Survival Of Hepatocellular Carcinoma Patients Research Articles

Abstract 3981: The GZMK CD8 T cells cluster defined by single-cell transcriptome profiling with innate-like functions is a predictor of survival in hepatocellular carcinoma patients

Abstract Hepatocellular carcinoma (HCC), the sixth most common cancer globally in 2020, is closely associated with hepatitis B or C infections and non-alcoholic steatohepatitis (NASH). Despite advancements in surgical and systemic therapies for early and advanced stages, tumor relapse and poor prognosis remain significant challenges, necessitating improved therapeutic approaches. This study highlights the role of GZMK-expressing CD8+ T cells in HCC, identified through single-cell transcriptome profiling. These cells exhibit transcriptional profiles similar to hepatotoxic CD8+ T cells in chronic hepatitis B and innate-like CD8+ T cells in chronic hepatitis C. GZMK CD8+ T cells are enriched with tissue-resident memory traits and are detectable in peripheral blood and tumor tissues. Furthermore, within the tumor microenvironment, GZMK CD8 cells expressed surface receptors resembling those of NK cells, allowing them to release IFN-γ and exert non-antigen specific innate-like cytotoxic effects. These GZMK CD8+ T cells could be identified as CD38+HLA-DR+ CD8+ T cells by flow cytometry. These CD38+HLA-DR+ CD8+ T cells increased in the peripheral blood of HCC patients and accumulated in tumor tissue. Cytokines such as IL-12, IL-15, and IL-18 were shown to stimulate the proliferation of CD38+HLA-DR+ CD8+ T cells, enhancing their production of IFN-γ and granzyme B, as well as their expression of NK-like receptors and effector molecules. These bystander-activated CD38+HLA-DR+ CD8+ T cells, derived from effector memory (EM) and effector memory RA (EMRA) subsets, displayed cytotoxicity against K562 and THP-1 cell lines through DNAM-1, granzyme B, and perforin. A high GZMK CD8+ T cell signature was strongly associated with improved overall survival (OS) and progression-free survival (PFS) in the TCGA-HCC database. These findings suggest that GZMK CD8+ T cells have a significant impact on survival in HCC, possibly through their innate-like cytotoxic functions. This unique subset may serve as a biomarker and a potential therapeutic target in HCC management. Citation Format: Wei-Ting Ku, Chien-Hao Huang, Jian-He Fan, Cheng-Heng Wu, Tsung-Han Wu, Wei Teng, Po-Ting Lin, Chung-Wei Su, Yung-Chang Lin, Chun-Yen Lin. The GZMK CD8 T cells cluster defined by single-cell transcriptome profiling with innate-like functions is a predictor of survival in hepatocellular carcinoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3981.

Abstract 4318: Genome-wide in vivo CRISPR screen identifies the role of SRSF9 in immunotherapy response regulation in hepatocellular carcinoma

Abstract Hepatocellular carcinoma (HCC) is a leading malignant tumor globally and the second-highest cause of cancer-related mortality. The insidious nature and high recurrence rates of HCC largely necessitate systemic therapies for many patients, particularly those based on immune checkpoint inhibitors. For advanced HCC, the combination of atezolizumab and bevacizumab (Atezo+Beva) has become the preferred first-line treatment, providing superior survival benefits compared to sorafenib. However, the response rate to this therapy remains under 30%, with the underlying resistant mechanism still unclear. Therefore, identifying and characterizing predictive biomarkers associated with the response to Atezo+Beva therapy is essential for improving clinical prognosis in patients with advanced HCC. Here, we performed an in vivo genome-wide CRISPR screen model after anti-programmed death ligand 1 (anti-PD-L1) and anti-vascular endothelial growth factor a (anti-VEGFa) treatment to investigate genomic modulators of the immunotherapy response in HCC. Our screening identified serine and arginine rich splicing factor 9 (SRSF9) as a critical gene involved in the anti-immunotherapy regulation. Knockout of SRSF9 in mouse tumor cells significantly enhanced the sensitivity of primary tumors and the lung metastasis to anti-PD-L1 and anti-VEGFa treatment. This finding was further validated using SRSF9-overexpression mouse model. Functional assays indicated that without immunotherapy SRSF9 had a minimal direct effect on the proliferation of multiple HCC cell lines, aligning with the analytical results derived from the DepMap database. Clinically, SRSF9 expression was increased in multiple cancer types compared to normal counterparts and was positively correlated with poor survival in HCC patients following Atezo-Bev therapy. Furthermore, high SRSF9 expression could negate the prognostic advantage typically seen in patients with strong CD8+ T cell function. In addition, SRSF9 could decrease the secretion of interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) in tumor environment. These suggested a potential role for SRSF9 in downregulating CD8+ T cell activity. The underlying mechanism of how SRSF9 inhibits the response of HCC patients to Atezo+Beva therapy still needs further investigation. In conclusion, our study reveals the significant role of SRSF9 in modulating the response to immunotherapy in HCC, indicating its substantial potential for expanding the cohort of patients who may benefit from Atezo+Beva therapy and enhancing their prognosis. Further exploration of the underlying mechanisms will be undertaken in the future. Citation Format: Nanzhou Yu, Jie Luo, Beibei Ru, Renyue Ji, Lanqi Gong, Peng Jiang, Xinyuan Guan. Genome-wide in vivo CRISPR screen identifies the role of SRSF9 in immunotherapy response regulation in hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4318.

