Cancer Research Articles

Using artificial intelligence to prioritize pathology samples: report of a test drive.

The digital transformation of pathology, through automation and computational tools, addresses current challenges in the field. This study evaluates Paige Pan Cancer, a novel artificial intelligence tool based on the Virchow foundation model, designed to flag invasive cancer in haematoxylin and eosin-stained slides from 16 primary tissue types. Using 62 cases from the Ipatimup Pathology Laboratory, we found the tool had a sensitivity of 93.3% and specificity of 87.5% in biopsies, and 94.7% sensitivity and 75.0% specificity in resections. Overall accuracy was 90.3%. Despite some misclassifications, Paige Pan Cancer demonstrates high sensitivity as a multi-organ screening tool in clinical practice.

The role of N6-methyladenosine modification in tumor angiogenesis

Tumor angiogenesis is a characteristics of malignant cancer progression that facilitates cancer cell growth, diffusion and metastasis, and has an indispensable role in cancer development. N6-methyladenosine (m6A) is among the most prevalent internal modifications in eukaryotic RNAs, and has considerable influence on RNA metabolism, including its transcription, splicing, localization, translation, recognition, and degradation. The m6A modification is generated by m6A methyltransferases (“writers”), removed by m6A demethylases (“erasers”), and recognized by m6A-binding proteins (“readers”). There is accumulating evidence that abnormal m6A modification is involved in the pathogenesis of multiple diseases, including cancers, and promotes cancer occurrence, development, and progression through its considerable impact on oncoprotein expression. Furthermore, increasing studies have demonstrated that m6A modification can influence angiogenesis in cancers through multiple pathways to regulate malignant processes. In this review, we elaborate the role of m6A modification in tumor angiogenesis-related molecules and pathways in detail, providing insights into the interactions between m6A and tumor angiogenesis. Moreover, we describe how targeting m6A modification in combination with anti-angiogenesis drugs is expected to be a promising anti-tumor treatment strategy, with potential value for addressing the challenge of drug resistance.

Effect of Exercise Intervention on Chemotherapy-Induced Peripheral Neuropathy Symptoms in Cancer Patients: A Meta-analysis.

Exercise has been widely used to improve chemotherapy-induced peripheral neuropathy symptoms in cancer patients in recent years; however, there is insufficient evidence to support the effectiveness of exercise intervention in cancer patients. This review aims to comprehensively evaluate the effectiveness of exercise intervention in the management of chemotherapy-induced peripheral neuropathy symptoms in cancer patients and to explore effective exercise intervention characteristics by comparing the effects of different exercise prescriptions. Ten databases were systematically searched from published up to May 2024. The studies that met the inclusion criteria were included. The risk of bias was assessed using the Cochrane Collaboration tool. The statistical analyses were performed in Stata 17.0. A total of 21 studies with 775 participants were included. The pooled results showed that exercise significantly reduced the severity of chemotherapy-induced peripheral neuropathy symptoms; relieved neuropathic pain; enhanced balance function, muscle strength, physical flexibility, and physical endurance; and improved the quality of life of cancer patients with chemotherapy-induced peripheral neuropathy, both compared with patients in the usual care group and with patients' baseline symptoms before exercise. However, no significant improvement in fear of falling was observed. Exercise is an effective way of managing chemotherapy-induced peripheral neuropathy symptoms. The patient's age, exercise cycles, and frequency can affect the effect of the intervention. Oncology nurses can significantly manage chemotherapy-induced peripheral neuropathy symptoms in cancer patients through exercise intervention. Further research is necessary to explore the most suitable characteristics of exercise intervention to achieve optimal intervention effectiveness.

