Bladder cancer is characterized by its heterogeneous nature and high propensity for recurrence and progression. The absence of reliable diagnostic and prognostic biomarkers to accurately identify high-risk patients further complicates the clinical management of the disease. MOC-31, an antibody that targets epithelial cell adhesion molecule (EpCAM), is utilized to distinguish between mesothelioma and metastatic cancer, but its clinical utility, prognostic value and functional dynamics in bladder cancer have yet to be verified.

The global incidence of thyroid cancer, particularly papillary thyroid carcinoma (PTC), is rising due to more frequent incidental findings. Despite a high 10-year survival rate of 93%, up to 28% of PTC patients experience locoregional recurrence. Postoperative monitoring typically relies on serum thyroglobulin (Tg), but the presence of anti-thyroglobulin antibodies (TgAb) interferes with Tg measurement, necessitating reliable detection methods. This study aimed to assess the predictive value of postoperative TgAb levels for PTC recurrence and establish a TgAb threshold as a prognostic marker.

Mantle cell lymphoma (MCL) is a rare B-cell Non-Hodgkin-lymphoma that predominantly affects elderly patients. While younger and fit patients receive an intensive first-line treatment, older or comorbid patients have limited options of chemo-immunotherapy (CIT) alone followed by anti-CD20-antibody maintenance. Targeted oral agents as Bruton`s tyrosine kinase inhibitors (BTKi, e.g. ibrutinib) - and B-cell lymphoma 2 (Bcl2) - inhibitors (e.g. venetoclax) have revolutionized the treatment especially for relapsed patients, with apparent synergistic effects. The MCL elderly III trial of the European MCL Network is an international phase II trial evaluating the efficacy of the combination of ibrutinib, venetoclax and rituximab as well as the CIT bendamustine and rituximab in combination with ibrutinib in elderly patients with untreated MCL.

In this paper, the tumor-host interaction is modeled using a Lotka-Volterra framework. The critical parameters that define the possible dynamical regimes are identified through linear stability analysis. The effects of both constant and periodic perturbations are examined, along with their clinical implications. The treatment dose required to drive the system to a desired state is determined. It is also shown that aggressive tumors evolve toward a limit cycle when the host is under the action of low-frequency periodic treatment. As the frequency increases, a transition to a non-chaotic attractor occurs. This transition narrows as the frequency of the external periodic perturbation increases. No chaotic behavior is observed, even at higher values of both perturbation strength and frequency, as the maximum Lyapunov exponent remains negative. These results suggest that although aggressive tumors may not be completely eradicated by conventional anticancer therapies, they could potentially be controlled through external low-frequency periodic treatments that target directly only the host, such as immunotherapy.

The curative surgical treatment of older patients with oral cavity squamous cell carcinoma (OCSCC) is often personalized by incorporating subjective decisions on age and frailty. We aimed to determine here whether real-world recommended treatment, following official French guidelines only, versus deviation from recommended treatment was beneficial for older patients with OCSCC. To do this, we performed a retrospective evaluation of patients >70 years managed for treatment of p16-negative OCSCC in our tertiary hospital center in France between 2007 and 2017. The association between postoperative morbidity and deviation from recommended treatment was analysed using multivariate logistic regression. Cox Proportional Hazards Regression assessed the associations between deviation from recommended treatment and both the hazard of recurrence and mortality within 5 years. We included 185 patients who were recommended surgical resection of OCSCC: n = 147/185 (79%) patients underwent the recommended treatment and 38/185 (21%) patients underwent deviation from recommended treatment. Patients who underwent deviation from recommended treatment had a significantly lower recurrence-free survival (p = 0.0005) and overall survival (p = 0.008). Deviation from recommended treatment was found independently associated with increased development of 3-month postoperative morbidity (adjusted odds ratio 2.63 [1.23-5.82]; p = 0.02) and increased risk of recurrence within 5 years (adjusted hazard ratio 1.79 [1.14-2.83]; p = 0.01). Deviation from recommended treatment was not found independently associated with increased risk of mortality within 5 years (1.35 [0.82-2.23]; p = 0.2). Overall, deviation from recommended treatment was associated with worse outcomes and so we have identified a decision-making process biased by undocumented and subjective evidence. Preoperative risk models therefore require further validation in older patients with OCSCC to define more appropriate treatment regimens.

