Clinical & Translational Oncology最新文献

Background: Diffuse large B-cell lymphoma (DLBCL) is a clinically and molecularly heterogeneous malignancy with variable outcomes. Identification of reliable biomarkers is critical for risk assessment and targeted therapy.

Methods: We conducted a two-sample Mendelian randomization (MR) analysis to systematically evaluate the causal effects of 4907 plasma proteins on DLBCL. Transcriptomic data were integrated to screen proteins with transcriptional relevance. Bayesian co-localization and reverse MR analyses were applied to assess shared genetic variants and causal direction. Survival analyses were used to evaluate the prognostic significance of the identified biomarkers across independent cohorts.

Results: Fifty-two plasma proteins were identified as risk factors for DLBCL, of which six (GOLM1, ISOC1, MTHFD1, PPIL1, RACGAP1, and WDR5) demonstrated robust associations at both protein and transcriptional levels. No evidence of reverse causality was observed, and co-localization analyses did not support shared causal variants. Among the six biomarkers, MTHFD1, PPIL1, and WDR5 showed consistent associations with poor prognosis across cohorts.

Conclusion: This study identified novel biomarkers at both protein and transcriptional levels, offering valuable insights for risk assessment and early prognosis prediction in DLBCL.

Background: CD4⁺ T cells infiltrate the tumor microenvironment, but their role in high-grade serous ovarian cancer (HGSOC) progression remains unclear. Cell death-associated genes critically impact HGSOC advancement.

Methods: We integrated single-cell and spatial transcriptomics to analyze CD4⁺ T cell heterogeneity and identify cell death-associated genes. Key candidates were experimentally validated via qPCR and Western blotting in independent HGSOC cohorts. Furthermore, a T cell-tumor cell co-culture system was employed for functional validation of candidate gene effects on tumor behavior.

Results: To comprehensively characterize the heterogeneity of CD4⁺ T cells in HGSOC, we performed an integrated analysis including inferCNV, pseudotime trajectory, SCENIC transcription regulatory networks, and hdWGCNA. This multi-omics approach defined distinct CD4⁺ T cell subgroups and identified key regulons. Notably, a co-expression network module derived from hdWGCNA was leveraged to construct a prognostic model, which demonstrated significant predictive power for patient survival. Spatial transcriptomic analysis identified co-localized niches of IL7R⁺CD4⁺ T cells and Tregs, exhibiting highly concordant gene expression with scRNA-seq data. Orthogonal validation confirmed significant dysregulation of MAL (p < 0.001) and ANXA1 (p < 0.001) in HGSOC. Critically, in vitro co-culture experiments demonstrated that silencing MAL in T cells significantly suppressed ovarian cancer cell proliferation, migration, and invasion, highlighting its functional role in modulating the tumor microenvironment.

Conclusion: Our findings elucidate mechanisms of cell death-associated genes in CD4⁺ T cell subgroups, with experimentally grounded biomarkers offering therapeutic options for HGSOC.

Background: Cervical cancer continues to be a major worldwide health concern. Diagnostic methods are limited, and therefore, more specific, non-invasive serum biomarkers are required for greater efficacy in detecting and monitoring the disease.

Objective: This research aims to investigate the diagnostic and prognostic utility of serum Cytokeratin 5 (CK5) and p63 as biomarkers for cervical cancer.

Material and methods: A case-control study was conducted with 50 women with newly diagnosed, histologically confirmed cervical cancer and 50 age-matched healthy controls. Serum levels of CK5 and p63 were quantified using enzyme-linked immunosorbent assay (ELISA).

Results: Serum levels of both CK5 (286 ± 94 vs. 77.5 ± 28.2 ng/L, p < 0.001) and p63 (35.1 ± 10.6 vs. 7.5 ± 3.2 ng/mL, p < 0.001) were significantly elevated in cervical cancer patients compared to controls. ROC analysis revealed excellent diagnostic accuracy, with an area under the curve (AUC) of 0.96 for CK5 and 0.97 for p63 both biomarkers being statistically significantly more in advanced-stage than in early-stage of the disease on p = 0.002 and p < 0.0001, respectively, and independent predictors of advanced disease in multivariate analysis.

Conclusion: Serum CK5 and p63 had an excellent diagnostic efficiency for cervical cancer and correlated with disease progression, positioning them as promising non-invasive biomarkers for diagnosis and staging.

