3028 Background: Pts with advanced HCC face limited treatment options beyond immunotherapy and anti-angiogenic agents. GPC3, a surface antigen overexpressed in HCC and associated with poor prognosis, represents a promising therapeutic target due to its tumor-specific expression. MRG006A, a potential first-in-class GPC3-targeted ADC, demonstrated potent pre-clinical anti-tumor activity. Here we report the preliminary safety and efficacy of MRG006A in advanced HCC with intermediate/high GPC3 expression from a phase I/II trial. Methods: MRG006A-001 (NCT07093970) is an ongoing first-in-human, open-label, multi-center phase I/II study. The phase I study comprises dose escalation (Ia) and dose optimization/expansion (Ib) stages. The dose-escalation employed an accelerated titration plus 3+3 design. Eligible pts who had failed standard treatment received MRG006A intravenously at 1.6-6.4 mg/kg every three weeks (Q3W). GPC3 expression was only required for dose expansion cohorts. The primary endpoints were safety and tolerability. Secondary endpoints included objective response rate (ORR), disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), clinical benefit rate (CBR), etc. Results: As of Dec 19, 2025, the maximum administered dose was established as 6.4 mg/kg Q3W, with ≥ G3 treatment-related adverse event (TRAE) of platelet count decreased reported in all six pts at this dose level and dose-limiting toxicity (G4 platelet count decreased) observed in one patient. During dose escalation, tumor response was observed at 3.2 mg/kg and 4.8 mg/kg. Accordingly, dose optimization in phase Ib proceeded with three levels (3.2, 4.0, and 4.8 mg/kg Q3W). Twenty-six HCC pts with intermediate or high GPC3 expression were enrolled across three cohorts; 61.5% had BCLC stage C disease; median 2 (range 1-4) prior lines of therapy, and 25 (96.2%) had received immune checkpoint inhibitors and anti-angiogenic agents. Among 25 efficacy evaluable pts, ORR, DCR and CBR were 23.1%, 68.0% and 32.0%, respectively. In pts with high GPC3 expression (n=12), ORR, DCR and CBR increased to 33.3%, 75.0% and 50.0%, respectively; median PFS and DOR were 7.0 and 4.2 months (median follow-up 5.7 months). Most pts (24 [92.3%]) experienced TRAE of any Grade. TRAEs of ≥ G3 were reported in 11 (42.3%) pts . The most common TRAEs were platelet count decreased (88.5%), blood bilirubin increased (50.0%), AST increased (46.2%), white blood cell count decreased (38.5%), and nausea (30.8%). No treatment-related permanent discontinuations or deaths occurred. Conclusions: MRG006A demonstrated manageable safety and promising anti-tumor activity in heavily pretreated pts with GPC3-expressing advanced HCC. Our findings support the therapeutic potential of GPC3-directed ADC and merits further clinical investigations. Clinical trial information: NCT07093970 .

4148 Background: Immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 have demonstrated efficacy in aHCC. Despite improved outcomes with PD-1/PD-L1 inhibitor-based regimens, prognosis remains poor and there is a continued unmet need for alternative therapies with long-term survival benefits. This study aimed to evaluate the effectiveness and safety of IBI310 (anti-CTLA-4 antibody) combined with sintilimab (anti-PD-1 antibody) in the first-line treatment of aHCC. Methods: Pts were randomized in a 2:1 ratio to IBI310+sintilimab group or sorafenib group. The experimental group received IBI310 3mg/kg intravenously (IV) and sintilimab 200 mg IV on day 1 of every 3 weeks. The control group received sorafenib 400 mg orally twice daily (BID) continuously until disease progression, intolerable toxicity, death or other protocol-specified discontinuation criteria. During the study, the IBI310 dose was adjusted to 1 mg/kg every 6 weeks. Primary end points included overall survival (OS) and objective response rate (ORR)assessed by the independent radiology review committee (IRRC) per RECIST v1.1. Secondary endpoint included progression-free survival (PFS), disease control rate (DCR), safety, etc. Results: As of August 2022, 344 patients were enrolled and allocated to Group 1 (G1, IBI310 3mg/kg + sintilimab, n=84), Group 2 (G2, modified-dose IBI310 1mg/kg + sintilimab, n=145) and Group 3 (G3, sorafenib, n=115). Overall, PFS and ORR improved with IBI310+sintilimab vs Sorafenib. The median OS in the primary endpoint was 44.0 months(G1), 36.1 months(G2) and 22.9 months(G3), respectively. Confirmed ORRs were significantly higher in the combination therapy groups (G1: 41.7%; G2: 22.1%) versus the control group (2.6%). Median PFS of three groups were 13.5 months(G1), 6.1 months(G2) and 2.8 months(G3), respectively. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 60.7% (G1), 34.7% (G2), and 35.1% (G3) of patients. Conclusions: Compared with sorafenib group, combination treatment of IBI310 + sintilimab as first-line treatment demonstrated survival benefits and a manageable safety profile in aHCC. Clinical trial information: NCT04720716 . Survival data. IBI310(3mg/kg)+Sintilimab(N=84) IBI310(1mg/kg)+Sintilimab(N=145) Sorafenib(N=115) mOS, m 44.0 36.1 22.9 Confirmed ORR, n(%) 35(41.7) 32(22.1) 3(2.6) mPFS, m 13.5 6.1 2.8