Lung cancer (LC) is the leading cause of cancer-related mortality worldwide, accounting for millions of deaths annually. Its major subtypes-lung squamous carcinoma (LUSC), lung adenocarcinoma, and small-cell LC-exhibit distinct risk factors and genetic susceptibilities, necessitating the use of subtype-specific biomarkers. Two-sample Mendelian randomization (MR) analyses were conducted using protein quantitative trait loci from the UK Biobank Pharma Proteomics Project and deCODE datasets. A robust analytical framework, including reverse MR, meta-analysis, summary-data-based MR tests, and colocalization, cisMR-cML, MR.CUE and phenotype scanning analyses were used to identify proteins associated with LC risk. We conducted a systematic review to contextualize our research findings. Follow-up analyses, including pathway enrichment, protein-protein interaction network analysis, and druggability evaluations, were used to explore the mechanisms and therapeutic potential of the identified proteins. Significant proteins were validated using population-level proteomic data from the UK Biobank (UKB). The results showed that twenty-five proteins were significantly associated with LC or its subtypes, including 15 novel findings. 60S ribosomal protein L14 (RPL14) and advanced glycosylation end-product-specific receptor (AGER) emerged as the strongest discovery, demonstrating consistent and significant associations across both MR and population-level analyses. RPL14 exhibited positive associations with overall LC risk (MR_meta: odds ratio [OR]: 2.012, 95% confidence interval [CI]: 1.297-3.119; UKB: OR: 1.509, 95% CI: 1.015-2.244). Similarly, AGER showed significant protective effects against LUSC risk (MR_meta: OR: 0.572, 95%CI: 0.368-0.889; UKB: OR: 0.366, 95% CI: 0.158-0.850). Pathway analysis revealed the involvement of these proteins in immune regulation and tumorigenesis. Among the 13 identified druggable targets, RPL14 and AGER showed therapeutic potential as approved or investigational drugs targeting these proteins. These findings offer new insights into the pathogenesis of LC and potential therapeutic targets.

PD-L1 expression for the prediction of response to immune-checkpoint blockade remains the most broadly utilised clinically validated biomarker in a range of tumour types. In this study, we aimed to assess, in a prospectively collected matched cohort, the impact of sampling technique and both formalin and alcohol fixation on PD-L1 expression and heterogeneity in non-small cell lung carcinoma (NSCLC). Patients undergoing surgical resection for NSCLC were consented. Surgical specimens were received directly from theatre and sampled fresh to produce two sets of core biopsies, two fine-needle aspirates (FNAs) and two whole-block tissue sections from each specimen. A matched biopsy, FNA, and whole-block were placed into formalin or an alcohol-based fixative (Cytolyt™) prior to PD-L1 immunohistochemistry assessment. A total of 114 specimens from 57 patients were included. All whole-block cases (100%), 92% of core biopsies, and 88% of FNAs were adequate for PD-L1 expression analysis. Fixation had no significant impact on adequacy, but cytology specimens fixed in alcohol showed a significant reduction in PD-L1 expression, with 25% of cases placed into different clinically relevant categories of PD-L1 expression. PD-L1 expression by immunochemistry is an exemplar of the challenges of utilising a heterogeneously expressed protein-based predictive biomarker. Regardless of sampling technique, a good quality biopsy or FNA is likely to give a statistically representative PD-L1 expression, although expression ranges close to clinically relevant cut-offs of 1% and 50% remain a source of potential discordance.

Molecular targeted therapy and immunotherapy have shown promise in managing gastric adenocarcinoma. The amplified expression of Human epidermal growth factor receptor-2 (HER-2) and microsatellite stable (MSI) status serve as indicators of response to targeted therapy and immunotherapy, respectively.

Brain metastasis represents the most prevalent form of brain tumors in adults, with a rising incidence resulting from significant advancements in cancer detection and therapeutic interventions. Current treatment protocols advocate for whole brain radiotherapy (WBRT) for patients who are not candidates for either surgical resection or stereotactic irradiation. However, cognitive decline remains a major side effect of this treatment modality. Hippocampal-sparing WBRT (HA-WBRT) has been shown to decrease brain toxicity, with the main concern being the probability of developing new brain metastasis in the hippocampal avoidance region.