Challenges following CRS and HIPEC surgery in cancer patients with peritoneal metastasis: a comprehensive review of clinical outcomes

Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) are a pair of relatively modern therapeutic surgical methods in advanced cancerous patients with peritoneal metastasis (PM). The goal of CRS + HIPEC is treatment or to improve survival outcomes, which are linked to high morbidity side effects and complications, even with their possible advantages. Surgical-related, chemotherapy-related, anesthetic-related, gastrointestinal, organs and systemic complications are the categories into which complications are separated according to frequency, risk factors, and effect on patient outcomes. In this narrative review of the literature, the side effects and complications of HIPEC + CRS in cancer patients with PM are examined. The present knowledge on the incidence, frequency, kinds, and risk factors of acute complications following CRS + HIPEC is summarized in this study. This review emphasizes the need for careful patient selection criteria, precise surgical technique, and thorough intraoperative care to reduce or manage these risks. Moreover, it highlights the need for interdisciplinary collaboration in treating these patients. This study aims to know these complications, improve clinical practice, and guide future studies to increase the safety and efficacy of CRS + HIPEC in treating metastatic colorectal cancer.

Psychometric properties of Farsi version of Demoralization Scale-II (DS-II) in Iranian cancer patients.

Demoralization, a prevalent form of psychological distress, significantly impacts patient care, particularly in terminally ill individuals, notably those diagnosed with cancer. This study aimed to assess psychometric properties of Farsi version of Demoralization Scale-II (DS-II) in Iranian cancer patients. This study was descriptive-analytical cross-sectional research. The statistical population was cancer patients who sought treatment at Imam Khomeini Hospital in Tehran throughout the 2021-2022. In the initial phase of the study, a preliminary sample comprising 200 patients was carefully selected through convenience sampling. After applying these criteria, 160 patients satisfactorily completed the questionnaires, forming the final study sample. They completed series of questionnaires that included sociodemographic information, DS-II, Scale of Happiness of the Memorial University of Newfoundland, and Beck Depression Inventory (BDI-II). The evaluation included exploratory factor analysis, confirmatory factor analysis (CFA), assessments of convergent validity, and internal consistency reliability. The CFA revealed a 2-factor model consistent with the original structure. The specific fit indices, including the Comparative Fit Index, Root Mean Square Error of Approximation, and Goodness-of-Fit Index, were 0.99, 0.051, and 0.86, respectively. Significant correlation coefficients (p < 0.05) were found between the DS-II and the Beck Depression and MUNSH Happiness scales. The internal consistency of the DS-II, as measured by Cronbach's alpha, yielded values of 0.91 for the meaning and purpose factor, 0.89 for the coping ability factor, and 0.92 for the total score. The Farsi version of DS-II has demonstrated reliability and validity in evaluating demoralization among cancer patients in Iran. This tool can offer valuable insights into the psychological problems of terminally ill patients. Further research opportunities may include conducting longitudinal studies to track demoralization over time and exploring the impact of demoralization on the overall well-being and care of terminally ill patients in Iranian society.

Clinical applications of circulating tumor cell detection: challenges and strategies.

Circulating tumor cells (CTCs) are pivotal in the distant metastasis of tumors, serving as one of the primary materials for liquid biopsy. They hold significant clinical importance in assessing prognosis, predicting efficacy, evaluating therapeutic outcomes, and studying recurrence, metastasis, and resistance mechanisms in cancer patients. Nevertheless, the rareness and heterogeneity of CTC and the complexity of metastasis make the clinical application of CTC detection confront many challenges, which may need to be settled by some practical strategies. This article will review the content mentioned above.

Preoperative fractional exhaled nitric oxide is a risk and predictive factor of postoperative cough for early-stage non-small cell lung cancer patients: a longitudinal study

