Cancer Medicine最新文献

Background: Hepatocellular carcinoma (HCC) is a highly aggressive malignancy characterized by metabolic reprogramming that supports tumour growth and survival. This study identifies farnesyl diphosphate synthase (FDPs), a key enzyme in the mevalonate pathway, as a critical regulator of HCC proliferation and apoptosis.

Methods: We applied bioinformatics analysis through TCGA and GSE database to identify the expression of FDPs within HCC patients. Then, mechanistic studies were conducted including Western blots, apoptosis assay, RT-qPCR, rescue assay, RNA-sequencing, in vivo study to prove the role of FDPs in regulating HCC progression.

Results: FDPs was found to be significantly upregulated in HCC tissues, and its down-regulation promotes tumour cell apoptosis while inhibiting tumour cell proliferation in vitro and in vivo. Mechanistically, we identified FDPs regulate glucose-6-phosphate dehydrogenase (G6PD) by RNA sequencing, bioinformatics prediction, and rescue experiments, indicating its involvement in glycolysis regulation in tumour cells. The identification of this FDPs-G6PD axis suggests a novel metabolic pathway contributing to HCC development.

Conclusion: In summary, this study highlights FDPs play an essential oncogenic role in HCC, linking it to metabolic reprogramming and tumour survival. These findings establish FDPs as a promising therapeutic target, offering a foundation for further exploration of its regulatory mechanisms and potential clinical applications.

Objectives: Progression of hepatocellular carcinoma (HCC) and cardiovascular thrombosis (CVT) has a bidirectional causal relationship. CVT complications will increase in patients with HCC due to etiology shift from viral hepatitis to metabolic dysfunction-related steatohepatitis.

Aim: This study aimed to evaluate the clinical impact of CVT, focusing on patients with HCC treated after transarterial chemoembolization.

Methods: A retrospective cohort study enrolled 402 patients including 79 patients with CVT in a single university hospital. Cox proportional hazard model analysis was performed to identify independent prognostic factors. After adjusting for baseline characteristics by propensity score matching, the survival impact of the CVT complication was evaluated using the Kaplan-Meier curve.

Results: A multivariate analysis determined that CVT complication was an independent risk factor for overall deaths in patients with HCC (HR = 1.751, IQR 1.203-2.548, p < 0.05). Propensity score matching generated a pair of 54-patient cohorts. The median survival time of patients with CVT (1106 days) shortened to half compared to those without CVT (2707 days, HR = 2.298, IQR: 1.399-4.169, p = 0.0020). While recurrence-free survival was not significantly different (p > 0.05), post-recurrence survival was shorter in patients with CVT (2150 days vs. 1008 days, HR = 1.945, IQR: 1.150-3.740, p = 0.0188).

Conclusions: Assuming that the expected life expectancy is only half that of uncomplicated cases of CVT, CVT might be a major prognostic factor in patients with HCC, following tumor burden and functional hepatic reserve.

Background: Platinum-based two-agent chemotherapy combined with immunotherapy is now the first-line standard of care for extensive-stage small cell lung cancer (ES-SCLC). Further studies are needed to determine whether continuing immunotherapy (IO) can provide benefit in patients whose disease has progressed after first-line treatment. Therefore, we conducted a retrospective study to evaluate the efficacy of continuing IO in patients.

Methods: The study retrospectively collected clinical data of ES-SCLC patients as progressive disease (PD) after receiving first-line treatment with PD-1/PD-L1 inhibitors. According to whether to continue immunotherapy or not, patients were divided into the continuing IO group and the control group. The differences in progression-free survival (PFS2, defined as time from progression on first-line treatment to progression on second-line treatment) and overall survival (OS) between the two groups were compared.

Result: As a result, a total of 489 patients from three cancer centers were enrolled in this study, of which 298 patients were included in the continuing IO group and 191 patients were included in the control group. By analysis, it was found that continuing IO could prolong OS (median: 18.82 months vs. 16.43 months, p = 0.008) and PFS2 (median: 4.13 months vs. 3.77 months, p = 0.04) compared to the control group. In subgroup analyses, continuing immunotherapy led to prolonged survival in patients with an initial efficacy evaluation of the complete response (CR) or partial response (PR). And there was also no difference in survival between the PD-L1 inhibitor group and the PD-1 inhibitor group in the comparison of different ICIs types.

Conclusions: Continuation of immunotherapy after standard first-line immunotherapy plus chemotherapy can improve survival in patients with ES-SCLC.

Aim: This study aimed to clarify the clinical characteristics of patients with advanced hepatocellular carcinoma (HCC) who transitioned to subsequent therapies following systemic therapy (ST).

Methods: In total, 136 patients with unresectable HCC (26 hepatitis B, 47 hepatitis C and 63 others) receiving first-line ST, including 31 patients treated with immune checkpoint inhibitors (ICIs), were enrolled. Clinical characteristics and adverse events observed during treatment, as well as overall survival (OS), progression-free survival and post progression survival (PPS), were compared between patients who transitioned to subsequent therapies (2nd therapy group, n = 66) and those who did not (non-2nd therapy group, n = 70).