Abstract 6935: Combinatorial treatment with small molecule inhibitors C26-A6 and MYCi975 in hepatocellular carcinoma (HCC)

Abstract Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer. The median overall survival of advanced HCC patients is only 6.5-10.7 months. Identifying novel therapeutic targets and developing effective combinatorial treatment is highly relevant to HCC. Two oncogenes, Astrocyte elevated gene-1(AEG-1) and MYC (coding for c-Myc) are co-amplified in HCC patients and cooperate to promote aggressive, metastatic HCC. MYC is a driver oncogene for HCC and overexpression of MYC alone can initiate HCC. AEG-1 overexpression itself cannot induce HCC but it can significantly accelerate tumor progression once initiated. The objective is to evaluate the therapeutic efficacy of the combination of C26-A6 and MYCi975, small molecule inhibitors of AEG-1 and MYC, respectively, for HCC. Human HCC cell lines SNU-449, SNU-182, HuH-7, and Hep3B were treated with C26-A6 and MYCi975, alone or in combination. Optimum concentration of the inhibitors, to be used in combination, was determined by titration experiments. Cell viability was measured by MTT [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide] and colony formation assays. Data was analyzed by a two-tailed T-test. Cell invasion was analyzed by Matrigel invasion assay. Differential gene expression was analyzed by RNA-sequencing (RNA-seq) and Ingenuity Pathway Analysis (IPA). In all four cell lines, MYCi975 was more potent than C26-A6 to inhibit cell viability. For MYCi975, MTT assay over 5 days identified the IC50 ranging between 2-4 μM, while for C26-A6 IC50 was more than 100 μM. A combination of C26-A6 and MYCi975 showed significant and synergistic inhibition in viability. Similarly, the combination treatment showed significant inhibition in cell invasion compared to single agent treatment. SNU-449 cells were treated with C26-A6, MYCi975, or C26-A6+MYCi975 combination for 24 h and RNA-seq was performed. This time point was chosen to identify differentially expressed genes (DEGs) by inhibitor treatment before cell death starts. IPA of DEGs revealed that MYCi975 inhibited pathways associated with cell proliferation, C26-A6 inhibited pathways regulating cell migration, invasion, and metastasis, and the combination inhibited both. Inhibition of several oncogenes, such as STAT3, E2F2, and FOXM1 which are associated with poor prognosis and aggressive HCC, was identified by the combination treatment. MYCi975 inhibited cell proliferation, while C26-A6 inhibited cell invasion indicating that in an in vivo setting C26-A6 and MYCi975 combination might inhibit both primary and metastatic tumors and the combination might exert a synergistic inhibitory effect compared to either agent alone. Studies are ongoing to evaluate in vivo therapeutic efficacy of the treatment and elucidate the underlying mechanism mediating the effects of the combination treatment. Citation Format: Eva Davis, Ali G. Ermi, Devanand Sarkar. Combinatorial treatment with small molecule inhibitors C26-A6 and MYCi975 in hepatocellular carcinoma (HCC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6935.

Safety and Therapeutic Outcomes of Adjuvant Immunotherapy With Autologous Cytokine-induced Killer Cells for Patients With Hepatocellular Carcinoma Beyond Milan Criteria After Liver Transplantation.