BackgroundTo determine whether preoperative fractional exhaled nitric oxide (FENO) level is a risk and predictive factor of postoperative cough by using the Leicester Cough Questionnaire in Mandarin-Chinese (LCQ-MC).Methods292 early-stage non-small cell lung cancer (NSCLC) patients without preoperative cough were enrolled. 138 patients (47.2%) developed postoperative cough, univariate and multivariate logistic regression analysis were performed to identify the independent risk factors of postoperative cough. For an exploratory analysis, patients with cough were divided into low and high- FENO [≥ 31 parts per billion (ppb)] groups. The LCQ-CM was used to evaluate changes and recovery trajectory of postoperative cough over time between the two groups for 12 months after surgery.ResultsThe independent factors of postoperative cough included preoperative FENO level [odds ratio (OR) 1.106, 95% confidence interval (CI): 1.076–1.137, p < 0.001] and duration of anesthesia (OR 1.008, 95% CI: 1.002–1.013, p = 0.004). The low-FENO group reported significantly higher LCQ-MC scores at 1 month after surgery and returned to preoperative physical (28 vs. 91 days), psychological (28 vs. 60 days), social (28 vs. 80 days) and total (28 vs. 91 days) scores faster than the high-FENO group (all p < 0.05).ConclusionHigher preoperative FENO level and longer duration of anesthesia were independent risk factors related to postoperative cough. Additionally, patients with high preoperative FENO level had worse cough-related quality of life and slower recovery from postoperative cough.Trial RegistrationThis study was approved by the Chinese Clinical Trial Registry (Clinicaltrials.gov number: ChiCTR1900023419) on 26 May 2019 and the first patient was enrolled after pre-registration.

Advances and challenges in chimeric antigen receptor‐natural killer cell immunotherapy for cancer

Chimeric antigen receptor (CAR)‐natural killer (NK)‐cell therapy has emerged as a promising strategy in the treatment of haematological malignancies and solid cancers. Leveraging the innate immune properties of NK cells, CAR‐NK‐cell therapies offer potential advantages for cell therapy, including safety of use in the allogeneic setting and reduced risk of toxicity. This Nutshell provides an overview of the latest advancements in CAR‐NK‐cell therapy and the challenges that remain.

Fatty acid traits mediate the effects of uric acid on cancers: a Mendelian randomization study

IntroductionPrevious findings on the association between uric acid (UA) levels and cancer risk are conflicting. Moreover, the mechanisms underlying the interactions between UA levels, fatty acid traits, and cancer outcomes remain complex; it is still unclear whether elevated UA levels influence fatty acid traits and, thereby, contribute to an increased cancer risk. Therefore, we aimed to investigate the association between UA levels and cancer risk, with a specific focus on the potential mediating role of fatty acid traits.MethodsWe employed a Mendelian randomization (MR) analysis utilizing genetic data from large-scale genome-wide association studies to assess the causal relationships among UA levels, fatty acid traits, and cancer risk. The primary method used was the inverse variance-weighted approach alongside Bayesian-weighted Mendelian randomization. Other MR models were also applied for comparison. Sensitivity analyses, based on various statistical assumptions, were also performed to evaluate the robustness of the findings. A two-step MR analysis was conducted to explore the mediating effects of fatty acid traits on the relationship between UA levels and cancer risk.Results and Discussion Elevated UA levels were associated with an increased risk of in situ neoplasms, cervical cancer, and invasive mucinous ovarian cancer, while they were linked to a decreased risk of cancers of the eye and adnexa, small cell lung cancer, bronchus and lung cancer, respiratory system and intrathoracic organ cancers, as well as lung cancer. Mediation analysis revealed that fatty acid traits, particularly the docosahexaenoic acid/trans fatty acid ratio, mediated the relationship between UA levels and lung cancer risk. These findings underscore the potential of fatty acid traits to mediate the association between UA levels and cancer risk, offering new insights for targeted interventions and potentially improving clinical outcomes.

The impact of setup errors on dose distribution in cervical cancer radiotherapy and the margin from CTV to PTV