ObjectiveOur previous study found that the combined prealbumin and lymphocyte (Co-PaL) score could accurately classify patients into severe, mild to moderate malnutrition and good nutrition, and might be a predictor for prognosis of patients undergoing gastrectomy for stage II/III gastric cancer (GC). The aim of the present study was to validate these findings.MethodsThe medical records of stage II/III GC patients undergoing curative resection in our hospital from January, 2017 to December, 2023 were retrospectively reviewed. Basing on whether the lymphocyte count was <1.5 ×109/L and/or the prealbumin concentration <180 mg/L, patients were assigned a Co-PaL score of 0, 1 or 2, respectively. A nomogram was established basing on independent predictors for OS identified by univariate and multivariate Cox regression analyses. Concordance index and calibration curves were used to evaluate the nomogram. Clinical utility and predictive accuracy were further assessed by net reclassification index (NRI), integrated discrimination improvement (IDI) and decision curve analysis (DCA).ResultsA total of 890 consecutive patients were recruited. Multivariate regression analyses revealed that Co-PaL score, TNM stage, post-operative complications and adjuvant chemotherapy were independent predictors for OS. A nomogram based on these four variables was established. The C-index value obtained for the model was 0.701 (95%CI: 0.672-0.729). The area under the curve (AUC) values to predict the 1- 3- and 5-year survival probabilities were 0.709 (95%CI: 0.662-0.756), 0.728 (95%CI: 0.692-0.764) and 0.734 (95%CI: 0.695-0.7772), respectively. The calibration curves represented fine consistency between the actual and predicted 1-, 3- and 5-year survival probabilities. Compared with TNM staging system, our model demonstrated strong accuracy, discriminative ability, and clinical utility.ConclusionsThe Co-PaL score was a simple and promising predictor for prognosis of patients undergoing gastrectomy for stage II/III GC. The established nomogram showed superiority over TNM staging system in predicting OS.

1. Valproic acid (VPA) has great individual differences in clinical efficacy, the study aimed to investigate the effects of VPA-related pharmacogenomics on its antiepileptic efficacy, providing evidence for clinical rational drug use. 2. The patients were followed up for one year, and the number of seizures within one year was used as the evaluation index of efficacy. The target SNPS were genotyped by SNP scan method. 3. A total of 253 patients with epilepsy treated with valproate monotherapy were enrolled in this study, including 125 patients in the valproate-sensitive group and 128 patients in the valproate-resistant group. χ2 Test showed that the frequency of C allele of CACNA1H rs3751664 in valproate-sensitive group was significantly higher than that in valproate-resistant group (93.6% vs. 87.5%, p = 0.023), and the difference was still statistically significant after adjusting for confounding factors by logistic regression analysis (p = 0.037). Haplotype analysis showed no association between gene polymorphisms and efficacy of valproic acid. 4. CACNA1C rs1051375 GG and GA genotype patients have a lower risk of drug resistance than AA genotype patients, CACNA1H rs3751664 T allele is a risk factor for VPA monoresistance, while APEH rs3816877 CT genotype patients have a trend of drug resistance during VPA treatment.