Adjuvant immunotherapy with autologous cytokine-induced killer (CIK) cells for hepatocellular carcinoma (HCC) remains understudied in liver transplant patients because of potential risks of acute rejection and diminished efficacy by immunosuppression. This study examined the safety and effectiveness of CIK therapy in patients with HCC exceeding the Milan criteria, treated at 2 Korean hospitals between 2019 and 2021. We analyzed clinical outcomes of 16 patients who underwent CIK therapy compared with 44 propensity-matched controls who did not receive CIK therapy. CIK cells were administered in 6 escalating doses, either 3 or 6 times over the course of weeks 4, 5, 6, 8, 10, and 12 posttransplantation. CIK therapy was well-tolerated without significant treatment-related adverse reactions. Maximal tolerated dose of CIK cells was 10 × 109, which had been repeated 6 times. The CIK group exhibited higher 2-y HCC recurrence-free (87.5% versus 62.9%, P = 0.027) and patient survival (100% versus 81.5%, P = 0.002) rates, with no significant difference in rejection-free survival rates (92.9% versus 95.0%, P = 0.926) compared with the no-CIK group. Subgroup analysis showed that the CIK group in patients with high retreat scores, elevated R3-α-fetoprotein scores, and those beyond the University of California San Francisco criteria had improved HCC recurrence-free survival. Immunological evaluation showed elevated CD8+ T cells and polymorphonuclear myeloid-derived suppressor cells with transient increases in granzyme B and tumor necrosis factor-α levels in the CIK group. These findings advocate CIK therapy as a safe and effective, potential adjuvant treatment for HCC beyond Milan criteria after transplantation, supporting further validation trials.

Impact of frailty on the long-term prognosis of the elderly with hepatocellular carcinoma treated with transarterial chemoembolization

Transcatheter arterial chemoembolization (TACE) is a standard treatment for unresectable, intermediate, or advanced-stage hepatocellular carcinoma (HCC), especially in elderly patients. The modified 5-item frailty index (mFI-5) is a concise, comorbidity-based risk stratification tool proven to effectively predict adverse outcomes. However, the prognostic capacity of the mFI-5 in elderly HCC patients after TACE is unclear. As such, we retrospectively analyzed clinical data from elderly HCC patients (age ≥ 65 years) who received their first TACE between November 2018 and November 2020 at the Department of Interventional Radiology, Affiliated Hospital of Xuzhou Medical University. The mFI-5 was calculated based on the presence of five co-morbidities: congestive heart failure within 30 days prior to surgery; insulin-dependent or noninsulin-dependent diabetes mellitus; chronic obstructive pulmonary disease (COPD) or pneumonia; partially dependent or totally dependent functional health status at time of surgery; and hypertension requiring medication. Patients were divided into two groups based on mFI-5 scores: mFI-5 ≥ 2 (‘frail’) and mFI-5 < 2 (‘non-frail’). The primary outcomes were overall survival (OS) and progression-free survival (PFS).Among the 143 patients, 97 were in the mFI-5 < 2 group and 46 in the mFI-5 ≥ 2 group. The median OS was 40.0 months (95% confidence interval [CI]: 35.0–47.0) in the non-frail group vs. 24.0 months (95% CI: 22-NA) in the frail group (hazard ratio [HR] = 3.343, 95% CI: 1.802–6.201, p < .001). The median PFS was 7.0 months (95% CI: 4.0–11.0) vs. 3.0 months (95% CI: 2.0–9.0) (HR = 1.507, 95% CI: 0.996–2.280, p = .053). Cox regression identified mFI-5, alpha-fetoprotein (AFP) as independent predictors of OS. The mFI-5 is a useful predictor of long-term survival in elderly HCC patients treated with TACE, suggesting that incorporating frailty assessments can optimize treatment strategies and improve outcomes.

Transplant Versus Non-Transplant Hepatocellular Carcinoma Patient Characteristics And Survival

Background and Objectives: Survival of patients treated by liver transplantation for hepatocellular carcinoma (HCC) remains excellent, with more that 75% 5-year survival. By contrast, overall survival of HCC patients in large populations remains less than 30% at 5 years. Our aims were to examine whether this discrepancy was due to the low proportion of patients who get treated by liver transplant in our HCC cohort and why. Materials and Methods: New patients presenting with HCC at our institution over the last 5 years were evaluated in this prospective study. Baseline tumor evaluation was done by CAT scan and routine hematology and liver function laboratory values were recorded, as was survival. Results: Almost all new HCC patients (n=628) over 5 years at Inonu University hospital were evaluated. 191 patients (30.4% of the total cohort) received potentially curative and survival-extending liver transplants, while 384 patients (61.1% of the total cohort) received non-surgical therapies, 53 patients (8.4%) could not receive any oncologic therapy. Transplanted HCC patients had smaller, less aggressive HCCs, worse liver function and a mean survival of 43.06 + 1.41 months. Non-surgically treated HCC patients had larger, more aggressive HCCs, better liver function, and a mean survival of 31.51±1.53 months, p&lt;0.001. No-therapy patients had both most aggressive HCCs and worst liver function, and a mean survival of 4.41±0.95 months. Conclusions: Survival after liver transplant was significantly longer than without liver transplant. Future efforts need to focus on HCC prevention, early detection, and in identifying/treating additional HCC patients who could be rendered transplant-eligible. Lay summary. Long survival is mainly associated with liver transplant, yet only one third of our patients were eligible for transplant, because the other patients had tumors that were too advanced for transplantation at presentation. Simple Summary: Hepatocellular carcinoma (HCC) is essentially cured (&gt;75% 5-years survival) when patients within accepted criteria are treated by liver transplant. Other, non-surgical treatments result in dramatically shorter survival times. We collected data on all patients being referred for HCC treatment over a 5-year period and found that only 30.4% were offered transplant. To investigate the reasons, we compared baseline clinical and tumor characteristics of all new patients on presentation at our institute and found that transplanted patients have smaller and less aggressive HCCs. We discuss whether this is due to a different HCC biology or absence of surveillance or whether the transplant criteria might be too stringent. Keywords : HCC, transplant, size, survival, cirrhosis.

