Liver Cancer Patients Research Articles

In Vitro Simulated Ketogenic Diet Inhibits the Proliferation and Migration of Liver Cancer Cells by Reducing Insulin Production and Down-regulating FOXC2 Expression.

Ketogenic diet (KD) may benefit patients with liver cancer, but the underlying mechanism of its anti-cancer effect remains an open issue. This work aimed to explore the influence of simulated KD on the proliferation and migration of cultured hepatoma cells. The low-glucose medium supplemented with β-hydroxybutyrate (BHB-Glow) was utilized to simulate clinical KD treatment. Western blot was utilized for detecting the expression of glycolysis-related proteins, Seahorse XF96 for oxygen consumption rate (OCR) and extracellular acidification rate (ECAR), and ELISA for insulin content. Expression of FOXC2 in liver cancer cells was analyzed by bioinformatics and qPCR. Cell Count Kit-8 (CCK-8) testing kit was utilized for testing cell viability. KD treatment significantly reduced the expression of glycolysis-related proteins in Huh-7 cells, inhibited insulin production in β islet cells, reduced ECAR, and increased OCR. FOXC2 was significantly up-regulated in Huh-7 cell line, and sh-FOXC2 hindered the proliferation and migration of Huh-7 cells. The exogenous addition of insulin promoted the malignant progression of Huh-7 cells. Together, the medium simulating KD environment strengthened the protection of liver cancer cells by reducing insulin production and down-regulating FOXC2 expression. This study confirmed through in vitro cell experiments that KD could inhibit the proliferation and migration of liver cancer cells by targeting down regulation of insulin and FOXC2 expression, providing new theoretical basis for the treatment of liver cancer patients.

1034P Preclinical development of genetically modified tumor-infiltrating lymphocytes using biopsy samples from liver cancer patients

1034P Preclinical development of genetically modified tumor-infiltrating lymphocytes using biopsy samples from liver cancer patients

FOXM1 Upregulates O-GlcNAcylation Level Via The Hexosamine Biosynthesis Pathway to Promote Angiogenesis in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) presents significant challenges in treatment and prognosis because of its aggressive nature and high metastatic potential. This study aims to investigate the role of the hexosamine biosynthesis pathway (HBP) and its association with HCC progression and prognosis. We identified SPP1 and FOXM1 as hub genes within the HBP pathway, showing their correlation with poor prognosis and late-stage progression. In addition, the analysis uncovered the complex participation of the HBP pathway in nutrients and oxygen reactions, PI3K-AKT signaling, AMPK activation, and angiogenesis regulation. The disruption of these pathways is pivotal in influencing the growth and progression of HCC. Targeting the HBP presents a promising therapeutic approach to modulate the tumor microenvironment, thereby enhancing the efficacy of immunotherapy. In addition, FOXM1 was identified as the HBP pathway regulator, influencing cellular O-GlcNAcylation level and VEGF secretion, thereby promoting angiogenesis in HCC. Inhibition of O-GlcNAcylation significantly hindered angiogenesis, which is suggested as a potential avenue for therapeutic intervention. Our research demonstrates the practicality of using the HBP-related gene as a prognostic marker in liver cancer patients and suggests targeting FOXM1 as a novel avenue for personalized therapy.

GLYAT suppresses liver cancer and clear cell renal cell carcinoma progression by downregulating ROCK1 expression.