PurposeThis study calculates the needed margin from clinical target volume (CTV) to planning target volume (PTV) in IMRT for cervical cancer. It also assesses the impact of setup errors on target and organ at risk (OAR) dose distribution.MethodsWe retrospectively analyzed 50 cervical cancer patients who underwent IMRT, with 210 CBCT scans. We calculated the CTV-to-PTV margin and simulated setup errors in the TPS to reassess dose distribution impacts on targets and OAR.ResultsSetup errors in X(anterior–posterior,AP), Y(cranial–caudal,CC), and Z(left–right,LR) directions were (1.4 ± 1.0) mm, (2.3 ± 1.5) mm, and (1.9 ± 1.2) mm, respectively, leading to CTV-to-PTV margins of 4.4 mm, 6.4 mm, and 5.8 mm. X-axis errors did not significantly affect target dosimetry (P > 0.05), but Y and Z errors did (P < 0.05). X-axis errors impacted the small intestine and rectum (P < 0.05), Y-axis errors mainly affected the colon (P < 0.05), and Z-axis errors affected the colon, small intestine, and rectum (P < 0.05).ConclusionOur study underscores the need to account for setup errors in radiotherapy for cervical cancer. Customizing the CTV-to-PTV margin based on institutional error data is key to maintaining target dose coverage and optimizing treatment outcomes.

Supportive care needs and associated factors among caregivers of elderly patients with gastrointestinal cancer: an exploratory study

BackgroundGastrointestinal cancers, including gastric and colorectal cancers, are major contributors to cancer-related morbidity and mortality worldwide, placing significant burdens on patients and their informal caregivers. This study aims to evaluate the level of supportive needs among informal caregivers of patients with gastrointestinal cancer and to identify key factors influencing these needs.MethodsWe conducted a descriptive survey involving 335 informal caregivers of patients with gastrointestinal cancer at a large hospital in Shanghai, China, from September 2023 to April 2024. Multivariate linear regression analysis was employed to examine potential factors affecting supportive needs, including demographic information, caregiver burden, and self-efficacy.ResultsThe average supportive needs score among the 335 caregivers was 113.59 ± 52.97. This score was positively correlated with caregiver burden (r = 0.363, P < 0.001), self-efficacy (r = 0.224, P < 0.001), and patients’ Karnofsky Performance Status (KPS) score (r = 0.119, P < 0.05). Multivariate regression analysis revealed that the care experience, duration of caregiving, relationship (sibling), self-efficacy, caregiver burden, KPS score of patients, treatment duration of patients, and cancer type of patients were significant factors influencing the supportive care needs of caregivers for elderly gastrointestinal cancer patients (P < 0.05).ConclusionInformal caregivers of elderly patients with gastrointestinal cancer often have increased levels of supportive needs. Clinical practice should include comprehensive assessments of these needs and the development of targeted interventions to improve caregiving skills and reduce caregiver burden, thereby enhancing the quality of life for both caregivers and patients.

Prognostic effect of immunohistochemically determined molecular subtypes in gastric cancer

IntroductionGastric cancer is the fifth most common cancer worldwide and the fourth most common cause of cancer-related death. Two molecular subtyping classifications were recently introduced: The Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG) classifications.MethodsWe classified a cohort of 283 gastric cancer patients undergoing surgery at Helsinki University Hospital between 2000 and 2009. We constructed a tumour tissue microarray immunostained for the following markers: microsatellite instability (MSI) markers MSH2, MSH6, MLH1, and PMS2; p53; E-cadherin; and EBERISH.ResultsIn the univariate survival analysis for disease-specific survival, the Epstein–Barr virus (EBV) -positive subtype exhibited the worst prognosis with a hazard ratio (HR) of 2.49 (95% confidence interval [CI] 1.19–5.25, p = 0.016) compared with the most benign subtype, chromosomal instability (CIN). Using TCGA’s classification, the genetically stable (GS) and MSI subtypes exhibited a worse survival compared with CIN (HR 1.73 [95% CI 1.15–2.60], p = 0.009 and HR 1.74 [95% CI 1.06–2.84], p = 0.027, respectively). Using the ACRG classification, the p53 aberrant subtype exhibited the best prognosis, whereas wild-type p53, MSI, and the epithelial–mesenchymal transition (EMT) subtypes exhibited poorer prognoses (EMT: HR 1.90 [95% CI 1.30–2.77], p < 0.001) when compared with aberrant p53.ConclusionsImmunohistochemical analysis can identify prognostically different molecular subtypes of gastric cancer. The method is inexpensive and fast, yet reveals significant information for clinical decision-making. However, our study did not find that either molecular subtyping performed better than the other classification. Thus, further development of the most optimal grouping of different molecular subtypes is still needed.

