BMC Cancer[JOURNAL]
Sun
200 papers
Upregulation of NFS1 and downregulation of GSDMD as prognostic biomarkers in acute myeloid leukemia: implications for diagnosis and therapeutic strategies.
Radwan SM, Mostafa D, Radwan RA … +3 more , Elghobary HA, Elghamry WR, Kamal AM
BMC Cancer · 2026 Jun · PMID 42265630 · Full text
BACKGROUND: Despite advances in the treatment of Acute Myeloid Leukemia (AML), the predictive 5-year overall survival rate is still poor not exceeding 20%. Most patients develop relapse partly due to resistance mechanism...
BACKGROUND: Despite advances in the treatment of Acute Myeloid Leukemia (AML), the predictive 5-year overall survival rate is still poor not exceeding 20%. Most patients develop relapse partly due to resistance mechanisms to classical cell death programs. Currently, cytogenetic markers play a crucial role in the early diagnosis, prognostic classification, and therapy selection for AML. Yet, there is a pressing need for the discovery of novel AML biomarkers for a better understanding of the disease's molecular mechanisms, diagnosis, prognosis assessment, and personalized therapeutic response. The role of cell death-related genes in driving AML progression and spread remains inadequately explored. Among these, ferroptosis and pyroptosis are emerging as critical mechanisms of programmed cell death that are often dysregulated in cancer. METHODS: We recruited 100 newly diagnosed AML patients and 40 healthy matched individuals. Using reverse transcription-quantitative PCR analysis, we assessed the expression levels of NFS1 and Gasdermin D (GSDMD). RESULTS: Our findings revealed significant NFS1 upregulation (P < 0.0001) and GSDMD downregulation (P < 0.0001) in AML patients compared to healthy controls. Following treatment, we observed a significant downregulation of NFS1 expression (P < 0.001) and upregulation of GSDMD (P < 0.001). Furthermore, higher pretreatment levels of NFS1 and lower pretreatment levels of GSDMD correlated with poor prognosis (P < 0.001) and decreased one-year survival (P < 0.001). CONCLUSION: Our study suggests that NFS1 and GSDMD may serve as early diagnostic and prognostic markers in AML, offering potential targets for improved therapeutic strategies.
Meta-analysis reveals pathological complete response benefits from neoadjuvant immuno-chemotherapy combination in patients with HER2-negative breast cancer.
Wei Y, Qi Y, Ge H … +3 more , Zeng C, Li Q, Ma F
BMC Cancer · 2026 Jun · PMID 42260448 · Full text
PURPOSE: This meta-analysis aims to evaluate the pooled pathological complete response (pCR) rate and the relative benefits across different subgroups in human epidermal growth factor receptor 2 (HER2) -negative breast c...
PURPOSE: This meta-analysis aims to evaluate the pooled pathological complete response (pCR) rate and the relative benefits across different subgroups in human epidermal growth factor receptor 2 (HER2) -negative breast cancer treated with immunotherapy. METHODS: Clinical trials for neoadjuvant immunotherapy in combination with chemotherapy were identified. The pooled pCR rate of total population and patients across different subgroups was performed. RESULTS: Totally, the meta-analysis included 15 clinical trials comprising 3,885 patients. The pooled pCR rate was 58% (95% CI, 54-62) for triple-negative breast cancer (TNBC) patients and 25% (95% CI, 22-27) for hormone receptor (HR)-positive/HER2-negative (HR+HER2-) patients, respectively. However, the relative benefit of neoadjuvant chemotherapy combined with immunotherapy compared to chemotherapy was comparable (p = 0.70), with odds ratio (OR) of 1.76 (95% CI, 1.43-2.17) in TNBC patients and 1.87 (95% CI, 1.49-2.36) in HR+HER2- patients. Subgroup analysis showed that programmed cell death ligand-1 (PD-L1)-positive patients had higher pCR benefits compared to PD-L1-negative patients, regardless of whether it was immunotherapy combined with neoadjuvant chemotherapy or neoadjuvant chemotherapy alone, with OR of 3.41 (2.61-4.45) and 2.48 (1.80-3.42) respectively. Conversely, among patients receiving chemotherapy alone, the pCR rate in lymph node-positive cases was 42% lower than that in lymph node-negative cases, while the addition of immunotherapy enabled lymph node-positive patients to achieve a comparable pCR rate to lymph node-negative patients (OR, 1.08). CONCLUSION: Immunotherapy showed substantial benefits in improving pCR rates in both TNBC and HR+HER2- patients when combined with neoadjuvant chemotherapy, especially in lymph node-positive breast cancer patients.
Evidence for the prognostic value of TP53 mutations in circulating tumor DNA across solid malignancies: a systematic review and meta-analysis.
Jinyan L, Yibin L, Jiangkui Q … +6 more , Shanbo H, Deng G, Sun C, Yongyu H, Gang H, Tingzhuang Y
BMC Cancer · 2026 Jun · PMID 42260443 · Full text
BACKGROUND: The purpose of this meta-analysis study is to provide evidence for the clinical utility of TP53 mutations in circulating tumor DNA (ctDNA) as a prognostic biomarker. METHODS: We searched the PubMed, Embase, C...
