Aim: Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, with heterogeneous responses to immune checkpoint inhibitors (ICIs). Activated CD8+ T cell plays pivotal role in antitumor immunity, yet their systematic integration into a prognostic and predictive molecular framework is lacking. Methods: RNA-seq data from 363 HCC patients in The Cancer Genome Atlas (TCGA) and validation cohorts (GSE76427, GSE14520) were analyzed by single-sample gene set enrichment analysis (ssGSEA). We quantified 28 tumor-infiltrating immune cell subsets and performed consensus clustering based on activated CD8+ T cell infiltration. Weighted gene co-expression network analysis (WGCNA) identified a CD8+ T cell associated gene module. Cox regression analysis selected 17 hub genes, from which an immune infiltration-based prognostic model was constructed and externally validated. The two risk groups were compared for prognosis, molecular features, and immunotherapy sensitivity using immune, stromal, stemness, and tumor immune dysfunction and exclusion (TIDE) scores. Results: We determined the proportion of activated CD8+ T lymphocytes associated with the coexpression network. Cluster 1 and low-risk groups exhibited higher immune infiltration and better prognosis (P < 0.05) than Cluster 2 and high-risk groups. Indicators of immunotherapy response - including lower mutation frequency, copy-number variations (CNVs), and stemness score, along with higher immune, stromal, and TIDE scores - suggested reduced ICI therapy efficacy in Cluster 1/low-risk groups, whereas the opposite pattern was observed in Cluster 2/high-risk groups. Conclusion: We established a robust prognostic classifier based on activated CD8+ T cell-related genes. This model may aid in identifying HCC patients with poor prognosis who are likely to benefit from immune checkpoint inhibitor therapy.

Tyrosine kinase inhibitor (TKI) resistance limits therapy for hepatocellular carcinoma (HCC). Integrating RNA-seq and public cohort data, we found consistent downregulation of the bile salt export pump (BSEP/ABCB11) in TKI-resistant HCC associated with poorer prognosis and reduced clinical response. Functional in vitro and xenograft studies, using BSEP overexpression/knockdown and TKI-resistant cell lines plus targeted metabolomics, showed BSEP expression deficiency leads to intracellular accumulation of primary conjugated bile acids (BAs)-especially glycocholic acid (GCA)-which activates EGFR signaling and drives resistance; restoring BSEP enhances BA efflux and resensitizes cells and tumors to TKIs. Mechanistic assays revealed that ursodeoxycholic acid (UDCA) upregulated BSEP and reversed resistance via an FXR-independent mechanism: UDCA directly binds cortactin (CTTN), reduces its PRMT1-dependent mono-methylation, and promotes CTTN degradation via chaperone-mediated autophagy (CMA), thereby enabling YY1 nuclear translocation and transcriptional activation of BSEP. Clinical specimen analyses corroborated an inverse BSEP-CTTN relationship and UDCA modulation. These findings identify impaired BSEP-mediated BA efflux and GCA accumulation as metabolic features of TKI resistance and support targeting the CTTN/YY1/BSEP axis, including UDCA, to overcome resistance.

In colorectal cancer liver metastases, chromosomal instability (CIN) serves as a critical hallmark linked to tumor aggressiveness and poor prognosis. This study integrated single-cell RNA sequencing, weighted gene co-expression network analysis, and non-negative matrix factorization to construct a comprehensive CIN index, revealing that CIN-high tumor cells exhibit more aggressive phenotypes and reside in an immune-excluded tumor microenvironment. Cancer-associated fibroblasts (CAFs) showed enhanced communication with CIN-high tumor cells, and a key CAF-derived gene, CCDC3, was experimentally validated to promote metastasis, proliferation, and CIN in vitro and in vivo. The bio-knowledge graph analysis based on artificial intelligence further revealed the core regulation of CCDC3 in chromosomal instability and liver metastasis of colorectal cancer. Mechanistically, CCDC3 physically interacts with CXCR3 on CRC cells, activating STAT3 phosphorylation and subsequent CDT1 transcription, forming a CCDC3/CXCR3/STAT3/CDT1 signaling axis. Disruption of this axis—either by genetic knockdown or pharmacological inhibition—significantly suppressed metastatic traits, tumor growth, and liver colonization in mouse models. Clinically, high CCDC3 expression correlated with elevated CIN signatures and worse patient survival. These findings uncover a novel CAF-driven signaling pathway that promotes CIN and metastatic progression in CRC, highlighting its potential as a therapeutic target for aggressive, CIN-high colorectal cancer.

