BMC Cancer最新文献

Background: Tumor-associated macrophages (TAMs) comprise heterogeneous subtypes with context-dependent functions in tumor immunity. Although macrophage senescence influences diverse diseases, its role in neuroblastoma (NB) progression remains undefined.

Methods: Single-cell RNA sequencing (scRNA-seq) data from NB samples (GEO: GSE147766) were analyzed to identify TAM subtypes. Senescence-associated signatures were characterized via pseudotime trajectory, cell-cell communication, and functional assays. A prognostic model was developed using Cox/LASSO regression and validated in independent cohorts (TARGET-NBL, E-MTAB-8248). Drug sensitivity and immune microenvironment differences were compared between risk groups. In vitro validation assessed EIF5's role in TAM senescence and NB progression.

Results: We identified a senescent TAM subset (C0) exhibits a hybrid M1/M2 state with a dominance of M2-like features. Pseudotime analysis revealed differentiation from non-senescent TAMs (C1), accompanied by upregulated LILRB1, LILRB2, IL10, and CXCL8. A 7-gene prognostic signature (AMD1, ARL4A, BRD2, DDX3X, EIF5, SLC43A2, ZEB2) stratified patients into risk groups with distinct survival (P < 0.001). High-risk patients displayed impaired anti-tumor immunity (reduced CD8⁺ T cells, elevated TIDE scores) and differential drug sensitivity. EIF5 knockdown suppressed senescence markers (p21/p16) in macrophages and inhibited NB cell proliferation/migration.

Conclusions: Senescent TAMs influence NB immunosuppression and progression. EIF5 is a key regulator of TAM senescence and a potential therapeutic target. Our risk model may guide clinical stratification and targeted interventions.

Background: Liver hepatocellular carcinoma (LIHC) is one of the most common and aggressive malignancies worldwide, with high mortality rates. PLOD family genes (PLOD1, PLOD2, and PLOD3) play a pivotal role in extracellular matrix (ECM) remodeling, which contributes to cancer progression and metastasis. This study explores the diagnostic, prognostic, and therapeutic potential of PLOD1, PLOD2, and PLOD3 in LIHC.

Materials and methods: Seven LIHC cell lines and five normal liver tissue cell lines were cultured. RT-qPCR was used to assess the expression of PLOD genes. The GSCA and TCGA databases were used for gene expression, pathway analysis, survival, and enrichment analysis. Promoter methylation was analyzed via GSCA and OncoDB, and mutational and CNV analyses were conducted using the cBioPortal database. The KM plotter tool assessed the prognostic significance of PLOD genes, while miRNA-mRNA network analysis was performed using the mirNET and UALCAN databases. Functional assays, including siRNA-mediated knockdown, Western blotting, cell proliferation, colony formation, and wound healing assays, were used to assess the biological roles of PLOD2 and PLOD3 in LIHC.

Results: The expression of PLOD1, PLOD2, and PLOD3 was significantly (p-value < 0.05) higher in LIHC cell lines compared to normal controls. Validation in the TCGA cohort confirmed upregulation of PLOD genes in LIHC tumors, with PLOD2 and PLOD3 showing progressively higher expression across pathological stages. PLOD genes were associated with the activation of oncogenic pathways such as epithelial-to-mesenchymal transition (EMT) and poor survival outcomes. Promoter methylation analysis revealed lower methylation in tumor samples. Kaplan-Meier survival analysis indicated that higher PLOD expression correlated with poorer overall survival (OS) and relapse-free survival (RFS) in LIHC patients. The miRNA-mRNA network identified three miRNAs (hsa-miR-503-5p, hsa-miR-195-5p, and hsa-miR-193a-3p) regulating PLOD genes, with aberrant miRNA expression linked to poor prognosis. PLOD2/3 knockdown in HepG2 and Hep3B cells significantly reduced cell proliferation, colony formation, and migration, highlighting their critical roles in tumor progression.

Conclusion: Our study demonstrates that PLOD1, PLOD2, and PLOD3 are significantly upregulated in LIHC and correlate with poor prognosis. The PLOD genes may serve as valuable biomarkers for diagnosis and prognosis in LIHC. Moreover, targeting PLOD genes could provide new therapeutic strategies to hinder tumor progression and metastasis in liver cancer.

Background: Oropharyngeal squamous cell carcinoma (OPSCC) is increasing worldwide, with a well-established link to human papillomavirus (HPV). However, evidence on how lifestyle risk factors-particularly smoking, alcohol consumption, and betel-quid chewing-modify the prognostic impact of HPV-associated disease remains limited, especially in regions with high exposure burden such as Taiwan. Understanding the interplay between viral and lifestyle determinants is essential for accurate prognostication and treatment planning.