BACKGROUND: The purpose of this meta-analysis study is to provide evidence for the clinical utility of TP53 mutations in circulating tumor DNA (ctDNA) as a prognostic biomarker. METHODS: We searched the PubMed, Embase, Cochrane, and Web of Science databases (last update May 2025) for studies on TP53 mutations in ctDNA or cfDNA as prognosis overall survival and in solid tumors. A total of 21 studies that met the criteria were utilized and data was collected regarding the authors, year of publication, study design, site of the study, number of patients, detection, mutation sample size and outcome measures were collected. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the study, and meta-analysis was done by using STATA 16.0. Effect sizes were in the form of hazard ratios (HR) that had 95% confidence intervals (CI). The models used were fixed-effects and random-effects based on heterogeneity. Funnel plots, and Egger's test was used to measure publication bias, and sensitivity analysis conducted through a leave-one-out method. RESULTS: A total of 21 studies (2,685 TP53-mutated patients, one unreported) showed: Mutated patients had worse progression-free survival (PFS) (HR=2.10, p=0.000; 12 studies, heterogeneity resolved after excluding Yoshida 2023), shorter OS (HR=1.74, p=0.014; 9 studies), and reduced DFS (HR=1.73, p=0.007; 3 studies), but RFS (2 items) showed no statistically significant differences. Subgroup analyses revealed: Prospective studies showed stronger PFS (HR=2.14 vs retrospective 1.90) with Japanese subgroup HR=4.90; Lung/liver cancers had higher HRs than breast. Prospective OS HR=2.25 (lung 3.14, endometrial 0.75). Retrospective DFS HR=1.89 vs Japanese breast RFS HR=4.00. Heterogeneity originated from study design, region, and cancer type variations, with no significant publication bias (Egger's test p>0.05). CONCLUSION: Current evidence suggests that TP53 mutations detected in ctDNA are significantly associated with poor prognosis in various solid tumors, particularly lung cancer. The association is robust for PFS and OS, though high heterogeneity and biological complexity warrant cautious interpretation. These findings support the potential incorporation of ctDNA-based TP53 mutation status into clinical prognostic assessment systems as an adjunctive parameter; however, further standardization of detection protocols, functional annotation of mutation types (e.g., LOF vs. GOF), incorporation of VAF and clonality analysis, and validation in large prospective multicenter cohorts are needed before routine clinical implementation. PROSPERO REGISTRATION NUMBER: CRD420251021095.
Screening and identification of biomarkers in tumor-educated platelets for non-small cell lung cancer.
Xu Z, Li W, Yu Y … +2 more , Wu H, Zhang L
BMC Cancer · 2026 Jun · PMID 42260432 · Full text
BACKGROUND: Platelets, a crucial source of liquid biopsy samples, play a significant role in the progression of various malignancies, including non-small cell lung cancer (NSCLC). However, specific biomarkers for early-s...
BACKGROUND: Platelets, a crucial source of liquid biopsy samples, play a significant role in the progression of various malignancies, including non-small cell lung cancer (NSCLC). However, specific biomarkers for early-stage NSCLC have not yet been identified. In this study, we employed bioinformatics approaches to identify differentially expressed genes (DEGs) in tumor-educated platelets (TEPs) from NSCLC. Subsequently, we validated these genes using specimens from patients with early-stage lung cancer, highlighting their potential as biomarkers for NSCLC. METHODS: We analyzed the platelet mRNA expression profile microarray dataset GSE89843, which comprises samples from NSCLC patients and healthy controls. Utilizing R software, we eliminated batch effects and identified DEGs. NSCLC-associated module genes were identified via weighted gene co-expression network analysis (WGCNA). Enrichment analysis was performed using R-based tools, and protein-protein interaction (PPI) analysis was conducted to identify key DEGs. Finally, RT-qPCR validation was performed to assess the differential expression of selected genes in platelet total RNA between early-stage NSCLC patients and healthy controls. RESULTS: Initially, we analyzed the RNA sequencing data from dataset GSE89843, which contains 779 platelet samples, and identified 532 DEGs (72 upregulated and 460 downregulated). Among these DEGs, seven key genes were identified: HSP90AB1, NPM1, CD44, HSPA4, CD74, SEC31A, and EIF2S1. Notably, CD44 served as the interaction starting point in gene association networks. Meanwhile, HSP90AB1, NPM1, and CD74 exhibited low expression levels in NSCLC. RT-qPCR validation confirmed that HSP90AB1, NPM1, CD44, and CD74 exhibited significantly downregulated expression in platelets from early-stage (I and II) NSCLC patients. CONCLUSION: Specific DEGs for NSCLC are present in platelets, including HSP90AB1, NPM1, CD44, and CD74, which may play a role in the early stages of NSCLC development. These genes exhibit a specific expression pattern, characterized by downregulation in early-stage (I and II) NSCLC, indicating their potential as biomarkers for early screening and diagnosis of NSCLC.
Prognostic significance and optimal staging of supraclavicular lymph node metastasis in upper esophageal squamous cell carcinoma undergoing chemoradiotherapy.
Zhang B, Zhang H, Zheng H … +10 more , Xie X, Ye D, Zhu L, Kang M, Xiao L, Chen Y, Xia W, Dai Y, Wang Y, Zhou J
BMC Cancer · 2026 Jun · PMID 42260426 · Full text
BACKGROUND: The optimal staging of supraclavicular lymph node metastasis (SCLNM) in upper esophageal squamous cell carcinoma (UESCC) remains debated. This study aimed to evaluate its prognostic significance and clinical...
BACKGROUND: The optimal staging of supraclavicular lymph node metastasis (SCLNM) in upper esophageal squamous cell carcinoma (UESCC) remains debated. This study aimed to evaluate its prognostic significance and clinical implications in patients treated with definitive chemoradiotherapy. METHODS: This study included 435 newly diagnosed UESCC patients who received definitive chemoradiotherapy between January 2013 and October 2022. Survival and prognostic factors were analyzed by Kaplan-Meier and Cox regression methods. RESULTS: SCLNM was diagnosed in 49 patients (11.3%) and was strongly associated with metastasis at stations 101, 106rec, 106pre, and 106tb. Multivariate analysis confirmed SCLNM as an independent prognostic factor. Patients with SCLNM had poorer survival than those with M0 disease but better than those with other distant metastases (median overall survival: 24.0 vs. 67.0 vs. 8.0 months). Survival was significantly lower in SCLNM patients compared to N0M0 (P < 0.001) and N1M0 (P = 0.004) patients, but no significant difference was observed compared to N2M0 (P = 0.477) or N3M0 (P = 0.204) patients. After reclassifying SCLNM as a regional lymph node metastasis, N1 patients with SCLNM exhibited worse overall survival than those without SCLNM, although the statistical significance was marginal (P = 0.048); however, this difference was not seen in N2 or N3 categories. In the revised staging system where SCLNM was assigned to N2 or higher, survival differentiation across stages became more distinct, yielding a higher prognostic accuracy compared to the current AJCC staging system. CONCLUSIONS: SCLNM in UESCC patients undergoing definitive CRT shows prognostic similarity to N2-3 disease, but this finding is preliminary and requires further validation.