In this single-arm, phase 2 study, we explored the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) combined with anlotinib and TQB2450 (an anti-PD-L1 antibody) as a postoperative adjuvant treatment in patients at high risk of hepatocellular carcinoma (HCC) recurrence. Patients with high-risk recurrence of HCC were treated with HAIC, anlotinib (4 or 8 cycles), and TQB2450 after curative surgery. The primary endpoint was disease-free survival (DFS), and the secondary endpoints included overall survival (OS) and safety. 77 patients who met the inclusion criteria were enrolled: 38 in the 4-cycle cohort and 39 in the 8-cycle cohort. As of the data cutoff on June 24, 2024, the median follow-up period was 21.19 months (95% confidence interval [CI], 20.49-21.89). The median DFS and OS of all patients were not reached. 1-year and 2-year DFS rates were 84.4% and 65.8%, respectively, while 1-year and 2-year OS rates were 96.1% and 89.8%, respectively. No significant differences in DFS and OS were observed in patients treated with 4 or 8 cycles of anlotinib. The incidence of grade 3/4 adverse events (AEs) was 28.6%. Postoperative adjuvant HAIC combined with anlotinib and TQB2450 demonstrated encouraging clinical benefits in reducing recurrence with manageable toxicities in patients at high risk of HCC recurrence. 4-cycle anlotinib combined with HAIC and TQB2450 is recommended as an adjuvant treatment for further investigation.

Focal cortical dysplasia type II (FCDII) is a major cause of drug-resistant epilepsy, but genetic factors explain only some cases, suggesting other mechanisms. In this study, we conduct a molecular analysis of brain lesions and adjacent areas in FCDIIb patients. By analyzing over 217,506 single-nucleus transcriptional profiles from 15 individuals, we find significant changes in smooth muscle cells (SMCs) and astrocytes. We identify abnormal vascular malformations and a unique type of SMC that we call "Firework cells", which migrate from blood vessels into the brain parenchyma and associate with VIM+ cells. These abnormalities create localized ischemic-hypoxic (I/H) microenvironments, as confirmed by clinical data, further impairing astrocyte function, activating the HIF-1α/mTOR/S6 pathway, and causing neuronal loss. Using zebrafish models, we demonstrate that vascular abnormalities resulting in I/H environments promote seizures. Our results highlight vascular malformations as a factor in FCDIIb pathogenesis, suggesting potential therapeutic avenues.

489 Background: Immune checkpoint inhibitors plus chemotherapy had demonstrated important therapeutic advantages in biliary tract cancers (TOP-AZ and Keynote-966). At present the data of gallbladder carcinoma (GBC) is in blank condition almost, and the effectiveness remains to be improved. Further, the addition of bevacizumab to PD-1 inhibitors has improved the clinical results in carcinomas, such as hepatocellular carcinoma, for which therapeutic options have been limited. This study intended to explore the safety and efficacy of sintilimab combined bevacizumab with chemotherapy in the first-line treatment of initially unresectable GBC. Methods: The study was an ongoing open-label, single-arm, phase II trial (Clinical Trial ID: NCT05757336), which consisted of 2 parts: safety-run-in part, where pts received sintilimab (200mg/kg, iv, d1, Q3W) + bevacizumab (7.5mg/kg, iv, d1, Q3W) + gemcitabine (1000mg/m2, iv, d1, Q3W) and albumin-bound paclitaxel (125mg/m2, iv, d1, Q3W), followed by experimental part to evaluate the efficacy and safety of this strategy. The primary endpoint was safety and objective response rate (ORR) assessed by RECIST v1.1. Secondary objectives included disease control rate (DCR), progression free survival (PFS) and overall survival (OS). Results: No DLT was reported at safety-run-in part. Up to the end of Sept 2023, 15 patients were enrolled with a median age of 60.4 years (range 46-75), 26.7% were male. Median follow-up time was 3.68 months. All patients completed at least one tumor response evaluation, confirmed ORR was 60.0% and DCR was 93.3%. Median PFS and OS was not reached yet. Grade 3 TRAEs occurred in 40.0% of patients (n=6), and the most common TRAEs (incidence≥5%) among them were rash (20.0%), AST elevation (6.7%), fever (6.7%), platelet count decreased (6.7%), fatigue (6.7%), pneumonitis (6.7%). Conclusions: The combination of sintilimab, bevacizumab and AG chemotherapy was tolerable and showed a promising ORR in initially unresectable GBC patients. This regimen could be a feasible and safe option for initially unresectable GBC, but this needs further validation. Clinical trial information: NCT05757336 .