4093 Background: Combination of an anti-PD-1/L1 antibody with an anti-angiogenic agent is currently the preferred 1L treatment for aHCC. Addition of a CTLA-4 inhibitor may further improve anti-tumor activity, with complementary immunostimulatory effects from CTLA-4 and PD-1/L1 blockade. We conducted a multicenter, open-label, phase 1b/2 trial (NCT05444088) to assess SHR-8068, a novel anti-CTLA-4 monoclonal antibody (mAb), combined with adebrelimab (A, anti-PD-L1 mAb) and bevacizumab (B) in patients (pts) with aHCC. Methods: Pts with or without prior treatment were enrolled (phase 1b: failed or refused standard therapy; phase 2: ≤1L systemic therapy, no immunotherapy [IO]). SHR-8068 was evaluated in 2 dosing regimens with AB: 1 mg/kg Q6W (Combo 1) or 4 mg/kg priming dose (Combo 2). An additional cohort evaluated AB alone (Combo 3). A was dosed at 20 mg/kg Q3W and B at 15 mg/kg Q3W for all regimens. Results: As of Oct 31, 2024, a total of 27, 53 and 21 pts received Combo 1, 2, and 3, respectively, across 2 study phases (overall: IO naïve, 97.0%; prior anti-angiogenic therapy, 32.7%); median follow-up was 16.7, 11.1 and 11.3 mo, respectively. In pts treated with Combo 2, the objective response rate (ORR) was 47.2% (25/53; 95% CI 33.3%–61.4%), with a median duration of response (DoR) of 12.7 mo (95% CI 5.8–NR). The median progression-free survival (PFS) was 8.7 mo (95% CI 5.5–11.6); median overall survival (OS) was not reached, with a 12-mo OS rate of 76.0% (95% CI 59.3%–86.6%). Numerically improved ORR and survival outcomes were seen with Combo 2 vs Combo 1 and 3 (Table 1). Overall, grade ≥3 treatment-related adverse events (TRAEs) occurred in 55.6%, 41.5% and 42.9% of pts with Combo 1, 2 and 3. The most common grade ≥3 TRAEs (incidence ≥10% for any Combo) were decreased platelet count (22.2%, 5.7%, and 4.8% for Combo 1, 2, and 3) and hypertension (18.5%, 7.5%, and 9.5%, respectively). TRAE led to discontinuation of any study agent in 11.1%, 1.9% and 9.5% of pts, respectively. There was 1 treatment-related death (Combo 3). Conclusions: SHR-8068 combined with adebrelimab and bevacizumab showed promising efficacy and manageable safety in aHCC. A more favorable benefit-risk profile was observed for SHR-8068 given as a priming dose. A phase 3 trial (NCT06618664) is currently underway to further assess the combination as 1L treatment for aHCC. Clinical trial information: NCT05444088 . Efficacy outcomes. Combo 1 (n=27) Combo 2 (n=53) Combo 3 (n=21) ORR, % (95% CI) 29.6 (13.8–50.2) 47.2 (33.3–61.4) 19.0 (5.5–41.9) Median DoR * , mo (95% CI) NR (9.4–NR) 12.7 (5.8–NR) NR (7.0–NR) 9-mo DoR rate * , % (95% CI) 100.0 (NR–NR) 69.8 (41.7–86.3) 66.7 (5.4–94.5) DCR, % (95% CI) 77.8 (57.7–91.4) 77.4 (63.8–87.7) 81.0 (58.1–94.6) Median PFS * , mo (95% CI) 6.9 (2.7–NR) 8.7 (5.5–11.6) 6.7 (2.8–9.5) 12-mo OS rate * , % (95% CI) 70.4 (49.4–83.9) 76.0 (59.3–86.6) 70.8 (46.2–85.7) Tumor response was assessed by investigator per RECIST v1.1. * Kaplan-Meier method. NR, not reached.