Methods: We conducted a retrospective cohort study of 5,671 OPSCC patients using data from the Taiwan Cancer Registry between 2018 and 2021. p16 status was used as a surrogate marker for HPV infection. Overall survival and cancer-specific survival were compared across p16 status, age, sex, tumor location, cancer stage, lifestyle risk factors and treatment pattern using Kaplan-Meier method and multiple Cox models. Treatment-stratified analyses were additionally performed to evaluate whether lifestyle risk factors modified prognosis within p16-positive disease.

Results: Overall, 23.2% of OPSCC cases were p16-positive, with substantially higher p16 positivity among females (52.5%) and in tonsillar subsites. p16-positive patients had significantly better 5-year overall survival (69.0%; 95% CI, 66.0%-71.8%) than p16-negative patients (37.9%; 36.1%-39.6%). However, among p16-positive individuals, the presence of multiple lifestyle risk factors markedly attenuated the survival advantage, reducing 5-year overall survival from 78.6% (74.0%-82.5%) in those without lifestyle exposures to 57.6% (52.6%-62.4%) in those with smoking plus other risks. These gradients persisted after multivariable adjustment and across treatment modalities. In contrast, lifestyle risk factors were not independently associated with survival in p16-negative OPSCC, where prognosis was primarily driven by tumor stage, subsite, and treatment.

Conclusions: This nationwide study provides novel evidence that the prognostic benefit associated with p16 positivity is substantially attenuated by multiple lifestyle risk factors. These findings highlight the importance of integrating viral and behavioral determinants into prognostic assessment and treatment planning. They also underscore the need to pair HPV-associated prevention strategies with efforts to reduce tobacco, alcohol, and betel-quid use in regions with high burdens of these exposures.

Background: The prognostic significance of high mobility group box 1 (HMGB1) expression in the non-small cell lung cancer (NSCLC) population remains controversial. This study endeavors to systematically evaluate the relation of HMGB1 expression levels to NSCLC prognosis via a comprehensive meta-analysis.

Methods: Embase, the Cochrane Library, Web of Science, as well as PubMed were retrieved for eligible studies until September 18, 2025. Two reviewers independently extracted relevant data and appraised the study quality. The study quality was examined via the Newcastle-Ottawa Scale (NOS). Hazard Ratio (HR) with corresponding confidence intervals (CIs) for survival outcomes were calculated and summarized respectively. Subgroup analysis, regression analysis, sensitivity analysis and publication bias were conducted to investigate the findings further.

Results: 11 studies on 4,527 NSCLC patients were encompassed. All eligible studies had high methodological quality. The pooled HR of OS was 1.08 (95% CI: 0.91-1.29, P = 0.356), suggesting no significant association of HMGB1 expression levels with NSCLC prognosis. Subgroup analysis of studies with sample sizes < 100 revealed a significant relation of high HMGB1 expression to poorer OS (HR: 1.51, 95% CI: 1.22-1.87). Conversely, when HMGB1 expression level was detected before chemotherapy, high HMGB1 expression was linked to improved OS (HR: 0.96, 95% CI: 0.93-0.99).

Conclusion: This meta-analysis demonstrated that HMGB1 expression was not significantly associated with OS in the overall NSCLC population, but may have context-dependent prognostic value warranting further investigation.

Background: Tumor deposits (TD) have been identified as adverse prognostic indicators in gastric cancer (GC); however, their incorporation into the TNM staging system remains controversial. This study aimed to determine the most effective approach for integrating TD into the TNM staging system to improve prognostic accuracy.

Methods: A retrospective analysis was performed on clinicopathological and follow-up data from patients who underwent radical surgery for gastric cancer (GC) at Yijishan Hospital, affiliated with Wannan Medical College, between January 2012 and December 2021. Patients were classified into TD-negative and TD-positive groups according to the presence or absence of TD in postoperative pathological reports.

Results: A total of 4,972 patients were analyzed, of whom 575 (11.56%) had TD. These patients were matched in a 1:1 ratio with 523 TD-negative patients. Several clinicopathological factors, including tumor size, T stage, N stage, neural invasion, and vascular invasion, were significantly associated with the presence of TD. Survival analysis revealed that patients with TD had significantly lower 5-year overall survival (OS) rates than those without TD across all TNM stage subgroups (I-II, IIIa, IIIb, and IIIc) (P < 0.05). The 5-year OS rates of patients with TD in stages I-II, IIIa, IIIb, and IIIc were comparable to those of TD-negative patients in stages IIIa, IIIc, IIIc, and IV, respectively (P > 0.05). The proposed staging system incorporating TD demonstrated the highest χ² value (181.658), the highest C-index (0.634), and the lowest - 2 log-likelihood (8427.456), indicating improved prognostic stratification.

Conclusion: TD represent independent prognostic factors in GC, distinct from the T, N, and M categories, and should be incorporated into the TNM staging system.