigenetic modifications can cause malignant transformations in cells, leading to cancers of the gastrointestinal (GI) tract, which accounts for 20% of all cancers worldwide. Among the epigenetic alterations, DNA hypomethylation is associated with genomic instability. In addition, CpG methylation and promoter hypermethylation have been recognized as biomarkers for different malignancies. In GI cancers, epigenetic alterations affect genes responsible for cell cycle control, DNA repair, apoptosis, and tumorigenic-specific signaling pathways. Understanding the pattern of alterations in DNA methylation in GI cancers could help scientists discover new molecular-based pharmaceutical treatments. This study highlights alterations in DNA methylation in GI cancers. Understanding epigenetic differences among GI cancers may improve targeted therapies and lead to the discovery of new diagnostic biomarkers.

Six Transmembrane Epithelial Antigen of Prostate 2 (STEAP2) belongs to a family of metalloreductases, which indirectly aid in uptake of iron and copper ions. Its role in hepatocellular carcinoma (HCC) remains to be characterized. Here, we report that STEAP2 expression was upregulated in HCC tumors compared with paired adjacent non-tumor tissues by RNA sequencing, RT-qPCR, Western blotting, and immunostaining. Public HCC datasets demonstrated upregulated STEAP2 expression in HCC and positive association with tumor grade. Transient and stable knockdown (KD) of STEAP2 in HCC cell lines abrogated their malignant phenotypes in vitro and in vivo, while STEAP2 overexpression showed opposite effects. STEAP2 KD in HCC cells led to significant alteration of genes associated with extracellular matrix organization, cell adhesion/chemotaxis, negative enrichment of an invasiveness signature gene set, and inhibition of cell migration/invasion. STEAP2 KD reduced intracellular copper levels and activation of stress-activated MAP kinases including p38 and JNK. Treatment with copper rescued the reduced HCC cell migration due to STEAP2 KD and activated p38 and JNK. Furthermore, treatment with p38 or JNK inhibitors significantly inhibited copper-mediated cell migration. Thus, STEAP2 plays a malignant-promoting role in HCC cells by driving migration/invasion via increased copper levels and MAP kinase activities. Our study uncovered a novel molecular mechanism contributing to HCC malignancy and a potential therapeutic target for HCC treatment.

This study aimed to examine the role of long non-coding RNA PCED1B antisense RNA 1 (PCED1B-AS1) in the development of hepatocellular carcinoma (HCC).

A total of 62 pairs of HCC tissues and adjacent non-tumor tissues were obtained from 62 HCC patients. The interactions of PCED1B-AS1 and microRNA-34a (miR-34a) were detected by dual luciferase activity assay and RNA pull-down assay. The RNA expression levels of PCED1B-AS1, miR-34a and CD44 were detected by RT-qPCR, and the protein expression level of CD44 was determined by Western blotting. The cell proliferation was detected by cell proliferation assay, and the cell invasion and migration by transwell invasion assay. The HCC tumor growth after PCED1B-AS1 was downregulated was determined by in vivo animal study.

PCED1B-AS1 was highly expressed in HCC tissues, which was associated with poor survival of HCC patients. Furthermore, PCED1B-AS1 interacted with miR-34a in HCC cells, but they did not regulate the expression of each other. Additionally, PCED1B-AS1 increased the expression level of CD44, which was targeted by miR-34a. The cell proliferation and invasion assay revealed that miR-34a inhibited the proliferation and invasion of HCC in vitro, while CD44 exhibited the opposite effects. Furthermore, PCED1B-AS1 suppressed the role of miR-34a. Moreover, the knockdown of PCED1B-AS1 repressed the HCC tumor growth in nude mice in vivo.

PCED1B-AS1 may play an oncogenic role by regulating the miR-34a/CD44 axis in HCC.

Liver cirrhosis is the largest risk factor for developing hepatocellular carcinoma (HCC), and surveillance is therefore recommended among this population. Current guidance recommends surveillance with ultrasound, with or without alpha-fetoprotein (AFP). This review is part of a larger project looking at benefits, harms and costs of surveillance for HCC in people with cirrhosis. It aims to synthesise the evidence on the diagnostic accuracy of imaging or biomarker tests, alone or in combination, to identify HCC in adults with liver cirrhosis in a surveillance programme.

We will identify studies through a 2021 Cochrane review with similar eligibility criteria, and a database search of MEDLINE, Embase and the Cochrane Database of Systematic Reviews. We will include diagnostic test accuracy studies with adult cirrhosis patients of any aetiology. Studies must assess at least one of the following index tests: ultrasound (US), magnetic resonance imaging (MRI), computerised tomography (CT), alpha-fetoprotein (AFP), des-gamma-carboxyprothrombin (DCP), lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), a genomic biomarker, or a diagnostic prediction model incorporating at least one of the above-mentioned tests. We will assess studies for risk of bias using QUADAS-2 and QUADAS-C. We will combine data using bivariate random effects meta-analyses. For tests evaluated across varying diagnostic thresholds, we will produce pooled estimates of sensitivity and specificity across the full range of numerical thresholds, where possible. Where sufficient studies compare two or more index tests, we will perform additional analyses to compare the accuracy of different tests. Where feasible, we will stratify all meta-analyses by tumour size and patient characteristics, including cirrhosis aetiology and liver disease severity.

