American journal of cancer research最新文献

Objective: To evaluate the diagnostic value of combined detection of serum carcinoembryonic antigen (CEA), thyroglobulin (Tg), calcitonin (CT), and thyroid-stimulating hormone (TSH) using a chemiluminescence assay in thyroid carcinoma (TC).

Methods: A total of 320 inpatients with TC - including 261 with papillary TC, 37 with follicular TC, 19 with medullary TC, and 3 with undifferentiated TC - were enrolled as the TC group. Meanwhile, 120 healthy individuals undergoing routine examinations and 120 patients with benign thyroid diseases were included as the control group. Serum levels of CEA, Tg, CT, and TSH were compared between groups and among different pathological types of TC. ROC curves were constructed to assess the diagnostic performance of each biomarker alone and in combination.

Results: The combined detection of the four biomarkers yielded a sensitivity of 75.63%, accuracy of 75.54%, and negative predictive value of 69.88%, all higher than those of any single biomarker. ROC analysis showed that the AUC for the combined test of four markers and for the combination of CEA and Tg were 0.840 and 0.768, respectively, both exceeding those of individual tests. The four-marker combination demonstrated the highest diagnostic value.

Conclusion: Combined measurement of serum CEA, Tg, CT, and TSH significantly enhances the diagnostic efficacy for TC, reducing both misdiagnosis and missed diagnosis rates, and provides a reliable basis for early clinical detection and intervention.

Background: Accurate preoperative staging of endometrioma (EC) is essential for optimal treatment planning. This study aims to evaluate the diagnostic performance of intravenous contrast-enhanced ultrasound (IV-CEUS) as a potential modality for EC staging.

Methods: This retrospective study involved 71 patients with histologically confirmed EC who were admitted to Tianjin Central Hospital of Gynecology Obstetrics between January 2021 and August 2024. All patients had undergone both IV-CEUS and magnetic resonance imaging (MRI) within 14 days before surgery. IV-CEUS was performed using high-end Doppler ultrasound systems with SonoVue^® contrast, while MRI was conducted on a 1.5 T scanner employing T2 weighted, diffusion-weighted, and dynamic contrast-enhanced sequences. Deep myometrial invasion (DMI; ≥ 50%) and cervical stromal invasion (CSI) were assessed, with final histopathological findings serving as the reference standard. Diagnostic performance was evaluated using sensitivity, specificity, predictive values, accuracy, Kappa coefficients, and receiver operating characteristic (ROC) curves.

Results: For DMI diagnosis, IV-CEUS demonstrated a sensitivity of 74.2%, specificity of 92.5%, PPV of 88.5%, NPV of 82.2%, and accuracy of 84.5% (κ = 0.68). MRI showed a sensitivity of 90.3%, specificity of 85.0%, and accuracy of 87.3% (κ = 0.75). For CSI diagnosis, IV-CEUS had a sensitivity of 69.2%, specificity of 93.1%, an accuracy of 88.7% (κ = 0.62), while MRI had a sensitivity of 76.9%, specificity of 87.9%, and accuracy of 85.9% (κ = 0.60). The areas under the curves (AUCs) were 0.704 (95% CI: 0.584-0.824) for IV-CEUS and 0.718 (95% CI: 0.602-0.834) for MRI in diagnosing DMI; and those were 0.852 (95% CI: 0.743-0.961) for IV-CEUS and 0.838 (95% CI: 0.721-0.955) for MRI in diagnosing CSI.

Conclusion: IV-CEUS demonstrates comparable diagnostic performance to MRI in assessing DMI and CSI in EC patients. It may serve as a viable alternative when MRI is contraindicated or unavailable.

Lung cancer, one of the most prevalent and lethal malignancies in clinical practice, is characterized by high incidence and mortality, and poor prognosis. Cuproptosis, a recently identified form of cell death, has emerged as a focal point in tumor diagnosis and therapy. To elucidate the role of cuproptosis in lung cancer progression and identify potential therapeutic agents, we employed bioinformatics approaches to analyze public databases, aiming to uncover key copper-related genes and pathways associated with lung cancer. Using the GSE21933 dataset, we identified 2,892 differentially expressed genes (DEGs) in lung cancer, comprising 1,369 upregulated and 1,523 downregulated genes. By intersecting these DEGs with cuproptosis-related genes, we identified three hub genes (CDK1, FOXM1, and PRC1) using VM, random forest, and MCODE algorithms. Targeted drug prediction using the DsigDB module of the Enrichr website revealed LUCANTHONE as the top candidate. Western blot, RT-qPCR, and immunofluorescence analyses confirmed that CDK1, FOXM1, and PRC1 were highly expressed at both protein and mRNA levels in lung cancer tissues and cells. Treatment of A549 lung cancer cells with LUCANTHONE resulted in decreased expression of CDK1, FOXM1, and PRC1, reduced cell proliferation and invasiveness, and increased apoptosis. Our findings demonstrate that CDK1, FOXM1, and PRC1 are critical components of the cuproptosis pathway in lung cancer, and LUCANTHONE may serve as a promising therapeutic agent for inhibiting their expression and suppressing lung cancer progression.