e16204 Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, with limited therapeutic options for advanced stages. Camrelizumab, a monoclonal antibody against PD-1, has shown promise in the treatment of unresectable HCC both as monotherapy and in combination with anti-angiogenic tyrosine-kinase inhibitors (TKIs). Real-world data are crucial to assess the performance of camrelizumab-based regimens in routine clinical settings. This study aimed to evaluate the real-world therapeutic outcomes of camrelizumab-based regimens for unresectable HCC. Methods: This multi-center, real-world study included HCC patients diagnosed via pathology or imaging. These participants had been previously treated with camrelizumab-based regimens including camrelizumab monotherapy or combinations with TKIs, chemotherapy, locoregional treatments or other physician-recommended options. Observational data were collected including baseline characteristics, treatment regimens, efficacy and adverse events. The real-world best overall tumor response (rwBOR) was defined as the best results from multiple effectiveness evaluations, reflected in the real-world objective response rate (rwORR) and real-world disease control rate (rwDCR). Results: As of January 3, 2025, 1278 patients treated with camrelizumab-based regimen were evaluable for retrospective analysis. The median age was 57 years (range 19-85) with 28.7% aged ≥ 65 years, and the majority was male (86.9%). The baseline disease stages included 43.9% at China Liver Cancer Staging (CNLC) Ib-IIb, 23.2% at CNLC IIIa, and 32.9% at CNLC IIIb. Elevated AFP level (≥ 400 ng/mL) were observed in 37.9% of patients and 66.4% had Albumin-Bilirubin (ALBI) grade 2 or 3. Moreover, 28.4% had prior anti-tumor treatments. During the follow-up period, rwBOR revealed a rwORR of 29.1% (95% CI: 26.6–31.7) and a rwDCR of 90.8% (95% CI: 89.1–92.3). AFP level decreased as early as the first visit with a mean reduction of –1210.9 ng/mL (±19,697.0). ALBI scores declined from baseline and the proportion of patients with ALBI grade 1 maintained stable at approximately 30.0% throughout the follow-up. Conclusions: Camrelizumab-based regimens exhibited encouraging real-world effectiveness in unresectable HCC patients, achieving enhanced control of tumor progression while preserving liver function throughout the treatment. These findings provide valuable insights into the use of camrelizumab in routine clinical practice and highlight its potential as a foundational therapy for unresectable HCC within real-world patient populations.

BACKGROUND:Immunotherapy combinations have revolutionised the therapeutic landscape of advanced hepatocellular carcinoma (HCC), but not all yield a significant overall survival benefit, underscoring the need for novel effective agents. Anlotinib plus penpulimab has demonstrated encouraging activity and safety in a phase 2 study. In this phase 3 trial, we aimed to assess whether the combination of anlotinib plus penpulimab improved survival versus sorafenib in patients with unresectable HCC. METHODS:APOLLO was a multicentre, open-label, parallel-controlled, randomised, phase 3 trial conducted at 79 centres in China. Patients aged 18-75 years with unresectable HCC, no previous systemic therapy, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 were randomly assigned (2:1) to anlotinib (10 mg orally once daily on days 1-14) plus penpulimab (200 mg intravenously on day 1), or sorafenib (400 mg orally twice daily) every 3 weeks. Randomisation was done centrally using block randomisation with a fixed block size of 3 and stratified by the presence of macrovascular invasion or extrahepatic metastasis, α-fetoprotein concentration, and ECOG performance status. Sex (male or female) and ethnicity (Chinese or other) were self-reported. The co-primary endpoints were progression-free survival assessed by masked independent review committee and overall survival in the intention-to-treat population. Safety was assessed in all participants who received at least one dose of the study drug and had at least one recorded safety assessment. Final progression-free survival and second interim overall survival analyses are presented. This trial is registered at ClinicalTrials.gov, NCT04344158, and follow-up is ongoing. FINDINGS:From Aug 11, 2020, to June 20, 2023, 940 patients were screened for inclusion in the trial, 291 were excluded, and 649 were randomly assigned to an intervention (433 were assigned to the anlotinib plus penpulimab group and 216 were assigned to the sorafenib group. 551 (85%) of the 649 patients were male and 98 (15%) were female. All patients were Chinese with a median age of 57 years (IQR 50-65). For the final analysis of progression-free survival (June 5, 2023), 636 patients (424 patients in the anlotinib plus penpulimab group vs 212 patients in the sorafenib group) comprised the intention-to-treat population. For the second interim analysis of overall survival (Jan 29, 2024), 649 patients (433 vs 216) comprised the intention-to-treat population. Median follow-up was 6·2 months (IQR 5·5-7·5) for the anlotinib plus penpulimab group and 4·2 months (2·9-7·1) for the sorafenib group for final progression-free survival analysis, and 15·3 months (14·3-17·3) for the anlotinib plus penpulimab group and 14·5 months (11·5-17·0) for the sorafenib group for the second interim overall survival analysis. Median progression-free survival was significantly extended with anlotinib plus penpulimab versus sorafenib (6·9 months [95% CI 5·8-8·0] vs 2·8 months [2·7-4·1]; hazard ratio [HR] 0·52 [95% CI 0·41-0·66]; p<0·0001). Median overall survival was significantly prolonged with anlotinib plus penpulimab compared with sorafenib (16·5 months [95% CI 14·7-19·0] vs 13·2 months [9·7-16·9]; HR 0·69 [95% CI 0·55-0·87]; p=0·0014). The most common grade 3 or worse treatment-related adverse events were hypertension (75 [17%] patients in the anlotinib plus penpulimab group vs 22 [10%] in the sorafenib group) and decrease in platelet count (39 [9%] vs 13 [6%]). Treatment-related serious adverse events occurred in 90 (21%) and 19 (9%) patients in the respective groups; treatment-related deaths occurred in one (<1%) patient in the anlotinib plus penpulimab group (upper gastrointestinal haemorrhage) and two (1%) patients in the sorafenib group (hepatic failure and death of unknown cause). INTERPRETATION:Anlotinib plus penpulimab significantly improved progression-free survival and overall survival versus sorafenib in unresectable HCC and might be a new first-line option. These findings require verification in other regions of the world. FUNDING:Chia Tai Tianqing Pharmaceutical Group.

