Cancer-related factors can negatively affect nutritional status and impact disease trajectory. Prognostic biomarkers such as bioelectrical impedance-derived phase angle (PhA) may help identify patients at higher risk of adverse outcomes. This study aimed to determine optimal PhA cut-off points associated with short-term mortality across different cancer stages. This multicenter cohort included 1121 adult patients with cancer in Brazil (≥18 y; 51.2% females; mean age 60 ± 13 y; 43.6% colorectal cancer; 34.3% tumor, node, metastasis [TNM] IV). PhA was derived from raw bioelectrical impedance values: resistance (R) and reactance (Xc) from a tetrapolar single-frequency device (50 kHz). The primary outcome was 6-mo mortality. PhA's predictive accuracy was estimated using receiver operating characteristic (ROC) curves, and cut-off points were estimated using the Youden index. Cox regression models examined crude and adjusted associations between PhA and mortality across TNM stages (I-IV). PhA values were significantly lower in non-survivors (mean difference: -1.02° in males; -1.21° in females). ROC analyses demonstrated fair predictive performance, with optimal thresholds of ≤ 5.43° for males (AUROC 0.74) and ≤ 4.22° for females (AUROC 0.77). Across TNM stages, PhA consistently predicted mortality, with highest accuracy in stage IV (AUROC 0.75; criterion ≤ 4.72°). In multivariate Cox models, PhA remained independently associated with 6-mo mortality after adjustment for confounders. Stepwise analyses confirmed these findings across all stages. PhA is an independent predictor of short-term mortality in cancer across all TNM stages. Identified thresholds (consistently < 5.5°) may guide risk stratification and support clinical decision-making, although external validation is required.

The association between neighborhood socioeconomic status and lung cancer incidence and mortality risk: A systematic review and meta-analysis of cohort studies from North America, Europe, and Asia.

Coal operations and cancer in the US: A systematic review.

Territorial inequalities in cancer mortality in Chile, 2002-2022: a rurality-continuum analysis using spatiotemporal Bayesian models.

Internal mammary chain and medial supraclavicular lymph node irradiation in stage I-III breast cancer (EORTC trial 22922/10925): an unplanned subset analysis of 20-year outcomes in patients with node-negative breast cancer.

Skin rash during epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy has been associated with better outcomes in non-small cell lung cancer (NSCLC), but previous studies may have overestimated this association because of immortal time bias. We evaluated the association between EGFR-TKI-associated skin rash and mortality while accounting for rash timing. We identified patients with NSCLC who initiated first-line EGFR-TKIs between August 2018 and December 2024 using a Japanese claims database. EGFR-TKI-associated skin rash was defined using a qualifying diagnosis and rash-related treatment recorded in the same calendar month. We performed time-dependent propensity score sequential matching: each patient who newly developed skin rash was matched on the rash-onset day to patients still at risk who had not yet developed skin rash; follow-up started on the matched day. For comparison, we also performed an analysis that did not account for immortal time bias and landmark analyses. Among 11 830 eligible patients, 560 developed incident skin rash. In the time-dependent propensity score sequential matching analysis, 560 patients with skin rash were matched to 5600 patients without skin rash, and skin rash was associated with lower recorded mortality (HR, 0.621; 95% CI, 0.404-0.953). The estimate was stronger in the analysis not accounting for immortal time bias (HR, 0.410), whereas the association was attenuated in landmark analyses. EGFR-TKI-associated skin rash was associated with lower recorded mortality, but the association was weaker after accounting for immortal time bias. Prior studies may have overestimated this association.