The liver and kidney are important metabolic organs in the body and common sites of tumor occurrence. Glycine-N-acyltransferase (GLYAT) is primarily expressed in the liver and kidney and downregulated in several tumors. But its specific functions and molecular mechanisms in liver cancer and clear cell renal cell carcinoma (ccRCC) have not yet been fully elucidated. The aim of this study was to explore the role and clinical significance of GLYAT in liver cancer and ccRCC. This study used proteomics technology to identify differentially expressed proteins in liver cancer. Western blot and immunohistochemistry (IHC) were used to analyze the protein expression pattern of GLYAT. assays were performed in liver cancer and ccRCC cells. Xenograft models in nude mice were used to confirm the roles of GLYAT in liver cancer. Moreover, the downstream regulatory proteins of GLYAT were identified by proteomics. GLYAT was lowly expressed in liver cancer and ccRCC. Immunofluorescence staining indicated that GLYAT was mainly expressed in the cytoplasm, particularly the mitochondria. Kaplan-Meier curves showed that the low protein expression of GLYAT was correlated with a poor prognosis in liver cancer and ccRCC patients. Moreover, GLYAT expression was associated with several clinical parameters in liver cancer. Cell experiments showed that the overexpression of GLYAT inhibited cell proliferation and migration abilities; however, interfering GLYAT protein expression rescued these abilities in GLYAT overexpression (GLYAT-OE) cells. In vivo assays confirmed the tumor-suppressor function of GLYAT in liver cancer. Moreover, our research showed that GLYAT downregulated Rho-associated coiled-coil-containing protein kinase 1 (ROCK1). Our study showed that GLYAT is lowly expressed in liver cancer and ccRCC, emphasizing its prognostic significance. It also showed that GLYAT inhibits the progression of liver cancer and ccRCC by downregulating ROCK1.

LUBAC enables tumor-promoting LTβ receptor signaling by activating canonical NF-κB.

Lymphotoxin β receptor (LTβR), a member of the TNF receptor superfamily (TNFR-SF), is essential for development and maturation of lymphoid organs. In addition, LTβR activation promotes carcinogenesis by inducing a proinflammatory secretome. Yet, we currently lack a detailed understanding of LTβR signaling. In this study we discovered the linear ubiquitin chain assembly complex (LUBAC) as a previously unrecognized and functionally crucial component of the native LTβR signaling complex (LTβR-SC). Mechanistically, LUBAC-generated linear ubiquitin chains enable recruitment of NEMO, OPTN and A20 to the LTβR-SC, where they act coordinately to regulate the balance between canonical and non-canonical NF-κB pathways. Thus, different from death receptor signaling, where LUBAC prevents inflammation through inhibition of cell death, in LTβR signaling LUBAC is required for inflammatory signaling by enabling canonical and interfering with non-canonical NF-κB activation. This results in a LUBAC-dependent LTβR-driven inflammatory, protumorigenic secretome. Intriguingly, in liver cancer patients with high LTβR expression, high expression of LUBAC correlates with poor prognosis, providing clinical relevance for LUBAC-mediated inflammatory LTβR signaling.

Identification of SPP1+ macrophages in promoting cancer stemness via vitronectin and CCL15 signals crosstalk in liver cancer

Macrophages play a multifaceted role in cancer biology, with both pro-tumorigenic and anti-tumorigenic functions. Understanding the mechanisms underlying macrophage involvement in cancer progression is essential for the development of therapeutic strategies. Our study analyzed single-cell RNA sequencing data from 12 patients with liver cancer and identified a subpopulation of macrophages characterized by elevated expression of SPP1, which correlates with poor prognosis in liver cancer patients. These SPP1+ macrophages induce upregulation of tumor stemness through a vitronectin (VTN)-dependent paracrine mechanism. Mechanistically, VTN derived from SPP1+ macrophages promote integrin αvβ5/adenosine 5‘-monophosphate-activated protein kinase (AMPK)/Yes-associated protein 1 (YAP1)/SYR-box transcription factor 4 (SOX4) signaling, mediating liver tumor stemness and progression. Conversely, CCL15 produced by liver cancer cells drives polarization of M0 macrophages toward an SPP1+ macrophage phenotype, establishing a positive feedback loop of macrophage-tumor stemness. Furthermore, the presence of SPP1+ macrophages confers chemoresistance in liver cancer, and inhibition of the macrophage-tumor feedback loop through targeting integrin αvβ5/YAP1 signaling sensitizes liver cancer cells to chemotherapy. Our study highlights the crucial role of SPP1+ macrophages in liver cancer progression, providing novel insights for clinical liver cancer therapy.