Real-world effectiveness of mecapegfilgrastim for prophylaxis in patients with breast cancer receiving 2-weekly and 3-weekly chemotherapy in China.
Shi Y, Fu P, Wang Y … +16 more , Li Y, Yao Y, Li H, Yu Z, Song L, Zhang G, Ren Z, Cheng G, Ding L, Yang J, Zhang J, Bie J, Yuan C, Wang Z, Xu Y, Ma J
BMC Cancer · 2026 Jun · PMID 42260418 · Full text
BACKGROUND: Breast cancer patients receiving myelosuppressive chemotherapy are at high risk of febrile neutropenia (FN). Long-acting G-CSFs are recommended for FN prevention, but evidence for mecapegfilgrastim in the dos...
BACKGROUND: Breast cancer patients receiving myelosuppressive chemotherapy are at high risk of febrile neutropenia (FN). Long-acting G-CSFs are recommended for FN prevention, but evidence for mecapegfilgrastim in the dose-dense setting remains limited. METHODS: This multicenter, prospective, observational, real-world study was conducted at 43 centers in China. Patients with breast cancer who received 2-weekly or 3-weekly chemotherapy with mecapegfilgrastim (6 mg) as prophylaxis for chemotherapy-induced neutropenia were enrolled. The primary outcome was the incidence of FN, defined as an oral temperature of > 38.3 °C or two consecutive readings of > 38.0 °C for 2 h and an absolute neutrophil count (ANC) of < 0.5 × 10/l, or expected to fall below 0.5 × 10/L. The secondary outcomes included severe neutropenia and adverse events (AEs). RESULTS: Between June 2019 and March 2022, a total of 757 patients were enrolled. After 1:2 propensity score matching, 36 patients were included in the 2-weekly group and 71 patients were included in the 3-weekly group. In the first cycle, FN, grade 3/4 neutropenia, and grade 4 neutropenia occurred in 0 (0%; 95% CI, 0.0-9.6%), 9 (25.0%; 95% CI, 13.8-41.1%), and 4 (11.1%; 95% CI, 4.4-25.3%) patients in the 2-weekly group, and in 2 (2.8%; 95% CI, 0.8-9.7%), 11 (15.5%; 95% CI, 8.9-25.7%), and 5 (7.0%; 95% CI, 3.0-15.4%) patients in the 3-weekly group. Across all cycles, the corresponding incidences were observed in 0 (0.0%), 11 (30.6%), and 5 (13.9%) patients in the 2-weekly group, and 2 (2.8%), 14 (19.7%) and 7 (9.9%) patients in the 3-weekly group. Dose hold (≥ 5 days) occurred in 7 patients (19.4%) in the 2-weekly group and 5 patients (7.0%) in the 3-weekly group. The incidence of grade 3/4 treatment-emergent adverse events (TEAEs) was 26.7% in the 2-weekly and 33.3% in the 3-weekly groups. No patients had serious AEs in either group. No treatment-related deaths were reported. CONCLUSION: Mecapegfilgrastim was associated with a low incidence of FN and manageable safety profiles in patients with breast cancer receiving 3-weekly or 2-weekly chemotherapy. Nevertheless, further studies with larger sample sizes are warranted to confirm these findings.
Integrated multi-omics profiling uncovers the epigenetic, transcriptional, and metabolic landscape of prostate cancer progression.
Pedersen CA, Wess M, Andersen MK … +5 more , Midtbust E, Sharma A, Fleischer T, Rye MB, Tessem MB
BMC Cancer · 2026 Jun · PMID 42260416 · Full text
A comprehensive understanding of the underlying molecular mechanisms of prostate cancer is essential for the development of precise diagnostic biomarkers. In this study, we applied the unsupervised multi-omics factor ana...
A comprehensive understanding of the underlying molecular mechanisms of prostate cancer is essential for the development of precise diagnostic biomarkers. In this study, we applied the unsupervised multi-omics factor analysis framework (MOFA) to integrate DNA methylation, gene expression, and metabolic profiles derived from the same individuals, aiming to characterize the biological landscape of normal, malignant, and aggressive prostate tissue. Our analysis identified distinct molecular pathways associated with aggressive disease, specifically those involved in zinc metabolism, cell cycle regulation, smooth muscle architecture, immune activation, and tissue morphology. Key metabolites within the TCA cycle, amino acid metabolism, and lipid pathways were central to these signatures. Furthermore, we observed a consistent co-enrichment of SP1 and CTCFL binding regions among factor-associated CpGs, suggesting a model of global epigenetic reprogramming. These findings indicate a novel interplay between Polycomb deregulation, CTCFL-mediated chromatin remodeling, and SP1-driven transcriptional activation in shaping the prostate cancer epigenome. Apart from immune activation, the identified molecular signatures were validated in the TCGA cohort and demonstrated significant predictive value for disease recurrence. Overall, these results underscore the power of multi-omics integration in providing a holistic understanding of prostate cancer biology and its potential for clinical translation into prognostic biomarkers.
Upregulation of miR-32 in tissue and plasma and its association with PTEN expression in colorectal cancer.