The relative risk and benefits of Laparoscopic liver resection (LLR) are still controversial. This study aimed to evaluate perioperative and survival outcomes for three primary malignant liver tumors related outcomes following LLR. Data from three Homogeneous-High-Volume-Expert-Centers were collected. Multivariable logistic regression analysis was performed for the association between LLR, and major complications defined as Clavien-Dindo Classification grade >= II. Multivariable Cox proportional hazards regression was used to explore the impact of LLR on primary malignant liver tumor survival. Overall, 5886 patients underwent liver resection, of which 1991 underwent LLR. After adjusting for covariables, LLR had significantly lower rate of CDC grade >= II (OR = 0.56, 95% CI: 0.48-0.67, P < 0.001). Interaction analysis showed that LLR had significant association with sex, drinking status, history of abdominal surgery, and platelet count (all P < 0.05). The overall survival for each primary malignant liver tumor shown potential risk but without significantly different between LLR and OLR (all P > 0.05). LLR was associated with lower rate of major complications, especially in women, non-drinkers, those without a history of abdominal surgery, and those with normal platelet. For primary malignant liver tumors, the survival outcomes did not differ significantly between LLR and OLR.

Hepatocellular carcinoma (HCC) is a type of liver cancer that is associated with high mortality rates. This study aims to investigate the role of ZNF655, a member of the zinc finger protein family, in the development of HCC. Immunohistochemical staining analysis was conducted to evaluate the expression of ZNF655 in HCC patient samples. Lentivirus-mediated ZNF655 knockdown was established in HCC cell lines (BEL-7402 and HCCLM3). The effects of ZNF655 on different aspects of HCC cell behavior such as proliferation, apoptosis, cycle, migration and tumor formation were examined. Downstream targets of ZNF655 in HCC were identified and verified through loss/gain-of-function experiments. Clinically, ZNF655 expression was elevated in HCC and increased with the severity of the disease. Functionally, inhibition of ZNF655 expression reduced the progression of HCC cells by decreasing proliferation, causing apoptosis, arresting cell cycle retention in G2, suppressing migration, and attenuating tumor formation in mice. Mechanistically, the proteasome subunit beta type-8 (PSMB8) was found to be co-expressed with ZNF655 in HCC, and PSMB8 knockdown weakened the promotion of ZNF655 overexpression on HCC. In summary, these findings suggest that ZNF655 promotes the progression of HCC through PSMB8, and inhibition of its expression may be a promising therapeutic target for HCC.

Abstract Purposes: To compare the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) combined with tyrosine kinase inhibitors (TKIs) and anti-programmed cell death protein-1 (PD-1) immunotherapy versus combination therapy of transarterial chemotherapy (TACE), TKIs and PD-1 inhibitors in the treatment for hepatocellular carcinoma (HCC). Methods: The data of 302 patients with HCC receiving HAIC combined with TKIs and PD-1 inhibitors (HAIC-TP group) and 446 patients receiving TACE combined with TKIs and PD-1 inhibitors (TACE-TP group) were retrospectively collected. The progression-free survival (PFS), overall survival (OS), tumor response and adverse events were compared between two groups. Propensity-score matching (PSM) analysis were utilized to minimize the bias. Results: HAIC-TP group exhibited longer PFS (17.1 months versus 8.9 months, P < 0.001), longer OS (not reached versus 14.3 months, P < 0.001) and better objective response rate (RECIST: 33.1% versus 7.8%, P < 0.001; mRECIST: 51.4% versus 17.5%, P < 0.001) than TACE-TP group. Nausea, diarrhea and abdominal pain were more frequent in the HAIC-TP group, while liver dysfunction occurred more common in the TACE-TP group. PSM analysis showed the same results. Conclusions: In patients with HCC, the combination of HAIC with TKIs and anti-PD-1 immunotherapy is an effective and safe therapeutic regimen over TACE-based combination therapy. A prospective study with a large sample size is needed to validate the efficacy and safety of the combination therapy.