Hua Xiao,1,2 Jia Luo1 1Department of Hepatobiliary and Intestinal Surgery, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, People’s Republic of China; 2Department of Gastroduodenal and Pancreatic Surgery, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, People’s Republic of ChinaCorrespondence: Hua Xiao, Email huakexh2010@163.com

Hilar cholangiocarcinoma (hCCA) is a malignant tumor originating from the epithelial cells of the bile ducts, and it is characterized by an aggressive nature, complex surgical management, high mortality, and poor prognosis. Despite recent advances in surgical techniques, medical devices, and related technologies, there remains a pressing need to standardize diagnostic and therapeutic pathways to improve treatment outcomes and extend long-term patient survival. To better integrate and refine these standards, this consensus was reached through a national conference held in Changsha, Hunan Province, involving multidisciplinary experts from various regions across China. This collaborative effort, drawing from various medical facilities and academic organizations nationwide, resulted in the reaching of the "Chinese Multicenter Expert Consensus on the Diagnosis and Treatment of Hilar Cholangiocarcinoma: 2025 Edition" based on current clinical studies and over 40 years of clinical practice experience in managing hCCA. The consensus provides a comprehensive overview of hCCA, including its epidemiological characteristics, diagnostic and screening methods, pathological features, staging and classification systems, and various treatment modalities, while offering specific and actionable recommendations for clinical practice that highlight well-defined indications for surgical, local, and systemic therapies and that emphasize the importance of multidisciplinary approaches to both diagnostic and therapeutic workflows.

Background To establish a nomogram to predict the probability of survival of patients with stage II/III gastric cancer (GC) who received incomplete peri-operative adjuvant chemotherapy (PAC). Methods The medical records of stage II/III GC patients who received curative resection and 1 to 5 cycles of PAC from two tertiary hospitals were retrospectively reviewed. Patients were randomly classified into either a training group or validation group at a ratio of 7:3. The nomogram was constructed based on various prognostic factors using Cox regression analysis in the training cohort, and was validated by the validation group. Concordance index and calibration curves were used to evaluate the discrimination and calibration of the nomogram. Additionally, decision curve analysis (DCA) was used to compare the net clinical benefits of the nomogram and eighth version of TNM staging system. Results A total of 1,070 consecutive patients were included and 749 patients were enrolled into the training group. Lower body mass index (< 18.5 kg/m 2 ), total gastrectomy, stage III disease and fewer cycles of PAC were identified to be independent predictors for poorer survival. The area under the curve (AUC) values of receiver operating characteristics (ROC) curve predicting 5-year survival probabilities and C-index were 0.768 and 0.742, 0.700 (95%CI: 0.674–0.726) and 0.689 (95%CI: 0.646–0.732) in the training and validation groups, respectively. The calibration curves in the validation cohort showed good agreement between the prediction and observation of 1-, 3- and 5-year survival probabilities. Furthermore, DCA showed that our model has a better net benefit than that of TNM staging system. Conclusions The findings emphasize the value of completing PAC. The nomogram which was established to predict survival probability in patients with stage II/III GC receiving radical gastrectomy and incomplete PAC had good accuracy and was verified through both internal and external validation.