Metastatic dissemination represents the primary cause of mortality in gastric cancer (GC), with multi-organ involvement posing a formidable therapeutic challenge. While organ-specific adaptations are well-studied, the conserved cellular programs that confer metastatic competence within primary tumors before dissemination remain poorly defined. We performed integrated single-cell and spatial transcriptomic profiling on paired primary GC tumors and multi-organ metastases. Computational trajectory inference, regulon analysis, and cell-cell communication networks were employed to delineate metastatic evolution. Functional validation was conducted through in vitro models, including co-culture assays and genetic perturbation. We identified a conserved intra-tumoral trajectory from metastasis-initiating cells (MICs) to metastasis-like cells (MLCs) within primary tumors, which transcriptionally converged with cells from anatomically diverse metastases. This progression was orchestrated by an ETS2-centered regulatory network, whose declining activity governed pre-adaptive remodeling. We further resolved cancer-associated fibroblast (CAF) heterogeneity and discovered that ACTA2 + CAFs sustain MIC identity through a specific ligand-receptor interaction, COL9A1-SDC4. Functional assays confirmed that this axis directly drives the migratory and invasive phenotypes of GC cells. This study reveals that metastatic phenotypes may emerge through transcriptional pre-adaptation within primary gastric tumors, orchestrated by a cell-autonomous ETS2 regulatory network governing trajectory progression and sustained by a specialized ACTA2 + CAF niche that maintains MIC identity via COL9A1-SDC4 signaling. These findings suggest a prevention-focused paradigm, identifying the ETS2 circuit and the COL9A1-SDC4 niche axis as complementary candidate targets for intercepting metastasis at its earliest stage.

Breast cancer is the most prevalent cancer among UK women. Screening aims to detect cancer early, improving treatment options, and survival. However, participation varies across England with lower participation and cancer detection rates in London than other regions. We postulate that demographic factors (age, ethnicity, deprivation, and migration) might explain some regional differences. An ecological analysis of aggregated data compared English regions (April 2007-March 2020). Primary outcomes were breast cancer mortality, coverage rate, and rate of screen-detected invasive cancers. Linear regression analyses compared outcomes between London and other English regions, adjusting for age, ethnicity, deprivation, and migration. Data included 104 observations aggregated from 26 202 645 screenings, of which 11.9% were in London. Coverage was lower in London (67.8%) than other English regions (73.6%-79.8%). London had significantly lower rates of screen-detected invasive cancers (mean= 6.2 per 1000, SD = 0.2) compared to 6 of 7 regions (ranging from 6.3 to 6.9 per 1000) and lower breast cancer mortality rate (mean = 31.7, SD = 0.8) than 4 regions (ranging from 33.4 to 36.1). Differences in coverage were attenuated and non-significant after adjustment for demographic factors. Regional differences in screening participation are associated with demographic factors, but breast cancer outcomes in London are not worse than the rest of England. Targeted interventions to improve screening accessibility for underserved communities could reduce inequalities. We describe challenges associated with combining several sources of information when performing our analyses and further research using individual-level data is recommended to confirm results and explore additional predictors. This national ecological analysis demonstrates that lower breast screening coverage and invasive cancer detection rates in London are associated with demographic factors, particularly ethnicity, deprivation, and migration. Despite poorer participation, breast cancer mortality in London is not worse than in other English regions. The findings emphasize the importance of demographic factors in breast screening outcomes and improved data linkage to address regional inequalities in breast cancer screening and outcomes.

Obesity is a major driver of cancer incidence and mortality through insulin resistance, chronic inflammation, adipokine dysregulation, and hormonal pathways. While metabolic and bariatric surgery (MBS) is known to reduce weight and improve metabolic dysfunction, its impact on incident malignancy compared with structured non-surgical management remains incompletely defined. We conducted a retrospective cohort study using the TriNetX federated electronic health record network. Adults aged ≥ 18 years with BMI ≥ 35kg/m² and no prior malignancy were included. Patients undergoing MBS were compared with individuals receiving structured dietary counseling without prior MBS. Propensity score matching incorporated demographic factors, cardiometabolic comorbidities, liver disease, tobacco and alcohol use, hormone exposure, immunosuppressive therapy, and cancer screening encounters. Primary outcomes were incident obesity-related malignancies. Secondary outcomes included non-obesity-related cancers, solid tumors, and hematologic malignancies. Cox proportional hazards models estimated hazard ratios (HR) with 95% confidence intervals (CI) over 5 years of follow-up. After matching, cohorts were well balanced. Obesity-related malignancies occurred in 1.0% of MBS patients versus 1.2% of diet counseling patients (HR 0.775, 95%CI 0.708, 0.847). Significant reductions were observed for breast, colorectal, endometrial, pancreatic, and liver cancers. Non-obesity-related malignancies occurred in 1.7% versus 1.9% (HR 0.784, 0.732-0.841), with lower lung cancer risk (HR 0.498, 0.377-0.657). Overall solid tumor incidence was 2.2% versus 2.5% (HR 0.801, 0.754, 0.851). Hematologic malignancies occurred in 0.26% versus 0.28% (HR 0.824, 0.689-0.984). In a rigorously matched contemporary cohort, MBS was associated with reduced risk of obesity-related, non-obesity-related, solid, and hematologic malignancies compared with structured dietary counseling.