Recent evidence suggests that EpCAM and CD44 could serve as diagnosis or prognosis markers in pancreatic cancer (PC). In this meta-analysis, we evaluated their associations with clinicopathologic features. Specifically, we compared immunohistochemical-positive and -negative PC patients for T stage (T3-T4 vs. T1-T2), N stage (N1 vs. N0), M stage (M1 vs. M0), tumor grade (well/moderately vs. poorly differentiated), UICC Stage (III, IV vs. I, II), and overall survival (OS). The diagnostic meta-analysis was performed analysing the pooled sensitivity and specificity and evaluating overall accuracy to indicate the diagnostic efficacy of the markers. The protocol of this systematic review and meta-analysis was registered on the PROSPERO website under the registration number of CRD42024568390. A systematic search of PubMed, Scopus, and ISI Web of Science was conducted on January 30th, 2025. The statistical analysis was performed using the Review Manager 5.4 software and R language (R package Mada and Metafor). The quality of the studies included was assessed using the Newcastle-Ottawa scale and the QUADAS-2 tool. Data from relevant studies were independently screened and extracted using Rayyan, by at least two authors. A total of 19 studies were eligible (9 studies for EpCAM, 9 studies for CD44, and 2 studies for both EpCAM and CD44), comprising a total of 1370 patients. The diagnostic meta-analysis demonstrated moderate accuracy for EpCAM (AUC, 95% CI of 0.802, 0.69-0.96). A statistically significant association was found for CD44 expression and T-status (OR = 2.04, 95%CI = 1.18-3.51), or N-stage (OR = 2.68, 95%CI = 1.86-3.85), or TNM stage (OR = 3.79, 95%CI = 2.14-6.71). CD44v6 overexpression predicted worse OS (HR = 2.33, p < 0.00001), while EpCAM + CD44 + co-expression was prognostic (HR = 2.02, p = 0.02). Heterogeneity was not observed among the studies included, but further research is warranted to better understand the clinical implications of these markers' positivity in PC diagnosis and prognosis.

Radiotherapy (RT) is a standard curative treatment for prostate cancer (PCa) and there is growing evidence of the high efficacy of moderate and ultra-hypofractionated RT. Reducing treatment duration to one week or less is a major advance, but very few studies have explored single-fraction therapy. This study evaluates the feasibility, safety, and efficacy of single-fraction stereotactic body RT (SBRT) while delivering the entire procedure in one day, with a potentially high benefit in terms of patient comfort and therapy cost and logistics.

Accurate delineation of Gross Tumor Volume (GTV) in lung cancer is critical for effective radiotherapy and surgical planning. However, segmentation of GTV in high-resolution CT images remains challenging, particularly when tumors are small or have indistinct boundaries.

Microvascular invasion (MVI) is a key risk factor for hepatocellular carcinoma (HCC) recurrence. There is a lack of methods to diagnose MVI preoperatively. The objective of this study was to develop a model for preoperative prediction of MVI in HCC.

Clinical studies demonstrate that comorbidity between colorectal cancer (CRC) and depression is common, leading to a higher mortality risk among CRC patients. However, the mechanisms remain largely unexplored. The role of core brain regions in comorbidity of CRC and depression and whether modulating these regions can improve both depression-like symptoms and CRC progression have yet to be clarified. In this study, we establish a mouse (Mus musculus) model of CRC and observe that mice with orthotopic colorectal cancer (CRC mice) display depression-like behaviors. Through c-FOS mapping, network analysis, correlation analysis, and inverse tracing, we identify the anterior cingulate cortex (ACC) as a central node within the depression-related brain network in CRC mice. Notably, inhibiting ACC activity not only alleviates depression-like behaviors but also mitigates CRC-induced neuronal damage and reduces CRC tumor progression. These findings underscore the critical role of the ACC in comorbidity of CRC and depression and suggest that ACC-targeted interventions may hold therapeutic potential for CRC patients with comorbid depression.

The estimation of the primary site is crucial when considering chemotherapy regimens in cancer of unknown primary (CUP). The task is particularly challenging for poorly differentiated or undifferentiated carcinoma, or unknown histological tumors with unknown primary (U-CUP). Instead of site-specific chemotherapy, a biomarker-guided therapy using genomic testing is required to predict the efficacy of molecular-targeted agents and immune checkpoint inhibitors (ICI). We focused on inactivating the SWI/SNF complex, a chromatin regulatory complex. We investigated the clinical features of CUP with SWI/SNF chromatin remodeling abnormalities and examined whether SWI/SNF chromatin remodeling abnormalities are a predictive marker of ICI efficacy.