Background:Most patients with hepatocellular carcinoma (HCC) are not candidates for liver resection. We investigated the clinicopathological characteristics and prognosis of patients with initially unresectable HCC who underwent hepatectomy after conversion therapy with hepatic arterial infusion chemotherapy (HAIC), tyrosine kinase inhibitors (TKIs), and anti-PD-1 antibodies.Materials and Methods:Patients with initially unresectable HCC who received HAIC combined with TKIs and anti-PD-1 antibodies followed by hepatectomy between December 2020 and December 2022, were retrospectively analyzed. Patient characteristics, tumor characteristics, treatment efficacy, perioperative characteristics, pathological characteristics, and survival outcomes were summarized and analyzed.Results:67 patients were enrolled in this study. Patients were treated with 3 sessions (range:2-6 sessions) of combination therapy and were performed with hepatectomy in 4 months (range:1.4-17.8 months) after the initiation of the combination therapy. The median size of tumor shrinkage was 4.7 cm (range:0.9-11.7 cm). A pathological complete response (pCR) was achieved in 34.3% of the patients (n = 23). The median recurrence-free survival (RFS) was 19.3 months and the median overall survival (OS) was 28.7 months. Patients who achieved pCR had a better RFS (P = 0.004) and those without microscopic vascular invasion (MVI) had a better prognosis (RFS, P = 0.011; OS, P = 0.023). Multivariable logistic analysis revealed that the tumor number was associated with pCR.Conclusion:Hepatectomy after conversion therapy with HAIC, TKIs, and anti-PD-1 antibodies is a feasible treatment strategy for patients with unresectable HCC. This treatment strategy is associated with a promising prognosis.

Background and purposeTo study the changes of corticocerebral hemodynamics in surgical area and postoperative hyperperfusion syndrome in patients with chronic internal carotid artery occlusion (CICAO) by intraoperative indocyanine green videoangiography (ICGA)-FLOW 800 and CT perfusion after superficial temporal artery (STA)–middle cerebral artery (MCA) bypass surgery.MethodsFrom October 2019 to January 2021, 77 patients diagnosed with CICAO underwent direct bypass surgery at Huadong hospital (affiliated with Fudan University) were enrolled. Regions of interest (ROIs) at STA, proximal MCA (PMCA), distal MCA (DMCA), cortical blood capillary (CBC), and cortical vein (CV) were identified after anastomosis by ICGV-FLOW 800 including peak fluorescence intensity (PFI), time to peak (TTP), and area under the time curve (AUC) of fluorescence intensity. All patients underwent perfusion-weighted CT before bypass surgery and those patients with HPS were verified by CTP after bypass.Results14 patients with HPS were verified by perfusion-weighted CT after bypass. In HPS group, the AUCTTP of DMCA was significantly larger (T = −3.301, p = 0.004) and TTP of CBC was shorter (T = −2.929, p = 0.005) than patients in non-HPS group. The larger AUCTTP of DMCA (OR = 3.024, 95%CI 1.390–6.578, p = 0.0050) was an independent risk factor by further multivariate logistic regression analysis.ConclusionThe hemodynamic changes of cortical vessels during STA-MCA bypass surgery could be recorded accurately by ICGV-FLOW 800. Furthermore, the increased AUCTTP of DMCA and shorter TTP of CBC may be potential risk factors of HPS.

Introduction: Treatment of anterior cerebral artery (ACA) aneurysms is still not well established. The Leo stent with blood flow direction is a retrievable stent for intracranial aneurysms, whereas it needs to be studied clearly in patients with ACA aneurysms. Methods: Consecutive patients with ACA aneurysms were retrospectively enrolled in three neurosurgical centers between January 2016 and October 2021. The data on demographics, aneurysm characteristics, symptom resolution, and postoperative course were collected and analyzed. The aneurysm occlusion status was appraised by Raymond-Ray Occlusion Class (RROC). Results: A total of 57 patients with ACA aneurysms were included in our study. Immediate postprocedural angiograms showed that 20 aneurysms (35.1%) were in complete occlusion (RROC 1), 26 aneurysms (45.6%) were in near-complete occlusion (RROC 2), 11 aneurysms (19.3%) were in incomplete occlusion (RROC 3). The angiographic follow-up found that the rate of complete occlusion increased to 57.9%, and near-completion and incomplete occlusion dropped to 29.8% and 12.3%, respectively. The angiographic result of the last follow-up improved significantly (Z=- 2.805, P=0.005). Univariate analysis indicated that distal location of aneurysms (Z=4.538, P=0.033) and ruptured aneurysms (χ2=.6120, P=0.032) were potential risk factors for intra-parent artery narrowing. Furthermore, multivariate logistic regression analysis found that A3 aneurysms (95% CI 1.427~32.744, P=0.016) are the key risk factor for intra-parent artery narrowing. Conclusions: The Leo stent is safe and effective for aneurysms located in ACA circulations. The overall occlusion degree improved during follow-up. A distal, small artery was the risk factor for intra-parent artery narrowing.