Co-developing a theory of change for a personalised multimodal cancer prehabilitation programme in South Wales

BackgroundEvidence suggests that prehabilitation interventions, which optimise physical and mental health prior to treatment, can improve outcomes for surgical cancer patients and save costs to the health system through faster recovery and fewer complications. However, robust, theory-based evaluations of these programmes are needed. Using a theory of change (ToC) approach can guide evaluation plans by describing how and why a programme is expected to work. Theories of Change have not been developed for cancer prehabilitation programmes in the literature to date. This paper aims to provide an overview of the methodological steps we used to retrospectively construct a ToC for Prehab2Rehab (P2R), a cancer prehabilitation programme being implemented by the Cardiff and Vale University Health Board.MethodsWe used an iterative, participatory approach to develop the ToC. Following a literature review and document analysis, we facilitated a workshop with fourteen stakeholders from across the programme using a ‘backwards mapping’ approach. After the workshop, stakeholders had three additional opportunities to refine and validate a final working version of the ToC.ResultsOur process resulted in the effective and timely development of a ToC. The ToC captures how P2R’s interventions or activities are expected to bring about short, medium and long-term outcomes that, collectively, should result in the overarching desired impacts of the programme, which were improved patient flow and reduced costs to the health system. The process of developing a ToC also enabled us to have a better understanding of the programme and build rapport with key stakeholders.ConclusionsThe ToC has guided the design of an evaluation that covers the complexity of P2R and will generate lessons for policy and clinical practice on supporting surgical cancer patients in Wales and beyond. We recommend that evaluators apply a ToC development process at the outset of evaluations to bring together stakeholders and enhance the utilisation of the findings. This paper details a pragmatic, efficient and replicable process that evaluators could adopt to develop a ToC. Theory-informed evaluations may provide better evidence to develop and refine cancer prehabilitation interventions and other complex public health interventions.

Blood-based tumor mutational burden impacts clinical outcomes of immune checkpoint inhibitor treated breast and prostate cancers

BackgroundBreast and prostate tumors are known to be less responsive to immune checkpoint inhibitors (ICIs). Tissue-based tumor mutation burden (tTMB) has emerged as a predictive biomarker of response to ICIs, including in these “cold tumors”. In clinical practice, when tTMB is not available, blood-based TMB score (bTMB) can be used to consider treatment with ICIs.MethodsThis retrospective, real-world study included a final cohort of metastatic breast and prostate cancer patients treated with an ICI following a liquid biopsy test. Multiple bTMB-High cut-offs were assessed. Clinical, genomic, and outcomes data were collected. We hypothesized that a cut-off of bTMB ≥10 mut/Mb is not a strong predictor of response to ICIs in this setting. The Guardant Health genomic database (GHGD) was then queried (N = 13,992) for associations of bTMB with genomic alterations.ResultsIn the clinical cohort (N = 48), ICI treatment is offered after a median of 3 (1–9) lines of treatment. The median bTMB is 16.4 (10–186) mut/Mb. The median time on ICI and PFS is 2.1 (0–1.7) and 3.1 months (95%CI, 1.6–4.6) respectively; no difference by MSI/MMR status (p = 0.152). Response rate among eligible patients (n = 36) is 16.7%; only N = 1/6 in bTMB <16 mut/Mb. High bMSI is associated with higher bTMB (correlation test, r = 0.66, p = 0.000). In the GHGD, patients with bTMB high have significantly more alterations than bTMB low and TP53, PIK3CA, ATM, ESR1, NF1, BRCA2, ARID1A, and APC were the most frequently altered genes.ConclusionsIn this study, the practice of offering an ICIs based on bTMB was uncommon and did not independently predict ICI benefits in patients with refractory, advanced breast and prostate cancers.

