The incidence and mortality of colorectal carcinoma (CRC) continue to rise globally, highlighting the need to identify modifiable risk factors for early detection and prevention. Previous studies have demonstrated significant associations between CRC risk and various serum metabolites as well as inflammatory cytokines; however, due to limitations in study design and potential confounding factors, the causal relationships remain unclear. This study aims to investigate the causal relationships between inflammatory cytokines, serum metabolites, and CRC risk, providing a theoretical basis for the development of novel early diagnostic biomarkers and therapeutic targets.

A two-sample Mendelian randomization (MR) design was applied using summary statistics from genome-wide association studies (GWAS). Instrumental variables (IVs) were derived from: 1) metabolomics GWAS data of 1 400 serum metabolites (n=8 299); 2) cytokine GWAS data of 91 inflammatory factors (n=14 824); and 3) CRC risk data from the FinnGen consortium (6 847 cases and 314 193 controls). The primary analysis was conducted using the inverse-variance weighted (IVW) method, with sensitivity analyses performed using MR Egger regression and the weighted median method. Effect estimates including odds ratios (OR), 95% confidence intervals (CI), and false discovery rates (FDR) were calculated.

MR analysis indicated that higher levels of axin-1 (AXIN1) (OR=0.841 95% CI 0.714 to 0.991) and Fms-related tyrosine kinase 3 ligand (Flt3L) (OR=0.916, 95% CI 0.844 to 0.994) were associated with a reduced risk of CRC. In contrast, higher levels of Delta/Notch- like epidermal growth factor-related receptor (DNER) (OR=1.119, 95% CI 1.009 to 1.241) and vascular endothelial growth factor A (VEGF-A) (OR=1.078, 95% CI 1.011 to 1.150) were associated with an increased risk of CRC (all P<0.05). Metabolomics association analysis further identified 144 serum metabolites significantly correlated with these four key inflammatory cytokines (FDR<0.05), suggesting that they may regulate CRC risk through inflammatory pathways.

Specific inflammatory cytokines and serum metabolites have causal relationships with the risk of CRC. These findings provide insights for further exploration of potential risk factors and the development of effective prevention strategies for CRC.

Patients with advanced epidermal growth factor receptor (EGFR)-mutated adenocarcinoma often receive frontline first- and second-generation EGFR tyrosine kinase inhibitor (TKI) treatments in Taiwan. However, upon progression, not all patients undergo rebiopsy for molecular testing. In some cases, tumors are located in difficult-to-access areas, and some rebiopsy specimens are inadequate for pathological and molecular assessment. Our aim is to evaluate the efficacy of the third-generation EGFR TKI, osimertinib, in tumors with unknown T790M mutation status.

This study retrospectively collected data from patients with EGFR-mutant advanced lung adenocarcinoma who received first-line first- or second-generation EGFR TKI therapy followed by the third-generation EGFR TKI osimertinib without rebiopsy to assess T790M mutation status between January 2015 and December 2024. Efficacy and survival outcomes are presented.

A total of 160 patients with EGFR-mutated lung adenocarcinoma at clinical stages IIIB-IVB received first- or second-generation EGFR-TKI frontline therapy. After disease progression, 82 patients were treated with osimertinib as a second-line therapy with unknown T790M mutation status. Among them, 48 patients initially received afatinib as frontline treatment, while 34 patients received erlotinib. The best tumor response rate (RR) was 42.7%, with a median time on treatment (ToT) of 5.6 months (95% CI, 4.0-9.3). Swim-plot visualization highlighted a hierarchical pattern wherein longer first-line duration frequently co-occurred with longer empirical second-line duration.

Osimertinib treatment is a viable option for patients who progress on frontline first- or second-generation EGFR TKI therapy without rebiopsy and have an unknown T790M mutation status. The RR of 42.7% and median ToT of 5.6 months appear consistent with historical outcomes reported for second-line platinum-based chemotherapy. Osimertinib provides an additional treatment line for patients whose tumors are difficult to access and have an unknown T790M status, making it a valuable treatment option for these patients.