Circulating miR-485-5p as a potential diagnostic and prognostic biomarker for HCV-related hepatocellular carcinoma

Hepatitis C virus (HCV) is the predominant viral cause of hepatocellular carcinoma (HCC). Early detection and use of reliable biological markers can improve survival for HCC patients. MiR-485-5p was identified as a tumor-suppressing microribonucleic acid (miRNA) in some human cancers and was recently found to be downregulated in HCC tissues, signifying its utility as a promising biomarker. We aimed to investigate the potential role of circulating miR-485-5p as a novel diagnostic and prognostic biomarker for HCV-related HCC. This case–control study included 50 patients with HCC associated with HCV, 50 patients with HCV-related liver cirrhosis, and 50 healthy controls. History gathering, physical examination, laboratory, and imaging assessments were performed. A quantitative real-time polymerase chain reaction was used to measure miR-485-5p levels. Serum miR-485-5p values demonstrated a stepwise decline pattern from the control group to cirrhotic patients, with the HCC group exhibiting the lowest levels (p < 0.001). HCC patients with early BCLC stages had significantly lower miR-485-5p levels than those with late stages (p = 0.004). The miR-485-5p displayed a better performance in predicting HCV-related HCC with a greater area under the ROC curve (AUC) than alpha-fetoprotein (AFP) (AUC and sensitivity 0.921 and 92.0 versus 0.704 and 64.0, respectively) (p < 0.001). Also, its performance in predicting HCC prognosis surpassed that of AFP (AUC and sensitivity 0.872 and 85.19 versus 0.695 and 62.96, respectively) (p < 0.001). Circulating miR-485-5p is a promising, accurate, and noninvasive biomarker for the early detection and prediction of prognosis in patients with HCV-linked HCC.

Risk Factors and Survival Analysis of Spontaneously Ruptured Hepatocellular Carcinoma: A Retrospective Cohort Study in Bilateral Centers.

This study aimed to analyze risk factors for spontaneously ruptured hepatocellular carcinoma (HCC) and investigate the impact of spontaneous tumor rupture (STR) on the long-term survival of HCC patients treated by transcatheter arterial chemoembolization (TACE). A retrospective cohort of patients with a diagnosis of HCC was divided into the ruptured group and the non-ruptured group. Uni- and multivariate logistic regression analyses were performed for risk factors. The survival outcomes for the patients treated with hepatectomy, TACE, or best supportive care (BSC) in ruptured group were compared. The prognosis of HCC patients treated with TACE were compared using propensity score-matching (PSM). The study enrolled 1103 HCC patients for risk factors analysis. Logistic regression analysis showed that male sex, liver cirrhosis, tumor protrusion, tumor diameter greater than 5cm, macrovascular invasion, alpha fetoprotein (AFP) of 400ng/mL or higher, and ascites were independent risk factors for STR. A COX regression analysis indicated that tumor diameter greater than 5cm, AFP of 400ng/mL or higher, and STR were independent prognostic factors for overall survival (OS). Furthermore, tumor diameter greater than 5 cm and macrovascular invasion were independent prognostic factors for progress-free survival (PFS). In ruptured group, treatment with hepatectomy indicated the best prognosis, followed by treatment with TACE and BSC. Also, in TACE group, the non-ruptured HCC patients had significant longer OS than the ruptured HCC patients, whereas PFS showed no statistical difference before or after PSM. Male sex, liver cirrhosis, tumor protrusion, tumor diameter greater than 5cm, macrovascular invasion, AFP of 400ng/mL or higher, and ascites are independent risk factors for STR. In ruptured group, treatment with hepatectomy indicated the best prognosis, followed by treatment with TACE and BSC. For the HCC patients treated with TACE, STR was independent prognostic factor for OS but not PFS.