WWP1 targeting PTEN for polyubiquitination to promote bone metastasis of luminal breast cancer

Luminal breast cancer exhibits a high incidence of bone recurrence when metastasizing to distant organs. The mechanisms underlying the organotropism of luminal breast cancer cells remain unclear. In this study, we aimed to determine the role of WWP1 (WW domain-containing E3 ubiquitin protein ligase 1)-PTEN (phosphatase and tensin homolog deleted on chromosome ten) interaction in bone tropism in luminal breast cancer. We observed that WWP1 was overexpressed in luminal breast cancer tissues and associated with poor prognosis in breast cancer patients. In luminal breast cancer cells, WWP1 was found to mediate PTEN ubiquitination, resulting in the functional loss of PTEN. As a result, we demonstrate that WWP1 contributes to bone tropism in luminal breast cancer cells via the polyubiquitination of PTEN. Consequently, WWP1-mediated PTEN polyubiquitination contributed to the early metastasis of luminal breast cancer cells to the bone. Thus, our study provides a mechanistic insight into the bone tropism of luminal breast cancer cells and proposes a potential therapeutic strategy for mitigating cancer metastasis to the bone.

The cardio-oncologic burden of breast cancer: molecular mechanisms and importance of preclinical models.

Breast cancer, the most prevalent cancer affecting women worldwide, poses a significant cardio-oncological burden. Despite advancements in novel therapeutic strategies, anthracyclines, HER2 antagonists, and radiation remain the cornerstones of oncological treatment. However, each carries a risk of cardiotoxicity, though the molecular mechanisms underlying these adverse effects differ. Common mechanisms include DNA damage response, increased reactive oxygen species, and mitochondrial dysfunction, which are key areas of ongoing research for potential cardioprotective strategies. Since these mechanisms are also essential for effective tumor cytotoxicity, we explore tumor-specific effects, particularly in hereditary breast cancer linked to BRCA1 and BRCA2 mutations. These genetic variants impair DNA repair mechanisms, increase the risk of tumorigenesis and possibly for cardiotoxicity from treatments such as anthracyclines and HER2 antagonists. Novel therapies, including immune checkpoint inhibitors, are used in the clinic for triple-negative breast cancer and improve the oncological outcomes of breast cancer patients. This review discusses the molecular mechanisms underlying BRCA dysfunction and the associated pathological pathways. It gives an overview of preclinical models of breast cancer, such as genetically engineered mouse models, syngeneic murine models, humanized mouse models, and various in vitro and ex vivo systems and models to study cardiovascular side effects of breast cancer therapies. Understanding the underlying mechanism of cardiotoxicity and developing cardioprotective strategies in preclinical models are essential for improving treatment outcomes and reducing long-term cardiovascular risks in breast cancer patients.

Improved Osteoporosis Prediction in Breast Cancer Patients Using a Novel Semi-Foundational Model.

Small cohorts of certain disease states are common especially in medical imaging. Despite the growing culture of data sharing, information safety often precludes open sharing of these datasets for creating generalizable machine learning models. To overcome this barrier and maintain proper health information protection, foundational models are rapidly evolving to provide deep learning solutions that have been pretrained on the native feature spaces of the data. Although this has been optimized in Large Language Models (LLMs), there is still a sparsity of foundational models for computer vision tasks. It is in this space that we provide an investigation into pretraining Visual Geometry Group (VGG)-16, Residual Network (ResNet)-50, and Dense Network (DenseNet)-121 on an unrelated dataset of 8500 chest CTs which was subsequently fine-tuned to classify bone mineral density (BMD) in 199 breast cancer patients using the L1 vertebra on CT. These semi-foundational models showed significant improved ternary classification into mild, moderate, and severe demineralization in comparison to ground truth Hounsfield Unit (HU) measurements in trabecular bone with the semi-foundational ResNet50 architecture demonstrating the best relative performance. Specifically, the holdout testing AUC was 0.99 (p-value < 0.05, ANOVA versus no pretraining versus ImageNet transfer learning) and F1-score 0.99 (p-value < 0.05) for the holdout testing set. In this study, the use of a semi-foundational model trained on the native feature space of CT provided improved classification in a completely disparate disease state with different window levels. Future implementation with these models may provide better generalization despite smaller numbers of a disease state to be classified.