3505 Background: Immune checkpoint inhibitors have been used in neoadjuvant setting and showed promising clinical benefits in various tumors. Herein, we evaluate IBI310 plus sintilimab as neoadjuvant treatment in patients (pts) with microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) colorectal cancer (CRC) in a randomized, open-labeled, phase Ib study. Methods: Previously untreated pts with locally advanced (stage IIB-III), resectable, MSI-H/dMMR CRC were enrolled and randomized to receive 1 cycle of IBI310 1mg/kg plus 2 cycles of sintilimab 200 mg Q3W (arm A) or 2 cycles of sintilimab 200 mg Q3W (arm B) as neoadjuvant treatment. The stratification factors were risk evaluation at baseline (high risk: stage T4 or N2 vs low risk: stage T1-3 and N1) and age ( < 55 years vs ≥55 years). Curative resection was scheduled on day 36 to 56 after first dose of neoadjuvant treatment. Primary endpoint was pathological complete response (pCR) rate. Secondary endpoints included R0 resection rate and safety. Results: As of February 4, 2024, 101 pts were enrolled (males: 55.4%, median age: 56 years, ECOG PS 1: 54.5%, high risk: 76.2%) and randomized into arm A (n = 52) and arm B (n = 49). In arm A, 1 pt had early termination of treatment (withdrawal). In arm B, 4 pts had early termination of treatment (1 withdrawal, 1 died, 2 continued neoadjuvant sintilimab). Scheduled curative resection were performed in 51 (98.1%) pts in arm A and 45 (91.8%) pts in arm B. Postoperative evaluation revealed mismatch repair-proficient (pMMR) in 1 pt each in arm A and arm B. The pCR rates were 80.0% (40/50, 95%CI: 66.3-90.0) in arm A vs 47.7% (21/44, 95%CI: 32.5-63.3) in arm B (p = 0.0007). All pts received surgery had R0 resection. Median time between first dose of neoadjuvant treatment and surgery was 47 days (range: 35-82). Surgery delay occurred in 3 pts including 2 pts in arm A due to grade 2 hypothyroidism (2 days delay) and grade 1 hyperthyroidism (13 days delay), and 1 pt in arm B for other reason (26 days delay). Treatment-emergent adverse events (TEAEs) occurred in 46 pts (88.5%, grade≥3 in 13 pts) in arm A and 39 pts (79.6%, grade≥3 in 9 pts) in arm B. Immune-related adverse events (irAEs) occurred in 22 pts (42.3%) in arm A and 18 pts (36.7%) in arm B. Grade ≥3 irAEs occurred in 3 pts in arm A, including immune-mediated myocarditis, ileus and enteritis, and in 4 pts in arm B, including alanine aminotransferase increased, rash, hypothyroidism and myocarditis. Serious TRAEs occurred in 4 (7.7%) pts in arm A and 3 (6.1%) pts in arm B. TRAE leading to death occurred in 1 pt in arm B (myocarditis). Conclusions: Neoadjuvant IBI310 plus sintilimab significantly improved pCR rate than sintilimab alone in MSI-H/dMMR CRC. The safety profiles were comparable and manageable in both treatment arms. Clinical trial information: NCT05890742 .

Objective: The aim of this study was to investigate the predictive value of peripheral lymphocyte subsets for prognosis of gastric cancer (GC) patients following radical gastrectomy. Methods: Consecutive GC patients received curative resection and examined peripheral lymphocyte subsets in Hunan Cancer Hospital were enrolled as training cohort (n=231), and those from Wuhan Union Hospital and Wuhan Tongji Hospital were included as external validation cohort (n=159). The optimal cutoff values of lymphocyte subsets for overall survival (OS) in training cohort were determined by X-tile. The independent predictive factors for OS were identified using univariate and multivariate Cox regression analyses. Furthermore, the predictive value of lymphocyte subsets were evaluated in validation cohort. Results: The optimal cutoff value of T lymphocytes for OS was 0.84x10(9)/L in the training cohort. Decreased T lymphocyte (<0.84x10(9)/L) were identified as an independent predictor for unfavorable prognosis both in the training and validation cohorts (HR:2.835, 95% CI:1.580-5.087, P<0.001; HR:2.470, 95% CI:1.069-5.711, P=0.034). In the entire cohort, stratified analyses revealed that lower T lymphocyte negatively affected the oncological outcomes in patients with stage II/III disease. A synergistic influence was confirmed in those with decreased T lymphocyte and not received adjuvant chemotherapy (AC). Further analyses revealed that AC significantly prolonged OS in stage II/III patients with decreased T lymphocyte, but not in those with relatively higher T lymphocyte. Conclusion: Peripheral T lymphocyte numbers was a reliable predictor for OS in GC patients undergoing radical gastrectomy. Additionally, T lymphocyte might serve as an indicator for efficacy of AC in stage II/III GC patients.