Immune regulation and clinical response of Chinese herbal injections combined with TACE in hepatocellular carcinoma: a cumulative logit regression and Bayesian network meta-analysis.

This study evaluated the immunomodulatory effects and clinical efficacy of Chinese herbal injections (CHIs) combined with transcatheter arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) patients using cumulative logit regression and Bayesian network meta-analysis. A systematic review of 48 randomized controlled trials (RCTs) involving 4,293 HCC patients was conducted using PubMed, Cochrane Library, EMBASE, Scopus, and Google Scholar. Outcomes included immune markers (CD3+, CD4+, CD8+, CD4+/CD8+ ratio, and NK cells), clinical response rate, and overall survival (6-month, 1-year, and 2-year). Cumulative logit regression and Bayesian network meta-analysis were applied to synthesize ordinal and continuous outcomes. Compared to TACE alone, Aidi, Compound Kushen, and Huachansu significantly enhanced the immune function. Aidi increased CD3+ T cells (MD = 10.95, 95% CI: 8.04-13.86), CD4+ T cells (MD = 7.13, 4.37-9.89), CD4+/CD8+ ratio (MD = 0.31, 0.20-0.41), and NK cells (MD = 6.30, 4.49-8.12), while Compound Kushen showed the highest CD4+/CD8+ improvement (MD = 0.47, 0.37-0.56) and NK cell elevation (MD = 9.11, 7.32-10.91). Huachansu increased CD3+ T cells (MD = 8.74, 4.43-13.06) and CD4+ T cells (MD = 8.00, 4.21-11.80). For clinical outcomes, Compound Kushen (HR = 2.57, 1.9-3.59) and Aidi (HR = 2.28, 1.68-3.18) improved clinical response rates versus TACE. Aidi enhanced 6-month (OR = 2.57, 1.44-4.56) and 1-year survival (OR = 2.46, 1.56-3.88), whereas Huachansu (OR = 3.47, 2.42-4.97) and Compound Kushen (OR = 2.91, 1.07-7.89) improved 2-year survival. Aidi, Compound Kushen, and Huachansu enhance immune function and survival in HCC patients when combined with TACE. Compound Kushen showed the most significant immunomodulatory effects, while Aidi and Huachansu improved short- and long-term survival, respectively. Further high-quality head-to-head RCTs are required to validate these results.

Association between allopurinol and hepatocellular carcinoma: analysis of genetic risk and patient survival

BackgroundDespite the widespread clinical use of allopurinol for managing hepatocellular carcinoma (HCC) and gout, its potential hepatotoxicity and its effect on the risk of HCC remain unclear. This study aimed to comprehensively assess the potential correlations between allopurinol exposure and HCC risk.MethodsWe utilized genome-wide association study data from the IEU OpenGWAS project as instrumental variables (IVs) for Mendelian randomization (MR) analysis to investigate the causal relationship between allopurinol and HCC. Subsequently, we investigated the potential mediating factors (gout, liver fat, and percentage of liver fat, etc.) between allopurinol use and HCC. Furthermore, we analyzed assessed survival outcomes using the Kaplan–Meier method to compare patient subgroups by differential Xanthine dehydrogenase (XDH) expression.ResultsMR analysis established a causal link between allopurinol use and increased HCC risk (OR: 1.013, 95% CI 1.004–1.023, p = 0.006). Causal relationships were also observed between gout (OR: 1.011, p = 0.008) and HCC. Mediation analysis indicated that gout mediated 61.6% of the effect of allopurinol on HCC. Survival analysis showed that higher expression of XDH was associated with improved survival of HCC patients (HR = 0.62, 95% CI 0.441–0.884, p = 0.008), indicating a 38% decrease in mortality risk compared to the lower expression group.ConclusionsThis study demonstrated a causal relationship between allopurinol use and an increased risk of HCC based on genetic evidence. Allopurinol should be used with caution in patients with or at risk for HCC.

TMEM115 as an Oncogenic and Immunological Biomarker in Hepatocellular Carcinoma.