ENG is a Biomarker of Prognosis and Angiogenesis in Liver Cancer, and Promotes the Differentiation of Tumor Cells into Vascular ECs

Background: Liver cancer is a highly lethal malignancy with frequent recurrence, widespread metastasis, and low survival rates. The aim of this study was to explore the role of Endoglin (ENG) in liver cancer progression, as well as its impacts on angiogenesis, immune cell infiltration, and the therapeutic efficacy of sorafenib. Methods: A comprehensive evaluation was conducted using online databases Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA), 76 pairs of clinical specimens of tumor and adjacent non-tumor liver tissue, and tissue samples from 32 hepatocellular carcinoma (HCC) patients treated with sorafenib. ENG expression levels were evaluated using quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR), Western blot, and immunohistochemical analysis. Cox regression analysis, Spearman rank correlation analysis, and survival analysis were used to assess the results. Functional experiments included Transwell migration assays and tube formation assays with Human Umbilical Vein Endothelial Cells (HUVECs). Results: Tumor cells exhibited retro-differentiation into endothelial-like cells, with a significant increase in ENG expression in these tumor-derived endothelial cells (TDECs). High expression of ENG was associated with more aggressive cancer characteristics and worse patient prognosis. Pathway enrichment and functional analyses identified ENG as a key regulator of immune responses and angiogenesis in liver cancer. Further studies confirmed that ENG increases the expression of Collagen type Iα1 (COL1A1), thereby promoting angiogenesis in liver cancer. Additionally, HCC patients with elevated ENG levels responded well to sorafenib treatment. Conclusions: This study found that ENG is an important biomarker of prognosis in liver cancer. Moreover, ENG is associated with endothelial cell differentiation in liver cancer and plays a crucial role in formation of the tumor vasculature. The assessment of ENG expression could be a promising strategy to identify liver cancer patients who might benefit from targeted immunotherapies.

Resolution of Optimal Mitochondrial and Nuclear DNA Enrichment in Target-Panel Sequencing and Physiological Mitochondrial DNA Copy Number Estimation in Liver Cancer and Non-Liver Cancer Subjects.

Mitochondria generate energy to support cells. They are important organelles that engage in key biological pathways. The dysfunction of mitochondria can be linked to hepatocarcinogenesis, which has been actively explored in recent years. To investigate the mitochondrial dysfunction caused by genetic variations, target-panel sequencing is a flexible and promising strategy. However, the copy number of mitochondria generally exceeds nuclear DNA, which raises a concern that uneven target enrichment of mitochondrial DNA (mtDNA) and nuclear DNA (ncDNA) in target-panel sequencing would lead to an undesirably biased representation of them. To resolve this issue, we evaluated the optimal pooling of mtDNA probes and ncDNA probes by a series of dilutions of mtDNA probes in both genomic DNA (gDNA) and cell-free DNA (cfDNA) samples. The evaluation was based on read count, average sequencing depth and coverage of targeted regions. We determined that an mtDNA:ncDNA probe ratio of around 1:10 would offer a good balance of sequencing performance and cost effectiveness. Moreover, we estimated the median physiological mtDNA:ncDNA copy ratio as 38.1 and 2.9 in cfDNA and gDNA samples of non-liver cancer subjects, respectively, whereas they were 20.0 and 2.1 in the liver cancer patients. Taken together, this study revealed the appropriate pooling strategy of mtDNA probes and ncDNA probes in target-panel sequencing and suggested the normal range of physiological variation of the mtDNA:ncDNA copy ratio in non-liver cancer individuals. This can serve as a useful reference for future target-panel sequencing investigations of the mitochondrial genome in liver cancer.

Advancements in nutritional diagnosis and support strategies during the perioperative period for patients with liver cancer.