Microwave ablation (MWA) is widely applied in the treatment of cancer, especially hepatocellular carcinoma (HCC). However, the lack of indicators for evaluating ablation completeness limits the success rate and wider application of MWA. This study therefore aims to identify novel serum biomarkers for evaluating the completeness of ablation. Multiple cytokines are preliminarily identified through cell experiments, and the potential as biomarkers is evaluated using clinical serum samples from patients with HCC before and after MWA. CCL20 and EGF are identified as promising biomarkers of the completeness of MWA. Additionally, we develop a highly sensitive and specific quantitative detection method for detecting CCL20 and EGF levels by fabricating a sandwich surface-enhanced Raman spectroscopy (SERS) nano-architecture amplification-based immunosensor. The linear detection range of this SERS platform is 0.1 pg/mL-1 ng/mL with the limit of detections (LoDs) decreasing to 0.082 pg/mL for CCL20 and 0.096 pg/mL for EGF. The remarkable consistency of the SERS immunosensor and ELISA in detecting CCL20 and EGF serum levels highlights the promising clinical utility of SERS in biomarker detection. The exceptional sensitivity of SERS in detecting CCL20 and EGF offers a potential avenue for enhancing the assessment of clinical MWA completeness, consequently leading to improved patient survival rates.

Liver cancer is a common malignant tumor in the world. The liver cancer in early stage had no specific symptoms. More and more studies have shown that tumor microenvironment（TME） is one important cause for malignant transformation of hepatocytes. Many studies have reported the role of TME in liver cancer. This article mainly summarized the compositions and the role of TME in liver cancer, as well as the targeting therapy for liver cancer microenvironment, so as to help improve the diagnosis, treatment and prognosis of liver cancer, and improve the survival rates of patients with liver cancer.

Although APEX1 is associated with the tumorigenesis and progression of some human cancer types, the function of APEX1 in gallbladder cancer (GBC) is unclear. In this study, we found that APEX1 expression is up-regulated in GBC tissues, and APEX1 positive expression is related to aggressive clinicopathological features and poor prognosis of GBC. APEX1 was an independent risk factor of GBC prognosis, and presented some pathological diagnostic significance in GBC. Furthermore, APEX1 was overexpressed in CD133+ GBC-SD cells in comparison with GBC-SD cells. APEX1 knockdown increased the sensitivity of CD133+ GBC-SD cells to 5-Fluorouracil via facilitating cell necrosis and apoptosis. APEX1 knockdown in CD133+ GBC-SD cells dramatically inhibited cell proliferation, migration, and invasion, and promoted cell apoptosis in vitro. APEX1 knockdown in CD133+ GBC-SD cells accelerated tumor growth in the xenograft models. Mechanistically, APEX1 affected these malignant properties via upregulating Jagged1 in CD133+ GBC-SD cells. Thus, APEX1 is a promising prognostic biomarker, and a potential therapeutic target for GBC.

Background With the in-depth research on the tumor microenvironment, the tumor stroma is considered to play a leading role in malignant tumor behavior, and PD-L1 is also related to the tumor stroma. The tumor–stroma ratio (TSR) has been regarded as a novel prognostic factor in many cancers. Our study aims to assess the TSR and PD-L1 clinical value in hepatocellular carcinoma (HCC) patients. Methods Ninety-five patients who were diagnosed with HCC were included in our study. TSR was estimated on HCC specimen hematoxylin–eosin staining (HE) sections, and the optimal TSR cut-off value was determined by receiver operating characteristic (ROC) curves. The correlation between the TSR and clinicopathologic features was also calculated. Immunohistochemistry (IHC) staining was also carried out to analyze the PD-L1 expression level in HCCs. Results The optimal TSR cut-off value was 0.525. The median OS of the stroma-high and stroma-low groups was 27 and 36 months, respectively. The median RFS of the stroma-high and stroma-low groups was 14.5 and 27 months, respectively. In the Cox multivariate analysis, the TSR was an independent prognostic factor for HCC overall survival (OS) and recurrence-free survival (RFS) in patients who underwent liver resection. IHC staining revealed TSR-high HCC samples with high PD-L1-positive cell expression. Conclusions Our results suggest that the TSR can predict the prognosis of HCC patients who underwent liver resection. The TSR is related to PD-L1 expression and may be a therapeutic target that can dramatically improve HCC patients’ clinical outcomes.