Background: Patients undergoing abdominoperineal or intersphincteric resection for low rectal cancer experience profound physiological and psychological stress. Conventional Enhanced Recovery After Surgery (ERAS) protocols mainly address surgical and metabolic factors but rarely target the host's psychosocial and immunometabolic recovery.

Study design: In this single-center randomized controlled trial, 240 patients with stage II-III low rectal cancer (September 2019-September 2021) were randomized (1:1) to receive either standard ERAS care or an integrated perioperative intervention combining resilience-based psychosocial support, cognitive behavioral therapy for insomnia, and Prognostic Immune Nutritional Index (PINI)-guided nutritional optimization. The primary outcomes were global quality of life (EORTC QLQ-C30) and sleep quality (Pittsburgh Sleep Quality Index). The secondary outcomes included postoperative recovery, inflammatory and nutritional indices, and 3-year disease-free and overall survival.

Results: At 12 months, the intervention group showed greater improvement in quality of life (mean difference = 12.3, 95% CI 8.6-16.0; p < 0.001) and sleep quality (-3.1, 95% CI -4.5 to -1.8; p < 0.001). Serum interleukin-6 declined more rapidly (-1.9 pg/mL vs -0.8; p < 0.001), accompanied by improved PINI (-0.7; p < 0.01) and higher fecal short-chain fatty acid levels (+ 10.6 mmol/kg; p < 0.001). Three-year disease-free survival favored the intervention (HR 0.69, 95% CI 0.51-0.93; p = 0.015). No intervention-related serious adverse events occurred.

Conclusions: Integrating psychosocial, sleep, and immunonutritional components into perioperative care enhanced functional and physiological recovery after low rectal cancer surgery. These findings support extending ERAS toward targeted modulation of host response to improve both short- and long-term outcomes.

Aim: The management of patients with advanced cancer, especially in the presence of bulky tumors, presents significant challenges for oncology practice, despite advances in conventional RT. Considering the dosimetry advantages of our dense-LRT protocol, we aimed for the first time to assess the safety and feasibility of the use of dense-LRT as exclusive radiation treatment for palliative care in locally advanced/metastatic cancer patients.

Methods: Patients diagnosed with locally advanced and/or metastatic tumors and/or inoperable patients with a high burden of disease with cancers of different etiologies were included in this prospective study of dense-Lattice Radiotherapy from October-2022, until February-2025. The dense-LRT treatment characteristics have been already published. Our study aimed to analyze the use of dense-LRT as exclusive radiation treatment, which was designed as preplanned 3 patients' cohorts in a 1:1:1 protocol. Cohort 1: 24 Gy-LRT + EBRT. Cohort 2: exclusive 24 Gy-LRT. Cohort 3: exclusive 36 Gy-LRT. The primary endpoints of the study were the feasibility and safety of the proposed treatment protocol.

Results: The dense-LRT protocol was feasible and safe with no grade 3 acute or late toxicity reported. The 3 month CR and PR response rates were 2/20 (10%) and 14/20(70%), resulting in an objective response rate of 80%. The 1-year actuarial survival was 52.1%. The Hybrid and the accelerated cohorts showed better clinical response rates. The hybrid protocol showed a slightly increase in mild adverse effects.

Conclusion: Our preliminary results could suggest that a high-dose accelerated LRT protocol (36 Gy/3fractions/5 days) is effective and a safe in the palliative treatment of bulky tumors. Further study is needed to define its role in palliative cancer care.

Aims: Despite the established use of both liposomal irinotecan and conventional irinotecan, a comparative analysis of their safety profiles is lacking. This study leverages the FDA Adverse Event Reporting System (FAERS) database to fill this gap by comparing their adverse events (AEs) to inform clinical practice.

Methods: AEs were categorized by System Organ Class (SOC) and described using Preferred Terms (PTs) from the Medical Dictionary for Regulatory Activities (MedDRA, v26.1). The signals for liposomal irinotecan and irinotecan were quantified through disproportionality analysis, employing multiple algorithms: the reporting odds ratio (ROR), proportional reporting ratio (PRR), multi-item gamma poisson shrinker (MGPS), and Bayesian confidence propagation neural network (BCPNN).