Transmembrane (TMEM) proteins are involved in fundamental biological processes such as material transport and signal transduction. TMEM115 is a member of the TMEM protein family, but its significance in hepatocellular carcinoma (HCC) remains unclear. In this study, we investigate the clinical predictive significance and potential functions of TMEM115 in HCC. Bioinformatics was used to investigate TMEM115 mRNA expression and immune infiltration score. Through multiplex immunohistochemistry analysis, we assessed its protein expression and association with HCC patient clinical features, prognosis and immune cell infiltration in HCC. Through invitro and invivo experiments, we evaluated the biological functions of TMEM115 in HCC cells and its impact on the immune microenvironment. TMEM115 mRNA and protein levels were significantly higher in HCC tissues compared to paracancerous liver tissues. Its protein expression correlated with clinical characteristics and overall survival in HCC patients. In HCC tissues, higher TMEM115 protein expression corresponded to lower proportions of CD66b+ neutrophils and CD8+ T cells and a higher proportion of CD4+ T cells. Furthermore, patients with low TMEM115 expression displayed higher programmed cell death ligand-1 and lower lymphocyte activation gene 3 protein expression. Functionally, TMEM115 knockdown inhibited the proliferation, migration and invasion of HCC cells. In orthotopic models, TMEM115 knockdown inhibited the growth of HCC and affected the infiltration of immune cells. Our findings show TMEM115 as a promising prognostic indicator for HCC and hold promise in predicting responses to immune therapy, emphasising its potential clinical relevance and intricate involvement in the immune microenvironment of HCC.

A Potassium Channel-Related Signature for Prognosis and Immune Landscape Prediction of Hepatocellular Carcinoma.

Potassium channel-related genes (PCRGs) play an important role in hepatocellular carcinoma (HCC) development, recurrence, and immunotherapy tolerance. We aimed to develop a new prognostic model associated with PCRGs that can be used for prognosis and immunotherapy prediction in HCC patients. The transcriptional profiles and clinical data related to HCC were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Differentially expressed PCRGs were identified using the "edgeR" package. Prognostic model associated with PCRGs were constructed using univariate analysis, least absolute shrinkage and selection operator (LASSO), and multivariate regression analysis. The prognostic value of the model was evaluated through Kaplan-Meier (K-M) survival analysis and receiver operating characteristic (ROC) curves. Additionally, the tumor immune microenvironment was assessed using single sample gene set enrichment analysis (ssGSEA) and the CIBERSORT algorithm. Finally, potential drugs targeting signature genes were predicted. We successfully constructed a prognostic signature based on PCRGs, and the prognostic results were superior in the low-risk group. The nomogram demonstrated satisfactory predictive performance in estimating overall survival (OS) in HCC patients. The results of immune cell infiltration and predictions of immunotherapy response revealed that the low-risk group exhibited a more favorable response to immunotherapy. In addition, signature gene expression was significantly correlated with antitumor drug sensitivity. In conclusion, the characteristics of PCRGs serve as valuable tools for accurately assessing the prognosis and tumor microenvironment of HCC patients. Additionally, PCRGs markers can facilitate precision therapy in HCC management.

Current Advancements in Serum Protein Biomarkers for Hepatitis B Virus-Associated Hepatocyte Remodeling and Hepatocellular Carcinoma.

Hepatitis B virus (HBV)-related liver cancer is the third most common cause of cancer-related death globally. Hepatocyte remodeling, also known as hepatocyte transformation and immortalization, and hepatocellular carcinoma (HCC), are brought on by persistent inflammation caused by HBV in the host hepatocytes. One of the main concerns in the perspective of HBV-induced hepatocyte remodeling and liver cancer is accurately identifying cancer stages to maximize early screening and detection. Biological signatures have a significant impact on solving this problem. This review article aimed to discuss the novel serum protein biomarkers for HBV-induced hepatocyte remodeling and HCC. The information was collected from various peer-reviewed journals through electronic searches utilizing various search engines, including PubMed, Google Scholar, HINARI, and Cochrane Library from 2017 to 2024. Keywords for searches included "serum protein biomarkers in HBV-HCC," "blood-based biomarkers in HBV-HCC," and "viral biomarkers for HBV-HCC." Recently, novel protein signatures have been discovered for the early diagnosis, treatment, and prognosis of HBV-induced hepatic cell remodeling and HCC from proteomic data sets. We have discussed the recent literature on the clinical utility of the protein signatures for the diagnosis and forecasting of HBV-associated hepatocyte remodeling and HCC, including golgi protein 73 (GP73), glypican-3 (GPC3), midkine (MDK), des-γ-carboxy-prothrombin (DCP), von Willebrand factor (vWF), pentraxin 3 (PTX3), pseudouridine synthases 7 (PUSs 7), squamous cell carcinoma antigen (SCCA), and osteopontin (OPN). All these protein markers also exhibit the survival of HBV-related HCC patients, the proliferation, migration, antiapoptosis, mitogenesis, transformation, and angiogenesis of HBV-infected hepatocytes.