Liver cancer represents a grave hepatic condition and constitutes a significant global health concern. Surgical resection remains the principal therapeutic modality for liver cancer. Nevertheless, perioperative malnutrition exerts a notable impact on patients with liver cancer, emerging as an independent risk factor for disease mortality and adverse outcomes. Hence, precise nutritional diagnosis and timely nutritional support hold the potential to enhance therapeutic efficacy and quality of life for liver cancer patients. This study represents a meticulous foray into the literature, extracting data from PubMed, Web of Science, and EMBASE databases, with a focus on the past 5 years. It scrutinizes the impact of malnutrition on patients undergoing liver cancer surgery, the etiological underpinnings of malnutrition within this patient cohort, the critical assessment of perioperative nutritional status, and the strategic approaches to nutritional support. Utilizing rigorous inclusion and exclusion criteria, the amassed scholarly works are meticulously synthesized, methodically organized, and categorically elaborated upon. Ultimately, the authors propose the incorporation of a multidisciplinary nutrition management team during the perioperative period, comprising nutritionists, pharmacists, physicians, nurses, psychologists, and rehabilitation therapists, among other specialized professionals. Together, they collaborate to devise and implement personalized nutritional support plans, monitor patients' nutritional status, and make necessary adjustments as required. Through comprehensive management and intervention, improvements in the nutritional status of liver cancer patients can be achieved, thereby enhancing surgical success rates and facilitating postoperative recovery. It is believed that this manuscript will offer valuable insights to advance the nutritional management during the perioperative phase of liver cancer, aiding in ameliorating patients' nutritional status and treatment outcomes.

Assessing TGF-β Prognostic Model Predictions for Chemotherapy Response and Oncogenic Role of FKBP1A in Liver Cancer.

The Transforming Growth Factor-Beta (TGF-β) signaling pathway plays a crucial role in the pathogenesis of diseases. This study aimed to identify differentially expressed TGF-β-related genes in liver cancer patients and to correlate these findings with clinical features and immune signatures. The TCGA-STAD and LIRI-JP cohorts were utilized for a comprehensive analysis of TGF-β- related genes. Differential gene expression, functional enrichment, survival analysis, and machine learning techniques were employed to develop a prognostic model based on a TGF-β-related gene signature (TGFBRS). We developed a prognostic model for liver cancer based on the expression levels of nine TGF-β- related genes. The model indicates that higher TGFBRS values are associated with poorer prognosis, higher tumor grades, more advanced pathological stages, and resistance to chemotherapy. Additionally, the TGFBRS-High subtype was characterized by elevated levels of immune-suppressive cells and increased expression of immune checkpoint molecules. Using a Gradient Boosting Decision Tree (GBDT) machine learning approach, the FKBP1A gene was identified as playing a significant role in liver cancer. Notably, knocking down FKBP1A significantly inhibited the proliferation and metastatic capabilities of liver cancer cells both in vitro and in vivo. Our study highlights the potential of TGFBRS in predicting chemotherapy responses and in shaping the tumor immune microenvironment in liver cancer. The results identify FKBP1A as a promising molecular target for developing preventive and therapeutic strategies against liver cancer. Our findings could potentially guide personalized treatment strategies to improve the prognosis of liver cancer patients.

Independent risk factor of drug eruption in immune checkpoint inhibitors treated liver cancer patients: high systemic immune-inflammation index

Purpose The clinical application of immune checkpoint inhibitors (ICIs) has significantly improved the prognosis of liver cancer patients. However, drug eruption associated with ICI monotherapy or combination therapy not only impacts the quality of life and treatment progress of liver cancer patients but also poses a potential threat to their lives. The study aims to investigate the risk factors of drug eruption in liver cancer patients undergoing ICIs in real-world settings. Methods We retrospectively collected data from liver cancer patients who underwent ICI therapies at the Third Affiliated Hospital of Sun Yat-sen University between 2021 and 2022. A propensity score matching (PSM) method was employed to match 31 liver cancer patients with ICI-related drug eruption (drug eruption group) to 228 liver cancer patients without immune-related adverse reactions (control group) in a 1:2 ratio, creating two groups of patients with comparable baseline characteristics. Subsequently, logistic regression analysis was then conducted to analyze the clinical risk factors associated with drug eruption caused by ICIs. Results Before PSM, there were statistically significant differences between the drug eruption group (31 cases) and the control group (228 cases) in two variables: Child-Pugh liver function classification and presence of vascular invasion (both p < 0.05). However, after PSM, no statistically significant differences were found in the clinical variables between the drug eruption group (28 cases) and the control group (52 cases). Univariate analysis revealed significantly higher levels of aspartate amino­transferase, alanine aminotransferase, glutamyl transpeptidase, and systemic immune-inflammation index (SII) and a significantly lower rate of liver cancer resection surgery before immunotherapy in liver cancer patients with drug eruption compared to the control group (p < 0.05). Multivariate analysis indicated that an elevated SII level before immunotherapy was significantly associated with the occurrence of drug eruption in liver cancer patients treated with ICIs (p < 0.05). The predictive performance of SII before immunotherapy in liver cancer patients for ICI-related drug eruption yielded an area under the receiver operator characteristic curve of 0.852, with a critical value of 749.189. Sensitivity and specificity were determined as 85.7% and 75%, respectively (p < 0.05). Conclusions Elevated systemic immune-inflammation index is identified as a risk factor for drug eruption occurrence in liver cancer patients treated with ICI therapies.