Pancreatic cancer is a highly aggressive malignancy associated with poor prognosis and early metastasis. However, the molecular mechanisms underlying its invasive behavior remain incompletely understood. Here, we identified WD repeat domain 3 (WDR3) as a key driver of pancreatic cancer cell invasion. WDR3 expression is significantly elevated in liver metastatic lesions and is correlated with disease progression. Functional assays revealed that WDR3 promotes cell migration and invasion by upregulating transforming growth factor-α (TGF-α). Mechanistically, WDR3 interacts with the m6A reader YTH domain-containing protein 1 (YTHDC1) and facilitates its K63-linked ubiquitination, resulting in increased cytoplasmic localization of YTHDC1. This modification enhances the stability of TGF-α mRNA, thereby promoting its expression. Knockdown of either WDR3 or YTHDC1 impairs TGF-α expression and suppresses cancer cell invasiveness, whereas YTHDC1 overexpression restores the metastatic phenotype in WDR3-deficient cells. Our findings reveal a novel WDR3-YTHDC1-TGF-α axis that drives pancreatic cancer progression and suggest that targeting WDR3 may be a promising therapeutic strategy.

This prospective observational study investigated the efficacy of pembrolizumab administered as first-line therapy and the survival outcomes of continuing or combining it with other agents after disease progression in patients with stage IV non-small cell lung cancer (NSCLC). A total of 63 patients who experienced disease progression following pembrolizumab-based first-line treatment between February 2019 and July 2024 were prospectively enrolled. Patients were randomized into two cohorts based on treatment strategy: a treated beyond progression (TBP) group (n = 39) to receive continued pembrolizumab monotherapy or pembrolizumab-based combination regimens after disease progression, and a non-TBP (NTBP) group (n = 24), which discontinued pembrolizumab upon progression. The primary endpoint was overall survival (OS), and secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). The median PFS during first-line therapy (mPFS1) was 6.97 months. In the TBP group, the median PFS from first-line initiation to progression after second-line therapy (mPFS2) was 17.6 months, with an ORR of 20.5% and a DCR of 74.4%. OS in the TBP group was significantly longer than that in NTBP group (29.4 vs. 12.4 months, P < 0.001). Multivariate Cox regression analysis identified continued pembrolizumab use and favorable ECOG performance status as independent predictors of prolonged OS. These findings suggest that continued pembrolizumab use or combination therapy after disease progression significantly enhances survival benefits in advanced NSCLC, underscoring the importance of individualized treatment strategies based on clinical characteristics and treatment response.

Objective: To develop and validate a predictive model based on computed tomography (CT) imaging features for predicting prognosis in primary liver cancer patients undergoing transcatheter arterial chemoembolization (TACE) combined with targeted immunotherapy.

Methods: This retrospective cohort study included 200 patients (training cohort) treated from May 2021 to May 2024. Patients were classified into Good Prognosis (complete response/partial response/stable disease [CR/PR/SD], n=97) or Poor Prognosis (PD/death, n=103) groups based on Response Evaluation Criteria in Solid Tumors (RECIST) criteria at post-treatment one year. Clinical data, biochemical markers, and multiphase CT features (Non-contrast, Arterial, Venous, Delayed) were analyzed. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for patients' prognosis. A predictive model was built and validated internally and externally (n=85).

Results: Child-Pugh class, C-reactive protein (CRP), alpha-fetoprotein (AFP), aspartate aminotransferase (AST), and CT density characteristics across phases (non-contrast phase [NP], arterial phase [AP], venous phase [VP], delayed phase [DP], All-Phases [All-P]) significantly differed between groups (P < 0.05). Multivariate analysis identified Child-Pugh class (odds ratio [OR]=0.345, P=0.030), AFP (OR=0.989, P=0.022), and Non-contrast Phase density (OR=4.378, P=0.032) as independent predictors. The model showed good prediction ability, with an area under the curve (AUC) of 0.811 in the training cohort and 0.931 in the test cohort, demonstrating robust predictive performance.