Results: Significant differences between the two groups were observed in OS (29.3 vs. 10.7 months, p < 0.001), PPS (11.3 vs. 2.9 months, p < 0.001), ALBI score (-2.48 vs. -2.34, p = 0.018), treatment with/without ICIs (24/42 vs. 7/63, p < 0.001), TNM stage (II/III/IVA/IVB; 15/26/7/18 vs. 3/27/10/30, p = 0.008) and the adverse events of appetite loss (p = 0.009) and proteinuria (p = 0.006). A favourable ALBI score (p = 0.005), treatment with ICIs (p = 0.002) and earlier TNM stage (p = 0.027) identified by logistic regression analysis and TNM stage II in men and prothrombin time ≥ 105% in women by classification tree analysis were found to be associated with a higher likelihood of transitioning to subsequent therapies.

Conclusions: Initiating systemic therapy, including ICIs, before clinical stage progression and preserving the hepatic reserve is crucial for ensuring a smooth transition to subsequent therapies. REGISTRY AND THE REGISTRATION NO.

Of the study/trial: N/A.

Objective: There is a lack of studies investigating Cancer therapy-induced thrombocytopenia (CTIT) and the risk factors predicting CTIT-related hemorrhage in the emergency oncology patient population. This study aimed to present Chinese data on CTIT and organ bleeding in patients undergoing emergency oncology.

Methods: This retrospective study was conducted in the Oncology Emergency Department. We evaluated the clinical features and outcomes of CTIT and associated organ hemorrhage.

Results: A retrospective analysis collected data from 8590 cases of malignant tumor emergency visits. Among these, 1164 cases (13.5%) of CTIT met the inclusion criteria, with a median patient age of 61 years. 61 (5.24%) of the 1164 CTIT cases were associated with overt organ hemorrhage. Independent risk factors predicting CTIT deterioration included Eastern Cooperative Oncology Group (ECOG) score of 2-4 (odds ratio [OR] = 4.883), stage IV (OR = 2.275), organ bleeding (OR = 3.029), anemia (OR = 3.243), and fever (OR = 5.360), all with p < 0.05. Among the 61 cases with bleeding, 41% (25/61) involved lung cancer. The bleeding group had a significantly higher proportion of patients with fever (11.5% vs. 2.9%), pleural effusion (25.0% vs. 9.8%), and malnutrition requiring parenteral nutritional support (9.8% vs. 2.8%) compared to the non-bleeding group (p < 0.05). Fever (OR = 4.886, p = 0.003) and pleural effusion (OR = 4.812, p = 0.007) were identified as independent risk factors for CTIT-related bleeding.

Conclusion: Malignancies associated with reduced platelet counts and additional risk factors require heightened clinical vigilance for hemorrhage development.

Background: Anti-programmed death 1 (PD-1) and anti-programmed death ligand 1 (PD-L1) immune checkpoint inhibitors (ICIs) have changed the treatment landscape of many advanced malignancies. However, immune-related adverse events (irAEs) bring great challenges to clinical benefits. The prediction of irAEs is urgently demanded for early detection and intervention.

Methods: Patients in our center who received anti-PD-(L)1 immunotherapy between January 2019 and May 2023 were collected. Logistic least absolute shrinkage and selection operator (LASSO) regression analysis with 10-fold cross-validation was performed to identify the most relevant variables associated with irAEs. Multivariate logistic regression analysis was used to build a prediction model by introducing features selected in LASSO regression analysis.

Results: Overall, 680 eligible patients were included, of whom 330 patients were included in the irAEs group. In the irAEs group, 455 different irAEs were reported, of which 52 events were grade 3 or higher in severity. Endocrinal toxicities (174/680, 25.59%) were the most commonly reported irAEs. Through LASSO and logistic regression analysis, we developed a risk assessment model to predict the risk of irAEs based on basophil percentage (BASO%), hemoglobin (Hb), absolute lymphocyte count (ALC), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), blood urea nitrogen level (BUN), the Charlson comorbidity index (CCI) score, Eastern Cooperative Oncology Group Performance Status (ECOG PS), and hepatitis B/hepatitis B surface antigen carriers. The model had a C-index of 0.727, with good discrimination and calibration capabilities.

Conclusion: The prediction model developed in our study can screen and monitor patients with high risk of developing irAEs. It may improve prognosis for pan-cancer patients receiving anti-PD-(L)1 immunotherapy.

Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality with limited therapies. Reprogrammed lipid metabolism, driven by upregulated de novo lipogenesis, is a key tumorigenic mechanism. The enzyme ACSL3 is strongly correlated with poor HCC prognosis, positioning it as a potential therapeutic target.

Material and methods: ACSL3 expression was assessed in vivo and ex vivo using comparative analysis. Bioinformatic investigations, including gene set enrichment analysis (GSEA) and KEGG pathway analysis, were employed to identify signaling pathways and biological processes associated with ACSL3 overexpression.

Results: ACSL3 expression was consistently elevated in HCC models. Enrichment analyses revealed that high ACSL3 levels are associated with activation of the STAT3 signaling pathway and upregulation of key lipogenic enzymes, suggesting a feedforward oncogenic loop. Predictive data also indicate a correlation between ACSL3 expression and the immune checkpoint regulator PD-L1.

Conclusion: These findings underscore ACSL3 as a significant biomarker and candidate therapeutic target in HCC. Its role bridges dysregulated lipid metabolism with oncogenic signaling and immune evasion, warranting further investigation into ACSL3-targeted strategies.