Mehrjoei B, Tahmasebi S, Haghnazari L … +3 more , Rezvani P, Bashiri H, Rezvani N
BMC Cancer · 2026 Jun · PMID 42260415 · Full text
BACKGROUND: Early detection of colorectal cancer (CRC) is critical for improving patient outcomes. MicroRNAs (miRNAs) function as post-transcriptional regulators and have emerged as potential minimally invasive diagnosti...
BACKGROUND: Early detection of colorectal cancer (CRC) is critical for improving patient outcomes. MicroRNAs (miRNAs) function as post-transcriptional regulators and have emerged as potential minimally invasive diagnostic biomarkers. Although miR-32 has been implicated in tumor progression in several malignancies, its expression pattern in CRC tissue and plasma and its association with PTEN expression require further clarification. MATERIALS AND METHODS: Expression levels of miR-32 and PTEN were measured using quantitative real-time PCR (qRT-PCR) in tumor tissues, adjacent normal tissues, and plasma samples from 55 CRC patients and plasma samples from 55 age and sex matched healthy controls. RESULTS: MiR-32 expression was significantly upregulated in CRC tissues and plasma samples, whereas PTEN expression was significantly reduced in tumor tissues (P < 0.001). ROC curve analysis demonstrated strong diagnostic performance of miR-32 in tissue (AUC = 0.942) and good performance in plasma (AUC = 0.846). An inverse association between miR-32 and PTEN expression was observed. Higher miR-32 levels were also associated with advanced tumor stage. CONCLUSIONS: This is the first report of concurrent miR-32 upregulation and PTEN downregulation in both CRC tissue and plasma. MiR-32 may represent a potential non-invasive biomarker candidate for CRC detection and disease stratification. However, these findings are observational and require validation in larger, multicenter cohorts and functional studies before clinical application.
Assessing predictors of brachytherapy utilization among cervical cancer patients in Nigeria: evidence from a tertiary cancer centre.
Adegboyega B, Balogun O, Ogunmuyiwa J … +8 more , Habeebu M, Ibeleme O, Ojiebun E, Abraham O, Oshikanlu B, Andero T, Khaw P, Jhingran A
BMC Cancer · 2026 Jun · PMID 42260414 · Full text
BACKGROUND: Brachytherapy is required for curative management of cervical cancer, but it is resource-intensive and technically challenging. There is limited data describing brachytherapy utilisation and its predictive fa...
BACKGROUND: Brachytherapy is required for curative management of cervical cancer, but it is resource-intensive and technically challenging. There is limited data describing brachytherapy utilisation and its predictive factors influencing it in low- and middle-income countries, including Nigeria. This study assessed the trend of brachytherapy utilisation and its predictors among cervical cancer patients in Nigeria. METHODS: We conducted a retrospective study of patients treated for cervical cancer (stage I-IVA) at Medserve-LUTH Cancer Centre between March 2021 and June 2024. Sociodemographic, clinical, and disease-related variables were summarized using descriptive statistics. Univariable and multivariable logistic regression models were used to identify predictors of brachytherapy utilization. RESULTS: Among the 343 patients, average age was 57.82 ± 11.77 years, 242 (70.55%) had stage II or III disease, and 173 (50.43%) received brachytherapy. Age, religion, disease stage, employment status, abdominopelvic pain at presentation, treatment delay, and menopausal state were significantly associated with brachytherapy utilization on univariable analysis (all p < 0.05). Women with increasing age, advanced disease, abdominopelvic pain at presentation, longer treatment delay, and who were Muslims had lower odds of brachytherapy utilization, while employed or premenopausal women had higher odds. On multivariable logistic regression, increasing age (p = 0.005, OR = 0.953, 95% CI = 0.921-0.986), religion (p = 0.003, OR = 0.346, 95% CI = 0.171-0.701), and treatment delay (p = 0.037, OR = 0.929, 95% CI = 0.868-0.996) remained independent predictors of lower brachytherapy utilization. CONCLUSION: This study shows disparities in brachytherapy utilization and suggests that religious beliefs and treatment delay limit access to curative treatment. These disparities may be addressed by intensifying education about early screening, early presentation, and adherence to treatment, especially in religious settings and among religious leaders. However, further studies need to be carried out on a larger population.
Efficacy and safety analysis of TACE combined with lenvatinib and icaritin in unresectable hepatocellular carcinoma with poor performance status.
Lu H, Liang B, Zheng C … +2 more , Cao Y, Xia X
BMC Cancer · 2026 Jun · PMID 42260409 · Full text
OBJECTIVE: To investigate the efficacy and safety of transarterial chemoembolization (TACE) combined with lenvatinib and icaritin in the treatment of patients with unresectable hepatocellular carcinoma (uHCC) with poor p...
OBJECTIVE: To investigate the efficacy and safety of transarterial chemoembolization (TACE) combined with lenvatinib and icaritin in the treatment of patients with unresectable hepatocellular carcinoma (uHCC) with poor physical condition, aiming to provide a safer and more effective treatment strategy for patients with advanced uHCC and poor physical status. MATERIALS AND METHODS: Clinical data from 49 patients with uHCC and poor physical condition who received treatment between June 2022 and December 2023 were collected. The patients were divided into two groups based on their treatment method: TACE + LEN+Icaritin group (N = 21) and TACE group (N = 28). The primary endpoints were the objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS) of the tumor in both groups. The secondary endpoint was the incidence of treatment-related adverse events (AEs) in both groups. RESULTS: The ORR and DCR of the TACE + LEN+Icaritin group were significantly higher than those of the TACE group (66.7% vs. 28.6%, P = 0.011; 85.7% vs. 53.6%, P = 0.030). The mPFS of the TACE + LEN+Icaritin group was longer than that of the TACE group (8.6 months vs. 4.1 months, HR = 0.316, 95%CI: 0.166-0.599; P < 0.001). The incidence of hand-foot syndrome (all grades) was higher in the TACE + LEN+Icaritin group compared to the TACE group (P = 0.004), but there was no significant difference in the incidence of grade 3/4 hand-foot syndrome between the two groups (P = 0.429). The incidence of fatigue and anorexia (all grades) was lower in the TACE + LEN+Icaritin group compared to the TACE group (P < 0.05). A total of 66.7% of patients in the TACE + LEN+Icaritin group showed improvement in physical condition after treatment, which was significantly higher than in the TACE group (P = 0.022). CONCLUSION: TACE combined with lenvatinib and icaritin demonstrates good efficacy and safety in the treatment of patients with uHCC and poor physical condition (ECOG = 2). This combination therapy may be a viable option for improving prognosis and quality of life in patients with uHCC and poor physical condition.