This review will synthesise evidence across the full range of possible surveillance tests, using advanced statistical methods to summarise accuracy across all thresholds and to compare the accuracy of different tests.

CRD42022357163.

The heterogeneity of Hepatocellular Carcinoma (HCC) poses a barrier to effective treatment. Stratifying highly heterogeneous HCC into molecular subtypes with similar features is crucial for personalized anti-tumor therapies. Although driver genes play pivotal roles in cancer progression, their potential in HCC subtyping has been largely overlooked. This study aims to utilize driver genes to construct HCC subtype models and unravel their molecular mechanisms. Utilizing a novel computational framework, we expanded the initially identified 96 driver genes to 1192 based on mutational aspects and an additional 233 considering driver dysregulation. These genes were subsequently employed as stratification markers for further analyses. A novel multi-omics subtype classification algorithm was developed, leveraging mutation and expression data of the identified stratification genes. This algorithm successfully categorized HCC into two distinct subtypes, CLASS A and CLASS B, demonstrating significant differences in survival outcomes. Integrating multi-omics and single-cell data unveiled substantial distinctions between these subtypes regarding transcriptomics, mutations, copy number variations, and epigenomics. Moreover, our prognostic model exhibited excellent predictive performance in training and external validation cohorts. Finally, a 10-gene classification model for these subtypes identified TTK as a promising therapeutic target with robust classification capabilities. This comprehensive study provides a novel perspective on HCC stratification, offering crucial insights for a deeper understanding of its pathogenesis and the development of promising treatment strategies.

Conventional x-ray imaging and fluoroscopy have limitations in quantitation due to several challenges, including scatter, beam hardening, and overlapping tissues. Dual-energy (DE) imaging, with its capability to quantify area density of specific materials, is well-suited to address such limitations, but only if the dual-energy projections are acquired with perfect spatial and temporal alignment and corrected for scatter.

In this work, we propose single-shot quantitative imaging (SSQI) by combining the use of a primary modulator (PM) and dual-layer (DL) detector, which enables motion-free DE imaging with scatter correction in a single exposure.

The key components of our SSQI setup include a PM and DL detector, where the former enables scatter correction for the latter while the latter enables beam hardening correction for the former. The SSQI algorithm allows simultaneous recovery of two material-specific images and two scatter images using four sub-measurements from the PM encoding. The concept was first demonstrated using simulation of chest x-ray imaging for a COVID patient. For validation, we set up SSQI geometry on our tabletop system and imaged acrylic and copper slabs with known thicknesses (acrylic: 0-22.5 cm; copper: 0-0.9 mm), estimated scatter with our SSQI algorithm, and compared the material decomposition (MD) for different combinations of the two materials with ground truth. Second, we imaged an anthropomorphic chest phantom containing contrast in the coronary arteries and compared the MD with and without SSQI. Lastly, to evaluate SSQI in dynamic applications, we constructed a flow phantom that enabled dynamic imaging of iodine contrast.

Our simulation study demonstrated that SSQI led to accurate scatter correction and MD, particularly for smaller focal blur and finer PM pitch. In the validation study, we found that the root mean squared error (RMSE) of SSQI estimation was 0.13 cm for acrylic and 0.04 mm for copper. For the anthropomorphic phantom, direct MD resulted in incorrect interpretation of contrast and soft tissue, while SSQI successfully distinguished them quantitatively, reducing RMSE in material-specific images by 38%-92%. For the flow phantom, SSQI was able to perform accurate dynamic quantitative imaging, separating contrast from the background.

We demonstrated the potential of SSQI for robust quantitative x-ray imaging. The integration of SSQI is straightforward with the addition of a PM and upgrade to a DL detector, which may enable its widespread adoption, including in techniques such as radiography and dynamic imaging (i.e., real-time image guidance and cone-beam CT).

Long non-coding RNAs (LncRNAs) have been found to be a potential prognostic factor for cancers, including hepatocellular carcinoma (HCC). Some LncRNAs have been confirmed as potential indicators to quantify genomic instability (GI). Nevertheless, GI-LncRNAs remain largely unexplored. This study established a GI-derived LncRNA signature (GILncSig) that can predict the prognosis of HCC patients.

To establish a GILncSig that can predict the prognosis of HCC patients.

Identification of GI-LncRNAs was conducted by combining LncRNA expression and somatic mutation profiles. The GI-LncRNAs were then analyzed for functional enrichment. The GILncSig was established in the training set by Cox regression analysis, and its predictive ability was verified in the testing set and TCGA set. In addition, we explored the effects of the GILncSig and TP53 on prognosis.

A total of 88 GI-LncRNAs were found, and functional enrichment analysis showed that their functions were mainly involved in small molecule metabolism and GI. The GILncSig was constructed by 5 LncRNAs (miR210HG, AC016735.1, AC116351.1, AC010643.1, LUCAT1). In the training set, the prognosis of high-risk patients was significantly worse than that of low-risk patients, and similar results were verified in the testing set and TCGA set. Multivariate Cox regression analysis and stratified analysis confirmed that the GILncSig could be used as an independent prognostic factor. Receiver operating characteristic curve analysis of the GILncSig showed that the area under the curve (0.773) was higher than the two LncRNA signatures published recently. Furthermore, the GILncSig may have a better predictive performance than TP53 mutation status alone.

We established a GILncSig that can predict the prognosis of HCC patients, which will help to guide prognostic evaluation and treatment decisions.