High mammographic density is a well-known risk factor for breast cancer and reduces the sensitivity of mammography-based screening. While automated machine and deep learning-based methods provide more consistent and precise measurements compared to subjective Breast Imaging Reporting and Data System (BI-RADS) assessments, they often fail to account for the longitudinal evolution of density. Many of these methods assess mammographic density in a cross-sectional manner, overlooking correlations in repeated measures, irregular visit intervals, missing data, and informative dropouts. Joint models address these limitations by simultaneously modeling the relationship between longitudinal biomarkers and time-to-event outcomes. We introduce the DeepJoint algorithm, an open-source method combining deep learning-based mammographic density estimation with joint modeling to assess its longitudinal relationship with breast cancer risk. Our approach adequately analyzes processed mammograms from various manufacturers, estimating both dense area and percent density, two established risk factors for breast cancer. We utilize a joint model to explore their association with breast cancer risk and provide individualized risk predictions. Bayesian inference and the consensus Monte Carlo algorithm make the approach reliable for large screening datasets. By integrating deep learning with joint modeling, our new method provides a robust, comprehensive framework for evaluating breast cancer risk based on longitudinal density profiles. The complete pipeline is publicly available, promoting broader application and comparison with other methods.

Liquid biopsy offers a minimally invasive approach to early cancer diagnosis. MicroRNAs (miRNAs) are small, non-coding RNAs showing excellent diagnostic potential due to their stability and dysregulation upon different physiological conditions. However, existing miRNA-based cancer classifiers rely on cohort-based comparisons, limiting their clinical utility. Extensive analyses in this study present miRNA binary trend (miRBiT), a miRNA rules-based single-sample classifier, trained on 16,190 samples, tested across nine independent datasets, and further validated on 8 distinct disease cohorts. miRBiT utilizes miRNA expression signatures at an intra-sample level to classify 'cancer' and 'non_cancer' samples, including healthy and other diseases with high sensitivity and specificity, enabling personalized predictions. Additionally, an interactive web application, miRBiT Explorer serum miRNA expression resource, is developed to visualize and validate serum miRNA expression patterns in 46,349 samples. This study highlights the potential of miRNAs in robust cancer classification, enabling personalized, minimally invasive cancer screening and early detection at an unprecedented scale.

IntroductionAustralia has one of the highest incidence rates of multiple myeloma (MM) globally, and this burden is projected to increase significantly in the coming decades. Survival has improved over time, but it is not clear how this differs by socioeconomic group. Here, we used population-based data to evaluate survival differences by socioeconomic group and other prognostic factors of individuals with MM in Australia.MethodsThis retrospective study included individuals diagnosed with primary MM between 2008 and 2019, as recorded in the New South Wales Cancer Registry, with survival follow-up to 2020. The identified individuals with primary MM were classified into 3 socioeconomic groups (low, medium, high) based on their residential location at diagnosis. Competing-risk modelling was used to estimate sub-hazard ratios (SHR) for socioeconomic group adjusting for potential prognostic factors, including age at diagnosis, sex, year of diagnosis, remoteness areas, autologous stem cell transplantation (ASCT) use, and hospital type.ResultsOverall, 6,030 individuals were included in the study. The 5-year cumulative incidence of death due to MM was higher (p<0.0001) in low and medium socioeconomic groups (0.42 and 0.39), compared with the high socioeconomic group (0.34). Individuals in the high socioeconomic group were more likely to receive ASCT and to receive care at public principal referral/private hospitals. Compared to the high socioeconomic group, the excess risk of dying was higher (p<0.0001) in low (SHR=1.27, 95% CI: 1.14-1.42) and medium (SHR=1.20, 95% CI: 1.08-1.33) socioeconomic groups, but not statistically different (p=0.13) when other prognostic factors were considered.ConclusionSurvival disparity by socioeconomic groups among individuals with MM in Australia is largely accounted for by known prognostic factors, especially ASCT receipt and hospital type. Existing disparities suggest that a comprehensive evaluation of access to and availability of MM treatment, including identification of potential barriers to treatment receipt, is urgently needed.