DRD4 promotes chemo-resistance and cancer stem cell-like phenotypes by mediating the activation of the Akt/β-catenin signaling axis in liver cancer.

Liver cancer stem cells (LCSCs) significantly impact chemo-resistance and recurrence in liver cancer. Dopamine receptor D4 (DRD4) is known to enhance the cancer stem cell (CSC) phenotype in glioblastoma and correlates with poor prognosis in some non-central nervous system tumors; however, its influence on LCSCs remains uncertain. To investigate the gene and protein expression profiles of DRD4 in LCSCs and non-LCSCs, we utilized transcriptome sequencing and Western blotting analysis. Bioinformatics analysis and immunohistochemistry were employed to assess the correlation between DRD4 expression levels and the pathological characteristics of liver cancer patients. The impact of DRD4 on LCSC phenotypes and signaling pathways were explored using pharmacological or gene-editing techniques. Additionally, the effect of DRD4 on the protein expression and intracellular localization of β-catenin were examined using Western blotting and immunofluorescence. DRD4 expression is significantly elevated in LCSCs and correlates with short survival in liver cancer. The expression and activity of DRD4 are positive to resistance, self renewal and tumorigenicity in HCC. Mechanistically, DRD4 stabilizes β-catenin and promotes its entry into the nucleus via activating the PI3K/Akt/GSK-3β pathway, thereby enhancing LCSC phenotypes. Inhibiting DRD4 expression and activation offers a promising targeted therapy for eradicating LCSCs and relieve chemo-resistance.

FA-Net: A hierarchical feature fusion and interactive attention-based network for dose prediction in liver cancer patients

Dose prediction is a crucial step in automated radiotherapy planning for liver cancer. Several deep learning-based approaches for dose prediction have been proposed to enhance the design efficiency and quality of radiotherapy plan. However, these approaches usually take CT images and contours of organs at risk (OARs) and planning target volume (PTV) as a multi-channel input and is thus difficult to extract sufficient feature information from each input, which results in unsatisfactory dose distribution. In this paper, we propose a novel dose prediction network for liver cancer based on hierarchical feature fusion and interactive attention. A feature extraction module is first constructed to extract multi-scale features from different inputs, and a hierarchical feature fusion module is then built to fuse these multi-scale features hierarchically. A decoder based on attention mechanism is designed to gradually reconstruct the fused features into dose distribution. Additionally, we design an autoencoder network to generate a perceptual loss during training stage, which is used to improve the accuracy of dose prediction. The proposed method is tested on private clinical dataset and obtains HI and CI of 0.31 and 0.87, respectively. The experimental results are better than those by several existing methods, indicating that the dose distribution generated by the proposed method is close to that approved in clinics. The codes are available at https://github.com/hired-ld/FA-Net.

Percutaneous Delivery of Oncogel for Targeted Liver Tumor Ablation and Controlled Release of Therapeutics.