EVX2 methylation assay enables risk assessment of cervical cancer in high-risk HPV-infected individuals.
Wu J, He W, Zhang W … +5 more , Ye D, Cui WZ, Li Y, Luo M, Wang W
BMC Cancer · 2026 Jun · PMID 42260403 · Full text
BACKGROUND: Stratifying cancer risk in high-risk human papillomavirus (hr-HPV) infected individuals can effectively reduce colposcopy referrals and minimize invasive procedures. Current assay methods need to be improved...
BACKGROUND: Stratifying cancer risk in high-risk human papillomavirus (hr-HPV) infected individuals can effectively reduce colposcopy referrals and minimize invasive procedures. Current assay methods need to be improved and perfected. METHODS: Four methylation markers (ZNF135, EVX2, MARCHF11, and UBD) were identified to discriminate cervical cancer (CC) from normal mucosal tissues through the analysis of TCGA/GEO cohorts. Subsequently, a specific methylation marker (EVX2) was further identified via immunohistochemical (IHC) assays and an extensive literature review. After validating the applicability of this technique for EVX2 methylation detection via MALDI-TOF mass spectrometry, a methylation model was constructed based on the selected markers in a retrospective cohort of cervical exfoliated cells (n = 104) and validated in an independent cohort (n = 22) using the identical technique and random forest algorithm. The diagnostic performance was systematically compared with LCT and high-oncogenicity HPV16/18 testing. RESULTS: Four methylation markers (ZNF135, EVX2, MARCHF11, and UBD) were identified that could discriminate CC from normal squamous epithelia. Among these markers, EVX2 was further pinpointed as the key candidate based on gene expression and literature review. A diagnostic model constructed via EVX2 methylation status exhibited robust diagnostic performance in differentiating patients with squamous intraepithelial lesion (SIL) or CC from healthy normal controls, and its diagnostic efficacy was significantly superior to that of LCT and HPV16/18 assays (AUC: 0.95 vs. 0.85 for LCT and 0.57 for HPV16/18 testing). This superiority was more pronounced in detecting HSIL and CC, with a detection rate of 96.97% versus 57.14% (LCT) and 37.5% (HPV16/18 testing). Subsequent analyses of TCGA databases further validated the diagnostic value of EVX2 methylation in CC. CONCLUSIONS: EVX2 methylation detection via MALDI-TOF mass spectrometry reliably discriminates normal squamous epithelium from HSIL and above cervical malignant lesions, and may serve as a rapid, non-invasive, and promising tool for cancer-risk screening and triage in hr-HPV-positive patients.
Integrating DNA methylation and clinical features to predict prostate cancer prognosis.
Qian Y, Zhu W, Fang Z … +14 more , Luo Z, Xie W, Cao Y, Chen W, Fu H, Peng J, Zhang L, Lei S, Jin J, Li J, Zhao X, Gong Z, Zhang D, He Y
BMC Cancer · 2026 Jun · PMID 42260380 · Full text
This study investigates the relationship between DNA methylation patterns and clinicopathological characteristics in prostate cancer. We performed targeted next-generation sequencing (NGS) on methylation sites linked to...
This study investigates the relationship between DNA methylation patterns and clinicopathological characteristics in prostate cancer. We performed targeted next-generation sequencing (NGS) on methylation sites linked to prostate cancer and calculated the corresponding methylation rates. Clinical samples were divided into training and prediction sets. In the training set, we utilized unsupervised clustering and Support Vector Machine (SVM) modeling to distinguish between prostate cancer and non-cancer samples. For predictions, K-Nearest Neighbors (KNN) assessed sample similarity, while SVM facilitated classification. Bayesian methods integrated probabilities to predict cancer status and cluster assignments. To address uncertainties identified by Uniform Manifold Approximation and Projection (UMAP), we validated our results using Random Forest Support Vector Machine (RFSVM), which highlighted significant methylation sites for SVM training. Depth-correction methods were applied to mitigate variations in sequencing depth.In the training dataset, the leave-one-out cross-validation (LOOCV) prediction accuracy of RFSVM was 0.85 (AUC: 0.91); for RFSVM-depth, it was 0.83 (AUC: 0.93). The LOOCV prediction accuracy for Bayesian SVM (BSVM) was 0.87 (AUC: 0.94), decreasing to 0.83 (AUC: 0.91) with depth correction. In the test dataset, our Bayesian prediction achieved an accuracy of 0.8793 (sensitivity: 0.8182, specificity: 0.9167), which improved to 0.9655 with depth correction (sensitivity: 1.0, specificity: 0.9444). RFSVM demonstrated an accuracy of 0.8621 (sensitivity: 0.8182, specificity: 0.8889), dropping to 0.7759 with depth correction. Among 58 samples, predictions showed 67% complete consistency, with 84% consistency in methylation rates and 78% in specific methylation sites. Figure 6 presents a comprehensive comparison of the performance of RFSVM, BSVM, XBSVM, and RFESVM on training and test datasets, including feature selection and prediction consistency. Confusion matrices, ROC curves, and Venn diagrams were used to detail the feature importance and prediction consistency of each method.These findings highlight the importance of analyzing individual methylation sites and broader methylation patterns in understanding the role of DNA methylation in prostate cancer, providing valuable insights into the effects of data preprocessing and feature selection.