Cordyceps militaris, a traditional medicinal fungus and a promising food supplement, has demonstrated anticancer potential, yet its underlying mechanisms and in vivo efficacy remain poorly defined. Previously, we developed an optimized extraction and preparation protocol to enrich the bioactive content of C. militaris, specifically adenosine and cordycepin. Here, using this optimized C. militaris extract (CME), we investigated its antitumor effects and underlying mechanisms in a murine lung cancer model. Components of CME were quantified using high-performance liquid chromatography. In vivo, CME significantly suppressed tumor growth in LLC1-bearing mice. Mechanistically, CME induced ferroptosis, an iron-dependent form of regulated cell death characterized by lipid peroxidation and redox imbalance. Tumors from CME-treated mice displayed elevated lipid ROS, increased iron accumulation, glutathione depletion, and downregulation of glutathione peroxidase 4. Apoptotic signaling was accompanied with ferroptosis, but neither pyroptosis nor necroptosis contributed to CME-induced lung cancer death. Pharmacological rescue experiments confirmed the specificity of ferroptosis as the dominant mode of cell death. Importantly, CME caused no systemic toxicity, and its approximate lethal dose was over 5000 mg/kg. Together, these findings suggest CME as a potent ferroptosis-inducing agent against lung cancer and establish C. militaris as a promising candidate for redox-targeted cancer therapy.

Adherence to subsequent lung cancer screening (LCS) is essential but not well characterized in biennial national programs.

To assess whether baseline LCS results and their management are associated with subsequent screening adherence and clinical outcomes.

We analyzed participants in the Korean national LCS program who underwent baseline low-dose computed tomography (CT) between 2019 and 2021 and remained lung cancer-free for 2 years. Baseline results were classified as true negative or false positive (FP); FPs were grouped by management (invasive diagnostic procedures, chest CT surveillance, or no further evaluation). Adherence to the next biennial screening was modeled using multivariable logistic regression. Lung cancer incidence and all-cause mortality were assessed using Cox models with a 2-year landmark design.

Among 235,753 participants, 54.4% returned for subsequent screening. Compared with true-negative results, adherence was lower among those with FP results who underwent invasive procedures (adjusted odds ratio [aOR], 0.64; 95% confidence interval [CI], 0.56-0.72) or CT surveillance (aOR, 0.77; 95% CI, 0.74-0.80) but was similar among those with FP results without further evaluation (aOR, 1.00; 95% CI, 0.95-1.04). In the landmark analysis, FPs were associated with higher risks of lung cancer incidence (adjusted hazard ratios [aHRs], 2.95-2.49 across management groups) and higher all-cause mortality among those who underwent invasive procedures (aHR, 1.57; 95% CI, 1.10-2.24) or CT surveillance (aHR, 1.23; 95% CI, 1.07-1.41).

Downstream management after baseline FP findings, rather than FP status alone, was associated with subsequent LCS adherence, highlighting the need to support return screening in higher risk FP groups.

Blood cancers, including leukemia, lymphoma, and myeloma, are complex malignancies influenced by genetic, environmental, and epigenetic factors. Among these, epigenetic modifications play a crucial role in cancer initiation and progression. This review explores the interplay between dietary patterns, epigenetic mechanisms, and blood cancer development, highlighting the potential of diet-based interventions in cancer prevention and therapy. A growing body of evidence suggests that dietary habits significantly impact epigenetic modifications such as DNA methylation and histone modifications, which regulate gene expression. Phytochemicals, including curcumin, resveratrol, quercetin, and epigallocatechin gallate (EGCG), exhibit promising epigenetic modulation in blood cancer. These compounds influence DNA methyltransferases (DNMTs) and histone deacetylases (HDACs), restoring normal epigenetic patterns and reactivating silenced tumor suppressor genes (TSGs). Individual variability in dietary response, bioavailability of bioactive compounds, and the complexity of epigenetic interactions necessitate further research in nutri-epigenomics. Future directions should focus on personalized nutrition strategies and clinical trials to validate the efficacy of dietary approaches in blood cancer prevention and therapy. In conclusion, diet plays a pivotal role in epigenetic regulation, influencing the risk and progression of blood cancer. Understanding the molecular mechanisms underlying dietary epigenetic modifications may open new avenues for preventive and therapeutic strategies.