Background:The combination of tyrosine kinase inhibitors (TKIs) and anti-PD-1 antibodies with hepatic arterial infusion chemotherapy (HAIC) or transarterial chemoembolization (TACE) has shown encouraging anti-tumor effects in the treatment of hepatocellular carcinoma (HCC). We explored the efficacy and safety of TKIs and anti-PD-1 antibodies combined with HAIC or TACE in HCC. Methods:Data from 302 HCC patients receiving HAIC combined with TKIs and anti-PD-1 antibodies (HAIC-TP group) and 446 HCC patients receiving TACE combined with TKIs and anti-PD-1 antibodies (TACE-TP group) were retrospectively collected. Clinicopathological characteristics, tumor response, progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were compared between two groups. Propensity score matching (PSM) analysis was performed to minimize bias. Results:The HAIC-TP group exhibited better objective response rate (RECIST: 33.1% versus 7.8%, P < 0.001; mRECIST: 51.4% versus 17.5%, P < 0.001), longer PFS (12.4 months versus 8.2 months, P < 0.001), and longer OS (not reached versus 13.8 months, P < 0.001) than TACE-TP group. Surgery was performed after combination therapy in 34 patients of the HAIC-TP group and in 7 patients of the TACE-TP group (P < 0.001). Similar results were also observed in the PSM analysis. Multivariate analysis indicated type of treatment, alpha-fetoprotein, ALBI grade, portal vein tumor thrombus, and extrahepatic status were risk factors for poor prognosis. Nausea, vomiting, diarrhea, and abdominal pain occurred more frequently in the HAIC-TP group, whereas liver dysfunction occurred more frequently in the TACE-TP group. All AEs were acceptable and manageable as a result of treatment interruption or dose modification. Conclusion:The combination of HAIC with TKIs and anti-PD-1 antibodies is an effective and safe therapeutic regimen over TACE-based combination therapy for patients with HCC. A prospective study with a large sample size is required to validate the efficacy and safety of the combination therapy.

BACKGROUND:Cuproptosis is a recently discovered mechanism of programmed cell death caused by intracellular aggregation of mitochondrial lipoylated proteins and destabilization of iron-sulfur proteins triggered by copper. Hepatocellular carcinoma (HCC) is a common malignant tumor with a poor prognosis. We aimed to predict the survival of patients with HCC using the cuproptosis-related gene (CRG) expression.METHODS:We analyzed the expression, methylation, and mutation status of CRGs in 538 HCC patients and correlated the date with clinical prognosis. HCC patients were divided into two clusters based on their CRG expression. The relationship between CRGs, risk genes, and the immune microenvironment was analyzed using the CIBERSORT algorithm and the single-cell data analysis method. A cuproptosis risk model was constructed according to the five risk genes using the LASSO COX method. To facilitate the clinical applicability of the proposed risk model, we constructed a nomogram and conducted an antineoplastic drug sensitivity analysis.RESULTS:Our results suggest that the expression levels of CRGs in HCC are regulated by methylation. The prognoses were significantly different between the patients of the two clusters. The prognostic risk score positively correlated with memory T cell activation and negatively correlated with natural killer (NK) and regulatory T cell activation.CONCLUSION:Our findings indicate the involvement of CRG regulation in HCC and provide new insights into prognosis assessment. Drug sensitivity analysis predicted drug candidates for the treatment of patients with different HCC subtypes.