High-risk cytogenetic abnormalities impact the cytological and clinical behavior of core binding factor acute myeloid leukemia: a case-control study.
El Achkar H, Bazarbachi A, Chakhachiro Z … +2 more , Mahfouz R, Assaf N
BMC Cancer · 2026 Jun · PMID 42252425 · Full text
BACKGROUND: Despite its classification as acute myeloid leukemia (AML) with favorable prognosis, core binding factor AML (CBF-AML) with t(8;21)/inv(16) exhibits clinical heterogeneity with varying remission and relapse r...
BACKGROUND: Despite its classification as acute myeloid leukemia (AML) with favorable prognosis, core binding factor AML (CBF-AML) with t(8;21)/inv(16) exhibits clinical heterogeneity with varying remission and relapse rates. Newly emerging data suggest a modulatory effect of additional cytogenetic abnormalities on the clinical behavior of CBF-AML, with high-risk anomalies negatively affecting survival. METHODS: Aiming at validating these observations, we compare the pathological and clinical characteristics of CBF-AML patients with high-risk additional cytogenetic abnormalities (HR-ACAs) to CBF-AML without HR-ACAs. RESULTS: The 14-year retrospective review of the laboratory and clinical data of 535 AML patients diagnosed at our institution shows that 37% of CBF-AML patients carry at least one secondary cytogenetic abnormality. HR-ACAs, primarily complex karyotypes, constituted 38% of secondary abnormalities. Interestingly, patients with HR-ACAs more frequently presented with cytopenia, and exhibited more aggressive clinical courses. The detection of HR-ACAs was found to be associated with higher relapse rates (50% vs. 18%;p = 0.006), a greater requirement for stem cell transplantation (89% vs. 27%;p = 0.001), and higher death rates (63% vs. 17%;p = 0.008). CONCLUSION: These results indicate that the presence of HR-ACAs impacts the cytological and clinical features of CBF-AML. This entity thus deserves distinct considerations for risk stratification and therapeutic options.
Pharmacovigilance of carmustine: distinct neurotoxic and systemic safety signals identified in FAERS.
Xu K, Guo M, Dong H … +2 more , Cai M, Xu P
BMC Cancer · 2026 Jun · PMID 42252424 · Full text
BACKGROUND: Carmustine (BCNU), a nitrosourea alkylating agent, is used in malignant gliomas, lymphomas, and hematopoietic stem cell transplantation. Although its major toxicities are recognized, comprehensive postmarketi...
BACKGROUND: Carmustine (BCNU), a nitrosourea alkylating agent, is used in malignant gliomas, lymphomas, and hematopoietic stem cell transplantation. Although its major toxicities are recognized, comprehensive postmarketing evidence on the broader spectrum of carmustine related adverse event signals remains limited. This study evaluated carmustine related reporting signals using real world pharmacovigilance data. METHODS: Adverse drug reaction (ADR) reports identifying BCNU as the primary suspect were extracted from the FDA Adverse Event Reporting System (FAERS, Q1 2004-Q1 2024). Disproportionality analyses using reporting odds ratio (ROR), proportional reporting ratio (PRR), information component (IC), and empirical Bayesian geometric mean (EBGM) were performed at both system organ class (SOC) and preferred term (PT) levels, with stratification by sex. RESULTS: In total, 718 BCNU reports with 3,091 preferred terms were analyzed. Significant signals emerged for nervous system disorders (ROR = 2.74), blood and lymphatic system disorders (ROR = 2.95), and infections (ROR = 2.15). At the PT level, eosinophilic meningitis, pneumocephalus, and intracranial hypotension showed strong disproportional reporting signals among carmustine related reports. Descriptive sex stratified reporting patterns were observed, including intracranial hypotension in female reports and pseudomeningocele in male reports. CONCLUSION: Carmustine related FAERS reports showed distinct neurotoxic, hematologic, and procedural reporting patterns, some with descriptive sex specific differences. These findings emphasize the need for continued post-marketing surveillance to inform clinical practice and optimize risk mitigation.
UBA1 drives cell cycle to promote malignancy and serves as a therapeutic target in Ewing Sarcoma.
Yu S, Jiang R, Zhou L … +4 more , Wu A, Wei H, He S, Xiao J
BMC Cancer · 2026 Jun · PMID 42251322 · Full text
BACKGROUND: Ewing sarcoma (ES) is an aggressive malignancy with high metastatic potential and poor prognosis, necessitating novel biomarkers and therapeutic targets. This study investigates the role of the ubiquitin-acti...
BACKGROUND: Ewing sarcoma (ES) is an aggressive malignancy with high metastatic potential and poor prognosis, necessitating novel biomarkers and therapeutic targets. This study investigates the role of the ubiquitin-activating enzyme E1 (UBA1) in ES pathogenesis and its clinical relevance. METHODS: Bioinformatic analysis of GEO datasets was performed. UBA1 expression was validated in clinical samples and ES cell lines (A673, RDES) via Western blot and qPCR. To investigate the functional role and therapeutic potential of UBA1 in ES, we performed siRNA-mediated knockdown followed by a series of in vitro functional assays, including assessments of proliferation, colony formation, migration, invasion, cell cycle distribution, and EdU incorporation. Mechanistic studies were subsequently conducted through the WB experiment. In vivo experiments were carried out using a xenograft mouse model to evaluate the effect of UBA1 depletion on tumor growth. Additionally, the UBA1-specific inhibitor TAK-243 was used to assess the therapeutic potential of targeting UBA1. RESULTS: UBA1 expression was significantly elevated in ES tissues, and high UBA1 levels correlated with poor prognosis. Knockdown of UBA1 suppressed malignant phenotypes, including proliferation, colony formation, migration, and invasion, while inducing cell cycle arrest and inhibiting DNA synthesis. Mechanistically, UBA1 depletion led to dysregulation of the G2/M checkpoint pathway, consistent with Gene Set Enrichment Analysis (GSEA) predictions. In vivo experiments confirmed the oncogenic role of UBA1, and treatment with the UBA1 inhibitor TAK-243 recapitulated the effects observed upon UBA1 knockdown. CONCLUSION: Targeting UBA1 disrupts cell cycle progression and inhibits proliferation in ES, underscoring its therapeutic potential.