Results: A total of 934 and 10,362 AE reports were retrieved for liposomal irinotecan and irinotecan, respectively, with each drug involving 25 and 27 System Organ Class (SOC) categories. At the SOC level, both drugs have significant SOC-level signals value for "Gastrointestinal Disorders", "Neoplasms Benign, Malignant And Unspecified (Incl Cysts And Polyps)", "Blood And Lymphatic System Disorders", "Metabolism And Nutrition Disorders", "Hepatobiliary Disorders", and "Congenital, Familial And Genetic Disorders". For liposomal irinotecan, 61 effective PT-level signals were detected, dominated by gastrointestinal disorders (diarrhoea). For irinotecan, 431 effective PT-level signals were detected, dominated by gastrointestinal disorders (diarrhoea) and blood and lymphatic system disorders (neutropenia). Comparative analysis revealed distinct safety profiles between the two drugs. Irinotecan demonstrated a stronger association with hematological and gastrointestinal events, including neutropenia, febrile neutropenia, and diarrhea, as well as with decreased appetite. For patients treated with liposomal irinotecan and irinotecan, the majority of AEs manifested within 30 days after the initiation of therapy.

Conclusion: As the first FAERS-based study comparing liposomal irinotecan and irinotecan, this analysis provides crucial evidence for clinical decision-making. While the detected signals indicate statistical associations, further clinical studies are warranted to establish causality and strengthen drug safety evaluation.

Nasopharyngeal carcinoma is distinct from other cancers of the head and neck in biology, epidemiology, histology, natural history, and response to treatment. Radiotherapy is the cornerstone of locoregional treatment of non-disseminated disease and, in combination with chemotherapy, improves survival rates. In the case of metastatic disease stages, treatment requires platinum/gemcitabine-based chemotherapy, and patients may achieve a long survival time. In these guidelines (updated in 2025), we summarize current evidence and available therapies for the medical management of advanced nasopharyngeal carcinoma.

Anticancer therapies frequently compromise skeletal health and increase fracture risk. This narrative review synthesizes information and provides guidance on assessment, prevention, and management of therapy-related bone loss in adults with cancer. Major contributors to bone loss in this population include aromatase inhibitors, androgen deprivation therapy, systemic glucocorticoids, chemotherapy, and selected targeted or immune agents. Recommended assessments include clinical evaluation, laboratory tests (calcium, vitamin D, and renal function), and bone mineral density by dual-energy X-ray absorptiometry with vertebral fracture assessment and, when acute vertebral fracture is suspected, magnetic resonance imaging. Prevention measures include exercise, adequate calcium and vitamin D intake, and fall-reduction strategies. Pharmacological treatment options include bisphosphonates and denosumab. Selection of treatment should consider skeletal efficacy and potential oncological benefits, while ongoing care includes repeat bone density testing at 12-24 months and vigilance for osteonecrosis of the jaw and atypical femoral fractures.

Purpose: Neutrophil-to-lymphocyte ratio (NLR) is a widely studied variable to investigate the systemic inflammation-related prognostic effect, and in some clinical setting has been able to predict the activity of immunotherapy. Many studies confirmed a negative relationship of pre-treatment high NLR and the outcome of patients with esophageal squamous cell cancer (ESCC), but poor data are available for patients with unresectable or metastatic ESCC (mESCC). The study aims to perform a trial-level analysis of the relationship of NLR with overall survival (OS) among mESCC patients receiving an upfront systemic treatment.

Methods: A systematic literature review of studies enrolling mESCC patients receiving an upfront chemotherapy-based regimen and reporting the hazard ratio and confidence intervals of the relationship of NLR with OS were carried out. A meta-analysis was performed, calculating a global effect size, and another one evaluated only immunotherapy-based studies. Finally, based on the resulting between-study heterogeneity, a meta-regression evaluated the possible inference of the more frequently reported baseline variables on the relationship.

Results: Twenty-three articles, including 24 study cohorts, were selected, including 3590 patients. The meta-analysis calculated a significant effect size for the relationship of NLR with OS (HR 2.01, CI 1.64-2.45), that was maintained among the 16 immunotherapy-based studies (HR 2.12, CI 1.58-2.84). The significant heterogeneity between studies (Q = 126.24, p-value < 0.0001; I² = 81.8%) allowed to perform the planned meta-regressions. However, none of the 10 baseline variables was able to influence significantly the relationship of NLR wih OS.

Conclusions: Baseline NLR is a reliable prognostic factor of mESCC patients receiving upfront chemotherapy-based regimens, with a lightly more pronounced effect size when the regimen included.