IMPORTANCE Because of tumor heterogeneity, traditional clinical variables remain insufficient to predict recurrence, which impairs long-term survival among patients undergoing radical hepatectomy for hepatocellular carcinoma (HCC). Vessels encapsulating tumor clusters (VETC) constitute a novel vascular pattern distinct from microvascular invasion (MVI), representing biological aggressiveness of HCC. OBJECTIVE To establish a model to estimate individualized recurrence-free survival (RFS) in HCC by integrating VETC and MVI. DESIGN, SETTING, AND PARTICIPANTS This prognostic study included 498 patients undergoing radical hepatectomy for HCC from 5 academic centers in China from January 1, 2013, to December 31, 2016, and consisted of 3 cohorts training (243 [48.8%]), internal validation (122 [24.5%]), and external validation (133 [26.7%]). Follow-up was completed on March 30, 2020, and the data were analyzed from December 1 to 31, 2020. EXPOSURES VETC, MVI, tumor number, and maximum tumor size. MAIN OUTCOMES AND MEASURES The primary end point was RFS. The risk score for relative recurrence and nomogram for absolute RFS probability were derived from the final model, which contained variables recommended by multivariate least absolute shrinkage and selection operator Cox proportional hazards regression analysis. Their performance was quantified using the Harrell concordance index (C index), the time-dependent area under the receiver operating characteristic curve, and calibration curves and was compared with 6 prognostic systems. Recurrence-free survival was estimated by the Kaplan-Meier method, and RFS curves were compared using a log-rank test. RESULTS Among the 498 patients, 432 (86.7%) were men; the mean (SD) age at diagnosis was 51.4 (11.3) years. Independent predictors for RFS identified included VETC, MVI, tumor number, and maximum tumor size, which were incorporated into the multivariate model (VMNS model). The C index (0.702; 95% CI, 0.653-0.752) for the VMNS score of the training cohort was significantly higher than those of 6 conventional systems (0.587 [95% CI, 0.535-0.638] to 0.657 [95% CI, 0.606-0.708]). Different recurrence risk groups defined by the VMNS score showed significantly different 2-year RFS (low-risk group, 81.4% [SE, 0.036]; medium-risk group, 62.1% [SE, 0.054]; high-risk group, 30.1% [SE, 0.079]; P < .001). Calibration curves of the VMNS nomogram showed good agreement between the nomogram-predicted RFS probability and actual RFS proportion. The internal and external validation cohorts confirmed the results. CONCLUSIONS AND RELEVANCE The VMNS model enabled individualized prognostication of RFS in patients with HCC undergoing curative resection.

The lymphocyte-C-reactive protein ratio (LCR) is a recently described inflammation-based score, and it remains unclear which is the optimal inflammation-based score among patients with hepatocellular carcinoma (HCC) who underwent transarterial chemoembolization (TACE). A large cohort of HCC patients (n=1625) who underwent TACE as the initial treatment were enrolled in the present study. Inflammation-based scores, including the Glasgow Prognostic Score (GPS), modified Glasgow Prognostic Score (mGPS), high-sensitivity modified Glasgow Prognostic Score (Hs-mGPS), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), prognostic nutritional index (PNI), systemic immune-inflammation index (SII), and LCR, were all related to the survival of HCC patients, but only the LCR score was a significant and independent predictor in multivariate analysis (hazard ratio: 1.45; 95% confidence interval: 1.27-1.65; P<0.001). Further analysis showed that the LCR score stably and consistently differentiated subgroup patients with distinct prognoses. The predictive accuracies of the LCR score (0.70, 0.68, and 0.68 for 1-, 3-, and 5-year C-index, respectively) were superior to the other inflammatory-based scores (0.60-0.64, 0.58-0.62, and 0.58-0.62 for 1-, 3-, and 5-year C-index, respectively). The LCR score was an independent prognostic indicator for HCC patients who underwent TACE, and it was superior to the other inflammation-based scores in prognostic ability.

RNA-binding motif protein 25 (RBM25) is a poorly characterized RNA-binding protein that is involved in several biological processes and regulates the proliferation and metastasis of tumor cells. The regulatory role of RBM25 in hepatocellular carcinoma (HCC) is unknown. Here, RBM25 expression and outcomes in HCC patients were evaluated using The Cancer Genome Atlas database. RBM25 was overexpressed in HCC patients compared with the healthy group. The high expression of RBM25 in tumor tissues was significantly related to poor overall survival (P<0.001). Overexpression of RBM25 significantly contributed to poorer survival in male patients and N0 stage patients (P<0.001). Spearman analysis and weighted gene co-expression network analysis identified 694 RBM25-related genes. Protein-protein interaction network analysis revealed the Cluster with the highest score, which positively correlated with RBM25. CDCA5 and INCENP were identified as the core functional genes related to RBM25. The overexpression of CDCA5 and INCENP in HCC patients was examined using the Human Protein Atlas database. The findings collectively indicated that RBM25 may interact with CDCA5 and INCENP to regulate HCC. Our detailed characterization of RBM25 protein interactions and related core functional genes provides a basis for further studies aimed at identifying molecular regulatory pathways or splicing events.