An integrated pathway mutation and clinical model predicts survival in unresectable HCC with hepatic arterial infusion chemotherapy combined with lenvatinib and tislelizumab.
Tang S, Cai H, Wu Z … +5 more , Huang S, Zhao L, Wu L, Gong L, Guo W
BMC Cancer · 2026 Jun · PMID 42251311 · Full text
BACKGROUND: Triple combination therapy consisting of hepatic arterial infusion chemotherapy (HAIC), lenvatinib, and tislelizumab has shown encouraging clinical efficacy in patients with advanced hepatocellular carcinoma...
BACKGROUND: Triple combination therapy consisting of hepatic arterial infusion chemotherapy (HAIC), lenvatinib, and tislelizumab has shown encouraging clinical efficacy in patients with advanced hepatocellular carcinoma (HCC). However, robust prognostic models to predict treatment outcomes remain lacking. METHODS: A total of 83 patients with unresectable HCC receiving HAIC combined with lenvatinib and tislelizumab were enrolled to develop a prognostic prediction model, which was subsequently validated in an independent cohort of 26 patients. Underlying mechanisms were investigated using targeted exome sequencing and RNA sequencing. RESULTS: We assessed the cumulative impact of gene mutations and identified three signaling pathways associated with progression-free survival (PFS), namely the Hedgehog, ErbB, and focal adhesion pathways, in patients undergoing triple combination therapy. An integrated prognostic model incorporating these PFS-related pathways and key clinical risk factors-aspartate aminotransferase, Child-Pugh class, and presence of metastasis-was established and validated. Mechanistic analyses demonstrated enrichment of angiogenesis- and hypoxia-related signatures, along with increased immune cell infiltration in responders, providing a biological basis for the observed therapeutic efficacy. CONCLUSION: This integrated prognostic model, combining pathway-level genomic alterations with clinical risk factors, enables reliable prediction of treatment outcomes in patients with unresectable HCC receiving HAIC, lenvatinib, and tislelizumab. It may serve as a valuable tool for guiding personalized therapeutic decision-making.
Early antiretroviral therapy and long-term cancer risk in HIV: 9-year outcomes from the START randomized trial.
Ramaswami R, Nordwall JA, Gilbert D … +6 more , Kitchell E, Timiryasova A, Mitsuyasu R, Phillips AN, Lundgren J, Grabar S
BMC Cancer · 2026 Jun · PMID 42251304 · Full text
BACKGROUND: Antiretroviral therapy (ART) reduces cancer risk in people with HIV (PWH) but the long-term impact of immediate ART initiation on infection-related and infection-unrelated cancers remains unclear. METHODS: In...
BACKGROUND: Antiretroviral therapy (ART) reduces cancer risk in people with HIV (PWH) but the long-term impact of immediate ART initiation on infection-related and infection-unrelated cancers remains unclear. METHODS: In the Strategic Timing of Antiretroviral Treatment (START) trial, 4684 ART-naïve adult PWH with CD4 + T-cell count above 500 cells/mm were randomized to immediate or deferred ART initiation arms (i.e., until CD4 + T-cells below 350 cells/mm). In May 2015, unblinding revealed a 74% reduction in infection-related cancer risk in the immediate arm. Post-2016, participants in the deferred arm were recommended to start ART, and follow-up continued through 2021. This analysis evaluates cancer incidence (by infection-related and infection-unrelated diagnoses) between the treatment arms by time-period (overall, pre-2016 and post-2016). RESULTS: Over a median follow-up of 9 years, 120 participants were diagnosed with cancer. The overall hazard ratio (HR) for cancer risk in the immediate versus deferred arms was 0.50 (95% CI: 0.34 to 0.73; p < 0.001). Pre-2016, the HR (immediate vs. deferred) was 0.33 (95% CI: 0.19 to 0.60; P < 0.001), while post-2016, it was 0.69 (95% CI: 0.42 to 1.13; P = 0.14), and P = 0.062 for the difference. For infection-related cancers in pre-2016 the HR was 0.24 (95% CI: 0.11 to 0.55; P < 0.001) and post-2016, HR was 0.53 (95% CI: 0.23 to 1.18; P = 0.12) and P = 0.18 for the difference. For infection-unrelated cancers, there was no significant difference in HR between immediate and deferred arms in either time period. CONCLUSION: Immediate ART initiation significantly reduces infection-related cancer risk in PWH that persists long-term. CLINICAL TRIAL REGISTRATION: NCT00867048.
B7-H3 membranous expression correlates with histological grading in a two-center cohort of 133 pre-treatment bone and soft tissue sarcoma samples.
Kloker LD, Rottscholl R, Heitmann JS … +5 more , Bronsert P, Braig D, Benzler K, Zender L, Deinzer CKW
BMC Cancer · 2026 Jun · PMID 42251292 · Full text
BACKGROUND: B7-H3 targeted therapies are an upcoming promising treatment option for a variety of solid tumors. High levels of B7-H3 expression have only been reported for a few sarcoma subtypes in previous studies, but a...