Association of Hepatoma Arterial-embolization Prognostic Score with Survival in Hepatocellular Carcinoma Patients undergoing Transcatheter Arterial Chemoembolization

Introduction: Hepatocellular carcinoma (HCC) ranked as the third leading cause of cancer-related deaths worldwide. Hepatoma Arterial-embolization Prognostic (HAP) score was suggested as a survival predictor for HCC patients undergoing Transcatheter Arterial Chemoembolization (TACE). Objectives: This study aimed to analyse the association of HAP score with survival in HCC patients undergoing TACE. Methods: This was survival analysis with longitudinal study. The Kaplan-Meier curve was used for survival analysis, while Cox Regression test was used to analyse univariate and multivariate association between HAP score and its components to survival. Results: There were 100 patients HCC who underwent TACE at a tertiary hospital between January 2019 and September 2022. The overall survival (OS) median was 7 months, while the 12-months survival rate was 9%. The 12-months survival rates of HAP A, HAP B, HAP C and HAP D were 25%, 23.3%, 0 and 0, respectively. There was association between HAP score and 12 months’ survival of HCC patients undergoing TACE (hazard ratio (HR) 3.187, 95% confidence interval (CI) 2.002–5.074, p&lt;0.001). Conclusions: HAP score has a prognostic value in predicting survival outcomes for HCC patients undergoing TACE.

Abstract A036: Comparison of immunotherapies response in hepatocellular carcinoma HCC with viral hepatitis vs non-viral hepatitis

Abstract Background: Hepatocellular carcinoma (HCC), the most common liver cancer, accounts for 80% of diagnosed cases. Immunotherapy is increasingly used for advanced HCC and other solid tumors. Approximately 13% of cancers are associated with infections. HCC etiology varies by regionally, with 54% of cases in Asia and sub-Saharan Africa due to hepatitis B, while hepatitis C is more common in Italy and Japan. Hepatitis infections disrupt liver signaling, causing inflammation and abnormal cell regeneration. In HCC progression, inflammation serves as a “double-edged sword.” While chronic inflammation is a significant driver of tumor development and immune evasion, it can also promote tumor cell death, either directly through ferroptosis or indirectly by enhancing anticancer immune responses, thereby potentially inhibiting HCC progression. This study aimed to evaluate immunotherapy response in HCC associated with viral hepatitis compared to non-viral hepatitis. Methods: HCC patients were analyzed using data from the cBioPortal database, from a cohort study of hepatobiliary cancers. Only HCC patients who received nivolumab, pembrolizumab, atezolizumab, bevacizumab, durvalumab, tremelimumab, ipilimumab, ramucirumab, or daratumumab, either as monotherapy or in combination were included. We excluded all cases of cholangiocarcinoma (CCA), HCC with CCA, and those not treated with immunotherapy. We calculated median overall survival (OS) for immunotherapy-treated HCC patients with viral hepatitis compared to those with non-viral hepatitis. Survival analysis was conducted using the Kaplan–Meier (KM) method. Results: Among 1,370 hepatobiliary cancer cases, 289 were identified as HCC. After excluding patients who did not receive immunotherapy, a total of 101 cases remained, of which 56 (55.4%) had viral HCC, and 45 (44.6%) had non-viral HCC. Most patients were white 62 (61%), and 27 (26%) had cirrhosis. Additionally, 66 (65%) had TERT mutations, 45 (43%) had TP53 mutations. Of the total, 52 (51%) had died, while 49 (48%) were still alive. All patients received at least one immunotherapy cycle, with 65 (64.4%) receiving it as a palliative setting. Viral HCC was associated with a median OS of 60 months (95% CI,38.24-NA), while non-viral HCC showed median OS of 40 months (95% CI,25.34-NA) (p=0.106). Conclusion: Our study highlighted that HCC patients with underlying viral infections achieve better outcomes from immunotherapy, evidenced by a longer OS compared to patients with non-viral HCC. This suggests that viral HCC may have a unique tumor biology or immune environment that enhances the response to immunotherapy, leading to improved survival outcomes relative to non-viral cases. Citation Format: Saifudeen Abdelrahim, Ebtesam Al-Najjar, Bayan Khasawneh, Abdullah Esmail, Ala Abudayyeh. Comparison of immunotherapies response in hepatocellular carcinoma HCC with viral hepatitis vs non-viral hepatitis [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Functional and Genomic Precision Medicine in Cancer: Different Perspectives, Common Goals; 2025 Mar 11-13; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(5 Suppl):Abstract nr A036.