PURPOSE:This study aimed to evaluate the prognostic value of the lymphocyte-C-reactive protein ratio (LCR) score, a novel inflammation-based score based on lymphocytes and C-reactive protein, in hepatocellular carcinoma (HCC) patients treated with curative intent.PATIENTS AND METHODS:A total of 1158 HCC patients undergoing surgical resection or radiofrequency ablation with curative intent were recruited from 3 different centres and divided into a primary cohort (n=716) and a validation cohort (n=442). Univariate and multivariate analyses were performed to identify variables associated with overall survival (OS). The discriminatory accuracy of seven inflammation-based scores was compared by using the concordance index (C-index).RESULTS:The LCR score differentiated HCC patients into two groups with distinct prognoses (1-, 3-, and 5-year OS rates and median OS: 92.9%, 81.9%, 73.3% and 99.2 months and 79.8%, 56.6%, 49.7% and 69.1 months; P<0.001). Multivariate analysis showed that LCR score, AFP, ALBI score, tumour size, and TNM stage were independently associated with OS. When patients were stratified according to different disease states, the LCR score could still differentiate HCC patients into two groups with distinct prognoses (all P<0.005). The LCR score demonstrated a markedly superior C-index of 0.621 compared with the other inflammation-based scores (0.503-0.590). These findings were supported by the validation cohort.CONCLUSION:The preoperative LCR score is a novel, stable, and clinically feasible prognostic marker for patients with HCC, independent of liver function, tumour characteristics, and treatment allocation and is superior to other inflammation-based scores in terms of its prognostic ability.

PURPOSE:It remains unknown which staging system is best in predicting the survival of patients with intermediate stage hepatocellular carcinoma (HCC). We aimed to investigate the performance of nine currently used HCC staging systems.PATIENTS AND METHODS:Between 2005 and 2014, a large cohort of 880 consecutive patients with intermediate stage HCC and sufficient data for utilization in all staging systems were enrolled. The prognostic performance of each staging system was compared. Independent prognostic variables were also identified.RESULTS:Multivariate analysis revealed that alkaline phosphatase (ALP), aspartate aminotransferase (AST), etiology, alpha-fetoprotein (AFP), Child-Pugh stage, tumor size, and tumor number were independent prognostic factors for survival. In the entire cohort, the Hong Kong Liver Cancer (HKLC) staging system was associated with the highest Harrell's c-index and lowest Akaike information criterion value in comparison with other systems. In subgroup analysis according to treatment strategy, the HKLC staging system remained the best prognostic model in patients undergoing hepatic resection (n=222) or transarterial chemoembolization (n=658). Additional prognostic factors of AST, ALP, etiology, and AFP improved the discriminatory ability of HKLC.CONCLUSION:The HKLC staging system is stable and consistently the best prognostic model in all patients with intermediate-stage HCC and in patients subjected to different treatment strategies. Selecting an optimal staging system is helpful in improving the design of future clinical trials in intermediate stage HCC.

BACKGROUND:The role of surgery in breast cancer liver metastases (BCLM) remains elusive, and current application is limited. Our aim is to investigate whether hepatic resection (HR) of BCLM improves survival compared with non-hepatic resection (NHR) treatment.METHODS:Three hundred and eighty-four patients with BCLM from 2008 to 2018 were divided into two groups. Propensity score matching (PSM) analysis was used to compare the clinical outcomes.RESULTS:After PSM the mean overall survival (OS) and the 1, 3, and 5-year OS rates in HR group were 61.8 months, 92.6%, 54.7% and 54.7%, respectively; while for NHR group these values were 38.6 months, 79.2%, 45.6% and 21.9%, respectively (p < 0.007). Multivariate analysis indicated hormonal receptor status (p = 0.039) and hepatic resection (p = 0.032) were independent prognostic factors.CONCLUSION:Our study revealed that hepatectomy yields a survival benefit safely compared with medical treatments, especially for patients with positive hormonal receptors.