Acute Myeloid Leukemia (AML) is a highly heterogeneous malignant hematologic cancer with poor clinical outcome. The presence of leukemia stem cells (LSC) is a significant factor contributing to the failure of AML treatments and frequent relapses. The quiescent and plastic nature of LSC decreases cell death under conventional chemotherapy. Programmed cell death (PCD) plays a critical role in the development and progression of various cancers including AML. We hypothesized that the expression of PCD gene in LSCs may predict the therapeutic outcome of AML patients in the clinic. In this study, we comprehensively analyzed the expression of PCD gene and identified the unique expression patterns of cell death genes of LSC. By integrating PCD- and LSC-related genes, we identified eight LSC death genes with prognostic values: OAZ1, S100A4, MPG, IL2RA, MMRN1, CDK6, HOXA9, and XIRP2. Based on these genes, we developed a leukemia stem cell prognostic death score (LSCD) and a prognostic nomogram. Our findings revealed that LSC, particularly Quiescent LSPC, exhibits a high LSCD score. AML patients with high LSCD score group showed characteristics of significant immune dysfunction and worse prognosis. Additionally, predictions regarding FDA-approved drugs indicated that the high LSCD score group is less sensitive to Venetoclax but more sensitive to Crenolanib, Tandutinib, or Midostaurin. In summary, we developed an LSCD model that shows the predictive potential of clinical prognosis and drug sensitivity. This model provides meaningful insights for personalized treatment of AML patients.

Local treatment of pelvic Ewing Sarcoma (EWS) is czhallenging due to complex anatomy and potential complications. Local therapy may be deferred to maintain chemotherapy dose-intensity, but the impact of this delay on outcomes remains unclear.

Breast cancer has become one of the most common malignant tumors in women, and the incidence rate is increasing annually in men. This study focused on exploring the prognostic significance of the combined detection of serum ALP and LDH in patients with breast cancer. We enrolled 80 individuals with male breast cancer (MBC), female breast cancers (FBCs) were randomly matched via propensity score matching (PSM). In the MBC cohort, the optimal cutoff values for ALP and LDH were determined to be 114 U/L and 207 U/L, respectively, whereas in the FBC cohort, they were 68 U/L and 133 U/L, respectively. There was a difference in median survival between patient groups classified by the optimal cutoff values of ALP and LDH in the FBC cohort. However, in the FBC cohort, there was no significant correlation between the levels of ALP or LDH and patient prognosis. We developed a "joint score" system that incorporates the values of both ALP and LDH and separates MBCs into three groups. Survival was significantly different among the three groups. In the multivariate analysis, the "joint score" was identified as an independent prognostic factor for both disease-free survival(DFS) and overall survival (OS).

The CBFA2T3::GLIS2 (CG) fusion protein causes aggressive pediatric acute megakaryoblastic leukemia (AMKL). Although dysregulated molecular pathways in AMKL have been identified, their role in early pre-leukemic transformation remains poorly understood. We developed a disease model utilizing genetically modified human induced pluripotent stem cells (hiPSC) physiologically and conditionally expressing CG. Using in vitro differentiation and single-cell multi-omics, we captured the impact of oncogene activity on gene-regulatory networks during hematopoiesis. We discovered that CG interferes with myelopoiesis through two alternative routes: by locking aberrant megakaryocyte progenitors (aMKP) in a proliferative state, or by impeding differentiation of aberrant megakaryocytes (aMK). Transcriptionally and functionally, aMKPs mimic CG-AMKL cells and establish a self-renewal network with co-factors GATA2, ERG, and DLX3. In contrast, aMKs partially sustain regulators of MK maturation but fail to complete differentiation due to repression of factors like NFE2, SPI1, GATA1 and LYL1. These insights may inform new strategies for targeting AMKL cell states.

Gastric MALT lymphoma diagnosis relies on histopathological findings and immunoglobulin H gene (IgHr) rearrangement testing, which reflects monoclonal immunoglobulin proliferation. This study aimed to clarify the role of IgHr in the diagnosis, treatment prediction, and surveillance of gastric MALT lymphoma. Of the 152 suspected cases, 131 were definitively diagnosed using a combination of IgHr and pathology, with pathological findings considered the gold standard. Patients with discrepancies between IgHr and pathology underwent re-evaluation. The relationship between IgHr status, clinicopathological features, and treatment outcomes was analyzed. IgHr and histopathology were assessed over 2 years in 41 patients after pathological complete remission (pCR). IgHr positivity was 69.5% at initial biopsy and 90.8% after two biopsies. IgHr-positive cases had higher H. pylori infection rates and better CR rates post-eradication. Patients with IgHr positivity at pCR had higher recurrence rates (16.7%). IgHr positivity gradually declined among 37 non-recurrent cases (CR: 56.8%, 6 M: 45.9%, 1Y: 21.6%, 2Y: 10.8%), indicating a delay between pCR and IgH-negative conversion. Repeated biopsies may improve the accuracy of gastric MALT lymphoma diagnosis. IgHr-positive status at pCR may signal higher recurrence risk, underscoring the need for careful post-CR surveillance. Surveillance should account for potential delays in IgHr-negative conversion.