Tumor Prognostic Risk Model Related to Monocytes/Macrophages in Hepatocellular Carcinoma Based on Machine Learning and Multi-Omics

Tumor-associated macrophages (TAMs) are crucial in hepatocellular carcinoma (HCC) development and invasion. This study explores monocyte/ macrophage-associated gene expression profiles in HCC, constructs a prognostic model based on these genes, and examines its relationship with drug resistance and immune therapy responses. Single-cell RNA sequencing(scRNA-seq) data from 10 HCC tissue biopsy samples, totaling 24,597 cells, were obtained from the GEO database to identify monocyte/macrophage-associated genes. A prognostic model was constructed and validated using external datasets and Western blot. Relationships between the model, clinical correlates, drug sensitivity, and immune therapy responses were investigated. From scRNA-seq data, 2,799 monocyte/macrophage marker genes were identified. Using the TCGA dataset, a prognostic model based on the single-gene UQCRH was constructed, stratifying patients into high-risk and low-risk groups based on overall survival rates. High-risk group patients showed reduced survival rates and higher UQCRH expression in tumor tissues. Western blot analysis further confirmed the elevated expression of UQCRH in HCC cell lines. Spatial transcriptomics analysis revealed that high UQCRH expression co-localized with malignant cells in the tumor tissue. Drug sensitivity analysis revealed that the high-risk group had lower sensitivity to sorafenib and axitinib. Immune therapy response analysis indicated poorer outcomes in the high-risk group, with more pronounced APC inhibition and a weaker IFN-II response. Clinical indicator analysis showed a positive correlation between high UQCRH expression and tumor invasion. Enrichment analysis of UQCRH and associated molecules indicated involvement in oxidative phosphorylation and mitochondrial electron transport. This study introduces a prognostic model for HCC patients based on monocyte/macrophage marker genes. The single-gene model predicts HCC patient survival and treatment outcomes, identifying high-risk individuals with varying drug sensitivities and immune suppression states.

Model Predicting Survival in Intermediate-Stage HCC Patients Reclassified for TACE Based on the 2022 BCLC Criteria

Background/Objectives: The Barcelona Clinic Liver Cancer (BCLC) staging system for hepatocellular carcinoma (HCC) was updated in 2022 to refine patient stratification, particularly in patients with intermediate-stage (BCLC B) HCC. Although transarterial chemoembolization (TACE) remains a key treatment for these patients, there is no prognostic model for survival outcomes based on the pretreatment factors of patients who meet the updated 2022 BCLC indications for TACE. The aim of this study was to develop a pretreatment risk model predicting overall survival (OS) in patients with intermediate-stage HCC and reclassified as candidates for TACE according to the updated 2022 BCLC criteria. Methods: This retrospective study included 658 HCC patients treated with first-line TACE according to the updated BCLC 2022 guidelines. Pretreatment factors such as the Child–Pugh score, tumor burden (up-to-11 criteria), bilobar tumor involvement, and serum alpha-fetoprotein (AFP) levels were analyzed. Cox proportional hazards models were used to identify significant predictors of OS, with these factors subsequently incorporated into a risk prediction model. Results: Significant predictors of OS included Child–Pugh score ≥ 7, bilobar tumor involvement, beyond up-to-11 criteria, and AFP ≥ 400 ng/mL. A risk model was developed using these factors, stratifying patients into low-, intermediate-, and high-risk groups. The median OS in the low-, intermediate-, and high-risk groups was 53, 35, and 21 months, respectively. Conclusions: The proposed pretreatment risk prediction model may be useful for predicting OS and guiding TACE candidacy in intermediate-stage HCC patients based on the updated 2022 BCLC guidelines.

TRIM29 reverses lenvatinib resistance in liver cancer cells by ubiquitinating and degrading YBX1 to inhibit the PI3K/AKT pathway.

TRIM29 reverses lenvatinib resistance in liver cancer cells by ubiquitinating and degrading YBX1 to inhibit the PI3K/AKT pathway.

Early CTLA4 increase in CD45+ blood cells: an emerging biomarker of atezolizumab-bevacizumab resistance and worse survival in advanced hepatocarcinoma.

Early CTLA4 increase in CD45+ blood cells: an emerging biomarker of atezolizumab-bevacizumab resistance and worse survival in advanced hepatocarcinoma.

Bioinformatics Identification of Shared Signaling Pathways and Core Targets Linking Benzo[a]pyrene Exposure to HCC Progression.

Bioinformatics Identification of Shared Signaling Pathways and Core Targets Linking Benzo[a]pyrene Exposure to HCC Progression.