Ileal conduit diversion is currently the most commonly used urinary diversion method for patients undergoing radical cystectomy. Because intestinal reconstruction is involved, perioperative enteral nutrition intake is limited, placing patients at risk of malnutrition and affecting postoperative recovery and quality of life. Whole-process perioperative nutritional management is of great significance for promoting rapid postoperative recovery in such patients. This study aims to explore the effects of whole-process nutritional management intervention based on the information-knowledge-attitude-practice (IKAP) theory on nutritional status and quality of life in patients undergoing radical cystectomy for bladder cancer.

A total of 69 patients who underwent radical cystectomy with ileal conduit diversion for bladder cancer in the Department of Urology, Third Xiangya Hospital of Central South University, between January 2022 and December 2024 were included. Patients were grouped according to admission time. Patients admitted between January 2022 and October 2023 were assigned to the control group (n=34) and received routine perioperative nutritional support for radical cystectomy with ileal conduit diversion. Patients admitted between November 2023 and December 2024 were assigned to the intervention group (n=35) and received whole-process nutritional management based on IKAP theory. Nutritional Risk Screening 2002 (NRS2002) score, Onodera's prognostic nutritional index (OPNI), and the third edition Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTCQLQ-C30) were compared between the 2 groups at 3 time points: day 1 after admission, 1 day before discharge, and 1 month after discharge. The incidence of postoperative related complications between the two groups was also compared.

In both groups, the NRS2002 score at 1 month after discharge was lower than that at 1 day before discharge, and the intervention group had lower scores than the control group, with statistically significant differences (all P<0.05). The OPNI at 1 month after discharge was significantly higher than that at 1 day before discharge in both groups, and the intervention group had higher values than the control group, with statistically significant differences (all P<0.05). There was no statistically significant difference in the incidence of postoperative related complications between the 2 groups (all P>0.05). The EORTCQLQ-C30 scores in the intervention group were higher than those in the control group at 1 day before discharge and 1 month after discharge, with statistical significant differences (both P<0.05).

Whole-process nutritional management based on IKAP theory can improve the nutritional status and prognosis of patients undergoing radical cystectomy with ileal conduit diversion and improve their quality of life.

The gut microbiota, as the "second genome" of the human body, plays a crucial role in maintaining the host's homeostasis and regulating the disease process. The latest research indicates that intestinal microecological imbalance is an important cause that triggers and accelerates tumor metastasis. The gut microbiota mainly promotes tumor invasion and metastasis through the following 2 mechanisms: 1) Contact-dependent mechanism, specific pathogenic bacteria directly adhere and invade tumor cells through surface proteins, inducing epithelial-mesenchymal transition and cytoskeleton remodeling; 2) non-contact-dependent mechanism, metabolites derived from the microbiota act on distant organs through the bloodstream, activating signaling pathways to construct pre-metastatic ecological niches and inducing systemic immunosuppression. Precise intervention strategies for the gut microbiota include supplementing specific probiotics with anti-cancer potential, selective antibiotics or phage therapy against specific pathogenic bacteria, fecal microbiota transplantation and microbial vaccines. Although preliminary studies have shown promising results, the high heterogeneity of the microbiota, the bidirectional action of metabolites, and the safety of long-term colonization remain bottlenecks for clinical translation. In the future, it is necessary to further clarify the key transfer-promoting microbiota and their characteristic metabolic and signaling mechanisms, promote the development of individualized and precise microbiota intervention strategies, and strengthen clinical translation research, in order to ultimately achieve the goal of effectively preventing and treating tumor metastasis by regulating the gut microbiota.