Advanced-stage liver cancers are associated with poor prognosis and have limited treatment options, often leading the patient to hospice care. Percutaneous intratumoral injection of anticancer agents has emerged as a potential alternative to systemic therapy to overcome tumor barriers, increase bioavailability, potentiate immunotherapy, and avoid systemic toxicity, which advanced-stage cancer patients cannot tolerate. Here, an injectable OncoGel (OG) comprising of a nanocomposite hydrogel loaded with an ionic liquid (IL) is developed for achieving a predictable and uniform tumor ablation and long-term slow release of anticancer agents into the ablation zone. Rigorous mechanical, physiochemical, drug release, cytotoxicity experiments, and ex vivo human tissue testing identify an injectable version of the OG with bactericidal properties against highly resistant bacteria. Intratumoral injection of OG loaded with Nivolumab (Nivo) and doxorubicin (Dox) into highly malignant tumor models in mice, rats, and rabbits demonstrates enhanced survival and tumor regression associated with robust tissue ablation and drug distribution throughout the tumor. Mass cytometry and proteomic studies in a mouse model of colorectal cancer that often metastasizes to the liver indicate an enhanced anticancer immune response following the intratumoral injection of OG. OG may augment immunotherapy and potentially improve outcomes in liver cancer patients.

Spatial multiomics reveals a subpopulation of fibroblasts associated with cancer stemness in human hepatocellular carcinoma

BackgroundCancer-associated fibroblasts (CAFs) are the prominent cell type in the tumor microenvironment (TME), and CAF subsets have been identified in various tumors. However, how CAFs spatially coordinate other cell populations within the liver TME to promote cancer progression remains unclear.MethodsWe combined multi-region proteomics (6 patients, 24 samples), 10X Genomics Visium spatial transcriptomics (11 patients, 25 samples), and multiplexed imaging (92 patients, 264 samples) technologies to decipher the expression heterogeneity, functional diversity, spatial distribution, colocalization, and interaction of fibroblasts. The newly identified CAF subpopulation was validated by cells isolated from 5 liver cancer patients and in vitro functional assays.ResultsWe identified a liver CAF subpopulation, marked by the expression of COL1A2, COL4A1, COL4A2, CTGF, and FSTL1, and named F5-CAF. F5-CAF is preferentially located within and around tumor nests and colocalizes with cancer cells with higher stemness in hepatocellular carcinoma (HCC). Multiplexed staining of 92 patients and the bulk transcriptome of 371 patients demonstrated that the abundance of F5-CAFs in HCC was associated with a worse prognosis. Further in vitro experiments showed that F5-CAFs isolated from liver cancer patients can promote the proliferation and stemness of HCC cells.ConclusionsWe identified a CAF subpopulation F5-CAF in liver cancer, which is associated with cancer stemness and unfavorable prognosis. Our results provide potential mechanisms by which the CAF subset in the TME promotes the development of liver cancer by supporting the survival of cancer stem cells.

Symptom clusters and network analysis of patients with intermediate and advanced liver cancer treated with targeted immunotherapy.

This study aims to identify symptom clusters in patients with intermediate and advanced liver cancer receiving targeted immunotherapy, focusing on core and bridge symptoms to establish a foundation for precise symptom management. This study used a cross-sectional survey and utilized convenience sampling from May 2023 to January 2024 at a third-class hospital in Shanghai, China. The severity of symptoms in liver cancer patients during treatment was evaluated using the Memorial Symptom Assessment Scale. Network analysis was employed to depict the interrelation of symptom clusters and identify core and bridge symptoms. The symptoms were classified by severity into five clusters: oral, gastrointestinal, fatigue-related, body image, and pain-sleep. Within the symptom network, the core symptoms were pain, "I don't look like myself," and nausea, while the critical bridge symptoms included pain, itching, and feeling bloated. The strongest connections were observed between nausea and vomiting, followed by taste changes and dry mouth, as well as weight loss and "I don't look like myself." In patients receiving targeted immunotherapy for intermediate and advanced liver cancer, multiple symptoms can emerge simultaneously, forming interconnected clusters. By identifying and intervening in core and bridge symptoms, personalized management strategies can be developed to relieve other symptoms and disrupt connections between symptom clusters, thereby enhancing symptom management efficacy. This study has significant clinical and research implications, offering new insights to improve patients' quality of life and treatment outcomes.