Conclusion: The predictive model integrating CT imaging features, especially tumor density in non-contrast phase, alongside Child-Pugh class and AFP, demonstrate robust predictive performance for risk stratification and personalized treatment planning.

Glioblastoma (GBM) is a highly malignant primary brain tumor, accounting for 50% of gliomas, with limited therapeutic targets and an immunosuppressive tumor microenvironment (TME). γδT cells, a subset of T cells with innate and adaptive immune functions, exhibit potent antitumor activity. Compared with γδT cells, Chimeric Antigen Receptor γδT (CAR-γδT) cells show enhanced tumor-targeting ability and superior efficacy in solid tumors, representing a promising strategy for GBM. Programmed Death Ligand 1 (PDL1), highly expressed on GBM cells and a key mediator of immunosuppressive TME, is an attractive target for GBM therapy. Here, we constructed three PDL1-targeted CAR-γδT cells using nanobodies (VHHs) with good binding ability and certain blocking functions. In vitro, these cells exhibited significant cytotoxicity against U87-MG and U138-MG cells, accompanied by the release of cytotoxic cytokines. Under repeated PDL1 antigen stimulation, all three PDL1-CAR-γδT cells continuously resisted tumor antigen while maintaining high activation and minimal exhaustion. In a cell-derived xenograft (CDX) mouse model, PDL1-CAR-γδT cells effectively suppressed GBM growth. These results suggest that PDL1-CAR-γδT cells represent a novel and promising therapeutic strategy for GBM.

[This corrects the article on p. 2406 in vol. 7, PMID: 29312796.].

Objectives: This study aimed to evaluate the clinical response of intensity-modulated radiation therapy (IMRT) in advanced sinonasal cancer (SNC), and to investigate the clinicopathological factors influencing treatment outcomes.

Methods: A retrospective analysis was conducted on data from 110 patients with advanced SNC admitted between 2016 and 2020. After balancing baseline characteristics through propensity score matching, 96 patients were included in the analysis and divided into an observation group (OG, n=48) and a control group (CG, n=48). OG received IMRT combined with docetaxel and cisplatin chemotherapy, while CG received IMRT alone. Clinical data, molecular biomarker expression levels, and remedy outcomes were compared. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify factors influencing patients' overall survival (OS).

Results: No significant differences existed in baseline characteristics between groups (all P>0.05). OG demonstrated significantly superior outcomes versus CG in terms of overall clinical response rate, 3-year OS, progression-free survival (PFS), and local recurrence-free survival (LRFS) (all P<0.05). Multivariate analysis identified the following independent risk factors: radiotherapy alone (affecting OS, PFS, LRFS); advanced age and poor differentiation (affecting OS); positive expression of epidermal growth factor receptor and vascular endothelial growth factor (affecting OS and PFS); cervical lymph node metastasis (affecting PFS and LRFS); and positive P53 expression (affecting OS and LRFS) (all P<0.05).

Conclusion: IMRT combined with docetaxel and cisplatin chemotherapy significantly improves the prognosis of advanced SNC. Treatment modality, patient age, tumor differentiation, lymph node status, and molecular markers are all independent prognostic factors, indicating the potential for individualized treatment strategies under comprehensive assessment.

Colorectal cancer (CRC) is influenced by both enteroviruses and bacteria, yet current microbial typing schemes rely primarily on bacterial data. To construct a more comprehensive microbial typing scheme for CRC, this study integrated enteroviral and bacterial profiling data from fecal samples of 414 healthy controls (NCs), 151 advanced adenoma (AAs) patients, and 255 CRC patients using Illumina sequencing. Metabolites and trace elements were analyzed via liquid chromatography and ICP-MS, respectively. Microbial subtyping was performed with ConsensusClusterPlus based on combined viral and bacterial sequencing data, leading to the identification of two initial viral subtypes (V1, n=309; V2, n=511). The V2 group was further split into two bacterial subtypes (V2B1, V2B2), yielding three distinct microbial subtypes. Disease ratios (CRCs&AAs/NCs) were 1.06 (V1), 0.67 (V2B1), and 1.29 (V2B2). V1 showed increased Streptococcus agalactiae, Peduvirus, and Imidazopyrimidines; V2B1 had higher CAG_127sp900553925, nickel (Ni), and benzene derivatives; V2B2 exhibited elevated Citrobacter farmeri, Svunavirus, arsenic, and organic sulfonic acids. Gut disease prediction model was more accurate after virus typing (86.54% of accuracy in V2B2 subtype; 73.33% of accuracy without typing). These results suggest that integrating enteroviral and bacterial subtypes offers a more precise framework for CRC identification than bacterial-based typing alone.