Aim: The cardiac toxicity that occurs during administration of anti-tumor agents has attracted increasing concern. Fluoropyrimidines have been used for more than half a century, but their cardiotoxicity has not been well clarified. In this study, we aimed to assess the incidence and profile of fluoropyrimidine-associated cardiotoxicity (FAC) comprehensively based on literature data. Methods: A systematic literature search was performed using PubMed, Embase, Medline, Web of Science, and Cochrane library databases and clinical trials on studies investigating FAC. The main outcome was a pooled incidence of FAC, and the secondary outcome was specific treatment-related cardiac AEs. Random or fixed effects modeling was used for pooled meta-analyses according to the heterogeneity assessment. PROSPERO registration number: (CRD42021282155). Results: A total of 211 studies involving 63,186 patients were included, covering 31 countries or regions in the world. The pooled incidence of FAC, by meta-analytic, was 5.04% for all grades and 1.5% for grade 3 or higher. A total of 0.29% of patients died due to severe cardiotoxicities. More than 38 cardiac AEs were identified, with cardiac ischemia (2.24%) and arrhythmia (1.85%) being the most frequent. We further performed the subgroup analyses and meta-regression to explore the source of heterogeneity, and compare the cardiotoxicity among different study-level characteristics, finding that the incidence of FAC varied significantly among different publication decades, country/regions, and genders. Patients with esophagus cancer had the highest risk of FAC (10.53%), while breast cancer patients had the lowest (3.66%). The treatment attribute, regimen, and dosage were significantly related to FAC. When compared with chemotherapeutic drugs or targeted agents, such a risk was remarkably increased (χ² = 10.15, p < 0.01; χ² = 10.77, p < 0.01). The continuous 5-FU infusion for 3–5 consecutive days with a high dosage produced the highest FAC incidence (7.3%) compared with other low-dose administration patterns. Conclusions: Our study provides comprehensive global data on the incidence and profile of FAC. Different cancer types and treatment appear to have varying cardiotoxicities. Combination therapy, high cumulative dose, addition of anthracyclines, and pre-existing heart disease potentially increase the risk of FAC.

Background: Colorectal cancer (CRC) represents the third most prevalent malignancy worldwide and accounts for the second-highest cancer-related mortality rate. Accumulating evidence over the past decade has established the pivotal role of tumor-associated macrophages (TAMs) in CRC tumorigenesis and disease progression. This study employs bibliometric analysis to delineate the research landscape and emerging frontiers in CRC TAMs investigation. Methods: We systematically retrieved publications indexed in the Web of Science Core Collection from database inception through 14 April 2025, applying predefined inclusion and exclusion criteria. Using VOSviewer and CiteSpace, we conducted comprehensive visual analyses of the CRC TAMs research domain, including country contributions, institutional productivity, annual publication trends, and journal distributions. Results: Our bibliometric analysis identified 2861 publications on CRC TAMs worldwide, with a consistent upward publication trend since 2018. Geospatial analysis revealed that China and the United States are the predominant contributing nations, with Sun Yat-sen University being the most productive institution. Keyword co-occurrence mapping identified five predominant research clusters: CRC biology, TAMs characterization, patient survival outcomes, disease progression mechanisms, and metastatic processes. Four key research directions emerged: (1) single-cell RNA sequencing for TAMs heterogeneity analysis, (2) PD-1/PD-L1 checkpoint interactions with TAMs, (3) molecular mechanisms underlying macrophage polarization, and (4) chemotherapeutic modulation of TAMs functionality (particularly irinotecan). These advances provide mechanistic insights into CRC TAMs biology and may facilitate (1) the discovery of novel diagnostic biomarkers, (2) precision therapeutic strategies, and (3) personalized prognostic frameworks. Conclusion: Bibliometric analysis has highlighted the global landscape of research on CRC TAMs. Future research directions in CRC TAMs are likely to center on the integration of multi-omics, in-depth investigation of the tumor microenvironment, targeting TAMs, application of machine learning and artificial intelligence, and the development of personalized treatment strategies for CRC.

Purpose Pancreatic cancer is one of the deadliest cancers worldwide. The extracellular matrix (ECM) microenvironment affects the drug sensitivity and prognosis of pancreatic cancer patients. This study constructed an 8-genes pancreatic ECM scoring (PECMS) model, to classify the ECM features of pancreatic cancer, analyze the impact of ECM features on survival and drug sensitivity, and mine key molecules that influence ECM features in pancreatic cancer. Methods GSVA score calculation and clustering were performed in TCGA-PAAD patients. Lasso regression was used to construct the PECMS model. The association between PECMS and patient survival was analyzed and validated in the CPTAC-3 dataset of TCGA and our single-center retrospective cohort. The relationships between PECMS and features of the matrix microenvironment were analyzed. Finally, PECMS feature genes were screened and verified in pancreatic cancer specimens to select key genes associated with the ECM microenvironment. Result The survival of the PECMS-high group was significantly worse. The PECMS-high group showed higher oxidative stress levels, lower levels of antigen presentation- and MHC-I molecule-related pathways, and less immune effector cell infiltration. Data from IMvigor-210 cohort suggested that PECMS-low group patients were more sensitive to immune checkpoint blockers. The PECMS score was negatively correlated with chemotherapy drug sensitivity. The negative association of PECMS with survival and drug sensitivity was validated in our retrospective cohort. KLHL32 expression predicted lower oxidative stress level and more immune cells infiltrate in pancreatic cancer. Conclusion PECMS is an effective predictor of prognosis and drug sensitivity in pancreatic cancer patients. KLHL32 may play an important role in the construction of ECM, and the mechanism is worth further study.