Integrating bioinformatics and machine learning methods to analyze diagnostic biomarkers for HBV-induced hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a malignant tumor. It is estimated that approximately 50–80% of HCC cases worldwide are caused by hepatitis b virus (HBV) infection, and other pathogenic factors have been shown to promote the development of HCC when coexisting with HBV. Understanding the molecular mechanisms of HBV-induced hepatocellular carcinoma (HBV-HCC) is crucial for the prevention, diagnosis, and treatment of the disease. In this study, we analyzed the molecular mechanisms of HBV-induced HCC by combining bioinformatics and deep learning methods. Firstly, we collected a gene set related to HBV-HCC from the GEO database, performed differential analysis and WGCNA analysis to identify genes with abnormal expression in tumors and high relevance to tumors. We used three deep learning methods, Lasso, random forest, and SVM, to identify key genes RACGAP1, ECT2, and NDC80. By establishing a diagnostic model, we determined the accuracy of key genes in diagnosing HBV-HCC. In the training set, RACGAP1(AUC:0.976), ECT2(AUC:0.969), and NDC80 (AUC: 0.976) showed high accuracy. They also exhibited good accuracy in the validation set: RACGAP1(AUC:0.878), ECT2(AUC:0.731), and NDC80(AUC:0.915). The key genes were found to be highly expressed in liver cancer tissues compared to normal liver tissues, and survival analysis indicated that high expression of key genes was associated with poor prognosis in liver cancer patients. This suggests a close relationship between key genes RACGAP1, ECT2, and NDC80 and the occurrence and progression of HBV-HCC. Molecular docking results showed that the key genes could spontaneously bind to the anti-hepatocellular carcinoma drugs Lenvatinib, Regorafenib, and Sorafenib with strong binding activity. Therefore, ECT2, NDC80, and RACGAP1 may serve as potential biomarkers for the diagnosis of HBV-HCC and as targets for the development of targeted therapeutic drugs.

Development and validation of an MR-driven dose-of-the-day procedure for online adaptive radiotherapy in upper gastrointestinal cancer patients

Objective. To develop and validate a dose-of-the-day (DOTD) treatment plan verification procedure for liver and pancreas cancer patients treated with an magnetic resonance (MR)-Linac system. Approach. DOTD was implemented as an automated process that uses 3D datasets collected during treatment delivery. Particularly, the DOTD pipeline’s input included the adapt-to-shape (ATS) plan—i.e. 3D-MR dataset acquired at beginning of online session, anatomical contours, dose distribution—and 3D-MR dataset acquired during beam-on (BON). The DOTD automated analysis included (a) ATS-to-BON image intensity-based deformable image registration (DIR), (b) ATS-to-BON contours mapping via DIR, (c) BON-to-ATS contours copying through rigid registration, (d) determining ATS-to-BON dosimetric differences, and (e) PDF report generation. The DIR process was validated by two expert reviewers. ATS-plans were recomputed on BON datasets to assess dose differences. DOTD analysis was performed retrospectively for 75 treatment fractions (12-liver and 5-pancreas patients). Main results. The accuracy of DOTD process relied on DIR and mapped contours quality. Most DIR-generated contours (99.6%) were clinically acceptable. DICE correlated with depreciation of DIR-based region of interest mapping process. The ATS-BON plan difference was found negligible (<1%). The duodenum and large bowel exhibited highest variations, 24% and 39% from fractional values, for 5-fraction liver and pancreas. For liver 1-fraction, a 62% variation was observed for duodenum. Significance. The DOTD methodology provides an automated approach to quantify 3D dosimetric differences between online plans and their delivery. This analysis offers promise as a valuable tool for plan quality assessment and decision-making in the verification stage of the online workflow.

Clinical Therapy: HAIC Combined with Tyrosine Kinase Inhibitors and Programmed Cell Death Protein-1 Inhibitors versus HAIC Alone for Unresectable Hepatocellular Carcinoma.