BACKGROUND: B7-H3 targeted therapies are an upcoming promising treatment option for a variety of solid tumors. High levels of B7-H3 expression have only been reported for a few sarcoma subtypes in previous studies, but a systematic analysis in an untreated sarcoma cohort and across many different sarcoma subtypes has not yet been conducted. METHODS: One hundred thirty-three sarcoma samples of previously untreated patients from different sarcoma entities including soft tissue sarcoma (STS, n = 103) and bone sarcoma (BS, n = 30) were collected from two sarcoma centers in South-West Germany. Samples were centrally immunohistochemically stained and assessed for membranous B7-H3 expression. For further analysis of B7-H3 expression, H-Scores were calculated. Baseline characteristics such as sex, age, histology, grading, staging as well as outcome data like treatments, event-free and overall survival were collected. RESULTS: B7-H3 was found to be broadly expressed (97%) across all tested sarcoma subtypes, with only four samples (3%) without B7-H3 expression. 45% of all samples had low (H-Score 1-100), 33% intermediate (H-Score 101-200) and 19% high (H-Score 201-300) membranous B7-H3 expression. Highest expression was found in pleomorphic liposarcoma (median 202.5), osteosarcoma (median 175) and angiosarcoma (median 167.5), whereas expression was lowest in myxoid and well differentiated liposarcoma (medians 44.5 & 62.5) and chondrosarcoma (median 60). H-Scores were found to significantly correlate positive with histological grading irrespective of histological sarcoma subtype. Pre-treatment B7-H3 H-Scores did predict event-free but not overall survival. CONCLUSIONS: B7-H3 is a promising treatment target in sarcomas as it is highly expressed particular in high grade bone and soft tissue sarcomas, such as pleomorphic liposarcomas and osteosarcomas.
Predictive clinicopathologic factors for para-aortic nodal involvement in endometrial carcinoma.
Yalcin Y, Ozerkan K, Yalcin SE
BMC Cancer · 2026 Jun · PMID 42249364 · Full text
BACKGROUND: To identify clinicopathologic risk factors predicting para-aortic lymph node (PALN) metastasis in patients with endometrial carcinoma. METHODS: A retrospective analysis was conducted on 598 patients with FIGO...
BACKGROUND: To identify clinicopathologic risk factors predicting para-aortic lymph node (PALN) metastasis in patients with endometrial carcinoma. METHODS: A retrospective analysis was conducted on 598 patients with FIGO 2009 stage I-III endometrial carcinoma who underwent comprehensive surgical staging, including pelvic and para-aortic lymphadenectomy, at Bursa Uludag University Hospital between January 2000 and May 2025. Demographic, surgical, and histopathological parameters were extracted from medical records. Univariable and multivariable regression analyses were performed to determine predictors of PALN metastasis. RESULTS: PALN metastasis was identified in 64 patients (10.7%). Isolated PALN involvement occurred in 3.5% of cases. On multivariable analysis, elevated preoperative CA-125 (> 35 U/mL) (OR 2.07, 95% CI 1.11-4.84), deep myometrial invasion (> 50%) (OR 2.62, 95% CI 1.09-6.30), lymphovascular space invasion (OR 1.91, 95% CI 1.12-4.75), and pelvic lymph node metastasis (OR 25.5, 95% CI 12.8-50.9) were independently associated with PALN involvement. Patients with pelvic nodal metastasis had a markedly increased likelihood of para-aortic spread. CONCLUSIONS: Para-aortic lymph node metastasis in endometrial carcinoma is independently associated with pelvic lymph node positivity, elevated preoperative CA-125, deep myometrial invasion, and LVSI. These parameters may guide risk stratification and support the development of predictive models to minimize unnecessary lymphadenectomy while ensuring accurate staging and tailored adjuvant therapy.
The prognostic significance of B7-H3 expression in patients with advanced colorectal cancer.
Huang Y, Acuna-Villaorduna A, Gali R … +10 more , Maia C, Cedona K, Zang X, Qi X, Zhang W, Zhang C, Lin J, Liu Q, Maitra R, Goel S
BMC Cancer · 2026 Jun · PMID 42249337 · Full text
BACKGROUND: Biomarkers, particularly prognostic and immune based, are lacking in colorectal cancer (CRC). This study aimed to evaluate the expression of novel immune based biomarkers among patients with CRC to predict cl...
BACKGROUND: Biomarkers, particularly prognostic and immune based, are lacking in colorectal cancer (CRC). This study aimed to evaluate the expression of novel immune based biomarkers among patients with CRC to predict clinical outcomes. METHODS: A CRC tumor microarray (TMA) was developed from a multiracial patient population, and expression of diagnostic markers (CK7, CK20, CDX2) and immune based (HHLA2, B7-H3, PD-L1) determined by immunohistochemistry (IHC) in a novel quantitative manner. Comprehensive clinical information was extracted. Among patients with metastatic (m) cancers, Kaplan Meier curves were plotted, and Cox proportional hazards regression analysis was performed to evaluate association with overall survival (OS). RESULTS: Among 388 patients, 150 had de novo metastatic disease, 108 experienced relapses from localized cancer, and 130 patients had cured localized disease. Racially/ethnically, 70 were non-Hispanic whites (NHW), 159 were non-Hispanic blacks (NHB), 147 Hispanic, and 12 Asian. The median age was 62 years, with a female predominance (53%). Among the patients with metastatic CRC, that included those with relapses and with de novo metastatic CRC (n = 258), in a multivariable Cox proportional hazards model, left sidedness (HR 0.52; 95%CI 0.35 - 0.77, p < 0.001) and low expression of both PD-L1 and B7-H3 was associated with better OS (HR 1.73; 95%CI 1.08-2.76, p = 0.023). CONCLUSION: In this multiracial TMA of CRC, in a robust multivariable model, following REMARK guidelines, we validate our prior findings that low expression of both B7-H3 and PD-L1 is prognostic for OS among patients with mCRC. Given the rapid proliferation of B7-H3 targeted drug development in clinical trials, these findings may help create a platform for future research to delineate their predictive role in a bespoke therapeutic approach.
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