Risk Factors for Emergency Room Visit by Head and Neck Cancer Patients: A Longitudinal Cohort Study in the Korean Healthcare System.

Due to the application of multiple treatment modalities, a substantial proportion of patients with head and neck cancer (HNC) experience one or more emergency room (ER) visits or unplanned hospitalizations during or after treatment. We investigated HNC cases that visited ERs after cancer treatment to identify potential risk factors in the context of the Korean healthcare system. This was a single-center cohort study of HNC patients who underwent cancer treatments at OOOO in 2019 (N = 566). The patients were treated with surgery alone (N = 184), surgery plus adjuvant therapy (N = 138), curative non-surgical treatment (radiation or chemo-radiation) (N = 209), or palliative treatments (N = 35). We followed up cases for up to 3 years, who visited the ER after (or during) cancer treatments and analyzed the main reasons and risk factors for ER visits. The rate of ER visits was 8.0% (N = 45) of patients with HNC (no. of ER visits, N = 70, 12.4%, mean = 1.56, range = 1-4), among which treatment-related ER visits made up 4.6%. Common reasons for ER visits were surgical site or wound problems (31.1% per patient, 22.9% per ER visits), and oral intake or feeding problems (22.2% per patient, 31.4% per ER visit). Tumor subsite (17.9% of treatment-related ER visits in hypopharynx cancer), tumor burden (8.6-12.2% in T2-4 and 6.7% in N+ status), and treatment modalities (surgery with adjuvant chemo-radiation, 19.4%) were identified as significant risk factors for ER visits, while patient age and comorbidities were not. The most common causes for ER visits were wound and feeding problems in HNC patients, and tumor factors and treatment modalities were independent risk factors for ER visits. Adequate planning and management to address these problems could help reduce ER visits and costs and improve patient care.

Randomised Controlled Trial Evaluating the Impact of Intravenous Iron (ferric carboxymaltose) Supplementation Among Epithelial Ovarian Cancer Patients with Anemia

Randomised Controlled Trial Evaluating the Impact of Intravenous Iron (ferric carboxymaltose) Supplementation Among Epithelial Ovarian Cancer Patients with Anemia

VIM-AS1, which is regulated by CpG methylation, cooperates with IGF2BP1 to inhibit tumor aggressiveness via EPHA3 degradation in hepatocellular carcinoma.

Early tumor recurrence in hepatocellular carcinoma (HCC) remains a challenging area, as the mechanisms involved are not fully understood. While microvascular invasion is linked to early recurrence, established biomarkers for diagnosis and prognostication are lacking. In this study, our objective was to identify DNA methylation sites that can predict the outcomes of liver cancer patients and elucidate the molecular mechanisms driving HCC aggressiveness. Using DNA methylome data from HCC patient samples from the CGRC and TCGA databases, we pinpointed hypermethylated CpG sites in HCC. Our analysis revealed that cg02746869 acts as a crucial regulatory site for VIM-AS1 (vimentin antisense RNA1), a 1.8 kb long noncoding RNA. RNA sequencing of HCC cells with manipulated VIM-AS1 expression revealed EPHA3 as a pathogenic target of VIM-AS1, which performs an oncogenic function in HCC. Hypermethylation-induced suppression of VIM-AS1 significantly impacted HCC cell dynamics, particularly impairing motility and invasiveness. Mechanistically, reduced VIM-AS1 expression stabilized EPHA3 mRNA by enhancing the binding of IGF2BP1 to EPHA3 mRNA, leading to increased expression of EPHA3 mRNA and the promotion of HCC progression. In vivo experiments further confirmed that the VIM-AS1‒EPHA3 axis controlled tumor growth and the tumor microenvironment in HCC. These findings suggest that the downregulation of VIM-AS1 due to hypermethylation at cg02746869 increased EPHA3 mRNA expression via a m6A-dependent mechanism to increase HCC aggressiveness.