The majority of new diagnoses of hepatocellular carcinoma (HCC) still pertain to unresectable cases. Currently, the combination therapy of tyrosine kinase inhibitors (TKIs) and programmed cell death protein-1 (PD-1) inhibitors has become the mainstream treatment. According to multiple clinical guidelines, it is strongly advised to consider local therapy as the primary treatment choice for uHCC. This research was conducted to examine the safety and effectiveness of combining hepatic arterial infusion chemotherapy (HAIC) with TKIs and PD-1 inhibitors for the treatment of uHCC. Between 2015 and 2020, 208 HCC patients received HAIC alone or HAIC in combination with TKIs and PD-1 inhibitors. The overall survival(OS), and progression-free survival(PFS) and the best treatment response were compared between the two treatment groups. Propensity score matching (PSM)was used to minimize confounding bias. Among the enrolled patients, 116 patients (55.8%) received combination therapy, while 92 patients (44.2%) received HAIC alone. The baseline characteristics were similar between the two groups. After PSM, 82 pairs of well-matched liver cancer patients were selected; the overall response rate in the combination group trended better than that in the HAIC alone group. The hazard ratios (HRs) for OS and PFS of the combination approach compared to the HAIC-alone approach were 0.47 (95% CI, 0.322-0.687; p<0.001) and 0.58 (95% CI, 0.397-0.848; p=0.005), respectively. For uHCC patients, combination therapy can provide better OS and PFS compared to HAIC alone.

Application of radioactive iodine-125 microparticles in hepatocellular carcinoma with portal vein embolus.

Radioactive iodine-125 (125I) microparticle therapy is a new type of internal radiation therapy that has shown unique advantages in the treatment of malignant tumors, especially hepatocellular carcinoma. Patients with hepatocellular carcinoma frequently experience portal vein embolism, which exacerbates the difficulty and complexity of treatment. 125I particles, used in local radiotherapy, can directly act on tumor tissue and reduce damage to surrounding healthy tissue. Through retrospective analysis, this study discussed the efficacy and safety of radioactive 125I particles in portal vein embolization patients with hepatocellular carcinoma in order to provide more powerful evidence supporting clinical treatment. To investigate the effect of transcatheter arterial chemoembolization combined with portal vein 125I particle implantation in the treatment of primary liver cancer patients with portal vein tumor thrombus and its influence on liver function. The clinical data of 96 patients with primary liver cancer combined with portal vein tumor thrombus admitted to our hospital between January 2020 and December 2023 were retrospectively analyzed. Fifty-two patients received treatment with transcatheter arterial chemoembolization and implantation of 125I particles in the portal vein (combination group), while 44 patients received treatment with transcatheter arterial chemoembolization alone (control group). The therapeutic effects on tumor lesions, primary liver cancer, and portal vein tumor embolisms were compared between the two groups. Changes in relevant laboratory indexes before and after treatment were evaluated. The t test was used to compare the measurement data between the two groups, and the χ 2 test was used to compare the counting data between groups. The tumor lesion response rate in the combination group (59.62% vs 38.64%) and the response rate of patients with primary liver cancer complicated with portal vein tumor thrombus (80.77% vs 59.09%) were significantly greater than those in the control group (χ 2 = 4.196, 5.421; P = 0.041, 0.020). At 8 wk after surgery, the serum alpha-fetoprotein, portal vein main diameter, and platelet of the combined group were significantly lower than those of the control group, and the serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin were significantly greater than those of the control group (t = 3.891, 3.291, 2.330, 3.729, 3.582, 4.126; P < 0.05). The serum aspartate aminotransferase, alanine aminotransferase, and total bilirubin levels of the two groups were significantly greater than those of the same group 8 wk after surgery (P < 0.05), and the peripheral blood platelet, alpha-fetoprotein, and main portal vein diameter were significantly less than those of the same group before surgery (P < 0.05). In patients with primary liver cancer and a thrombus in the portal vein, transcatheter arterial chemoembolization plus portal vein 125I implantation is more effective than transcatheter arterial chemoembolization alone. However, during treatment it is crucial to pay attention to liver function injury caused by transcatheter arterial chemoembolization.