Background The aim of this study was to investigate the predictive value of procalcitonin (PCT) on post-operative day (POD) 3 and 5 for the prognosis of gastric adenocarcinoma (GA) patients who underwent radical gastrectomy surgery in extended cohort from a prospective bi-center study. Methods Consecutive GA patients who received surgery in the Hunan Cancer Hospital were enrolled as the training cohort, and those from Wuhan Union Hospital were included as external validation cohort. The optimal cutoff concentration of PCT for overall survival (OS) in the training cohort was determined by X-tile. The independent predictive factors for OS were identified using univariate and multivariate Cox regression analyses. Furthermore, the predictive value of elevated PCT was clarified in the validation cohort and propensity score matched cohort, respectively. Results The optimal cutoff concentrations of PCT for OS were 0.67 ng/mL at POD 3 and 0.39 ng/mL at POD 5 in the training cohort (n = 906). Patients with higher PCT concentrations (≥ 0.39 ng/mL) at POD 5 had a significantly worse prognosis whether developing post-operative infections or not. Moreover, a synergistic influence was confirmed in those with elevated PCT concentration and infections. Multivariate analyses confirmed that PCT concentration ≥ 0.39 ng/mL at POD 5 was significantly associated with poorer survival in training cohort (HR: 1.422, 95% CI 1.041–1.943, P = 0.027), validation cohort (n = 297, HR: 2.136, 95% CI 1.073–4.252, P = 0.031) and matched cohort (n = 901, HR: 1.454, 95% CI 1.104–1.914, P = 0.008), separately. Conclusions PCT concentration ≥ 0.39 ng/mL at POD 5 was a reliable predictor for poorer prognosis in GA patients undergoing radical gastrectomy.

Background A high incidence of hepatocellular carcinoma (HCC), the most frequently diagnosed form of liver cancer, is observed in Africa and Asia. SYVN1 is upregulated in HCC; however, the biological roles of SYVN1 in immune evasion remain unclear. Methods RT-qPCR and western blot were employed to detect the expression levels of SYVN1 and the key molecules in HCC cells and tissues. Flow cytometry was used to determine the proportion of T cells, and an ELISA assay was used to determine the amount of IFN-γ secreted. Cell viability was monitored by CCK-8 and colony formation assays. The metastatic properties of HCC cells were detected by Transwell assays. Bioinformatics analysis, ChIP, and luciferase assays were used to study the transcriptional regulation of PD-L1. Co-IP was used to detect direct interaction between SYVN1 and FoxO1, as well as the ubiquitination of FoxO1. The in vitro findings were validated in xenograft and lung metastasis models. Results In HCC cells and tissues, SYVN1 was upregulated while FoxO1 was downregulated. SYVN1 knockdown or FoxO1 overexpression reduced PD-L1 expression, and inhibited immune evasion, cell growth, and metastasis in HCC cells. Mechanistically, FoxO1 regulated PD-L1 transcription in a β-catenin-independent or -dependent manner. Functional studies further showed that SYVN1 promoted immune evasion, cell proliferation, migration and invasion via facilitating ubiquitin-proteasome-dependent degradation of FoxO1. In vivo investigations showed that silencing of SYVN1 inhibited immune evasion and metastasis of HCC cells, possible via the FoxO1/PD-L1 axis. Conclusion SYVN1 regulates FoxO1 ubiquitination to stimulate β-catenin nuclear translocation and promotes PD-L1-mediated metastasis and immune evasion in HCC.

Background/objective To investigate the influence of pre-operative immunological and nutritional status, assessed by the prognostic nutritional index (PNI) score, on post-operative infection, and the potential additive effects of low PNI and infection on prognosis after radical resection of stage II/III gastric cancer (GC). Methods The medical records of 2352 consecutive stage II/III GC patients who underwent radical gastrectomy were retrospectively reviewed. The independent predictors for infections were identified using univariate and multivariate analyses. Cox regression analysis was used to assess any associations between PNI, infection and OS. Results A total of 160 (6.8%) cases developed infections and low PNI (< 43.9) was confirmed as an independent predictor. Both PNI < 43.9 and infections independently predicted poor OS (hazard ratio: 1.163, 95% confidence interval: 1.007–1.343; HR: 1.347, 95%CI: 1.067–1.700), and an additive effect was confirmed as patients with both low PNI and infection had worst OS. Further stratified analyses showed that complete peri-operative adjuvant chemotherapy (PAC, ≥ 6 cycles) could significantly improve OS in patients with low PNI and/or infection, which was comparable to those with PNI ≥ 43.9 and/or infection ( P = 0.160). Conclusions Infection was the most common complication after gastrectomy and PNI < 43.9 was identified as an independent predictor. Low PNI was associated with poorer OS in stage II/III GC, independent of infections, and low PNI and infections had a synergistic effect that was associated with worst OS. However, complete PAC could significantly improve OS in these patients. Thus, strategies to decrease infection and complete PAC should be further investigated.