Joint association of physical activity and tea consumption with all-cause and cause-specific mortality: The Rural Chinese Cohort Study.

Many studies have reported an association between Helicobacter pylori infection and an increased risk of colorectal cancer (CRC); however, the impact of eradication therapy on CRC remains unclear. We compared CRC incidence and mortality in individuals who received H. pylori treatment with those in the general population. We conducted a population-based study of 931 585 participants aged ≥ 20 years who received H. pylori eradication (HPE) therapy between 2009 and 2011. We used the one-sample log-rank test to compare standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) for CRC. The mean follow-up period was 12.4 ± 1.1 years. CRC incidence and mortality rates were significantly lower in H. pylori-treated individuals than in the general population (total SIR: 0.66, 95% confidence intervals [CI] 0.64-0.67 and SMR: 0.51, 95% CI 0.49-0.54). Significant results were also observed in the 30-39, 40-49, 50-59, 60-69, and ≥ 70 age groups: The SIRs (95% CIs) were 0.80 (0.71-0.89), 0.73 (0.70-0.77), 0.62 (0.60-0.65), 0.66 (0.63-0.68), and 0.62 (0.59-0.66), respectively, and the SMRs (95% CIs) were 0.53 (0.36-0.76), 0.46 (0.39-0.54), 0.41 (0.37-0.46), 0.48 (0.44-0.53), and 0.65 (0.60-0.71), respectively. Similar results were observed when colon and rectal cancer were analyzed separately. HPE may help reduce the risk and improve the survival from CRC. Its benefits may extend beyond preventing gastric cancer to CRC prevention. Our findings support the need for aggressive H. pylori screening and eradication treatment.

Lung cancer remains the leading cause of cancer mortality, yet blood-based biomarkers are not routinely used in diagnosis. This study evaluated four commercial blood protein assays, originally validated for other indications, in indeterminate pulmonary nodules (IPN). Using a prospective specimen collection, retrospective blinded evaluation design, samples were collected from patients with screening-detected, incidental, or symptomatic IPNs. Cytokeratin 19 fragment (CYFRA 21-1), carcinoembryonic antigen (CEA), cancer antigen 125 (CA-125), and human epididymis protein 4 (HE-4) concentrations were quantified on commercial immunoassays. Logistic regression models were developed using internal training (Train), external testing (Test), and combined reestimation (Train + Test) cohorts and externally validated in an outcome-blinded multicenter cohort (Lung Team Project-2, LTP-2). This study included 816 patients: 371 in Train, 166 in Test, and 279 in LTP-2. Malignancy rates were 54%, 44%, and 64%, respectively. In Train + Test, the area under the receiver operating curve (AUC) for lung cancer was 0.60 (95% confidence interval, 0.56-0.65) for CYFRA 21-1, 0.62 (0.58-0.67) for CEA, 0.60 (0.55-0.65) for CA-125, and 0.65 (0.60-0.70) for HE-4. In LTP-2, AUCs were 0.63 (0.56-0.70), 0.64 (0.57-0.70), 0.48 (0.40-0.55), and 0.61 (0.54-0.68), respectively. Combining all four biomarkers yielded an AUC of 0.70 (0.65-0.74) in Train + Test and 0.61 (0.54-0.68) in LTP-2. In the first biomarker study reporting external validation in LTP-2, CYFRA 21-1, CEA, CA-125, and HE-4 demonstrated diagnostic value in IPNs. By leveraging commercial assays, this study highlights opportunities to enhance lung cancer risk stratification using widely available diagnostics that could be rapidly integrated into clinical workflows.

Liver disease remains a leading cause of global cancer mortality and predominantly originates from chronic liver cirrhosis. Current surveillance strategies often suffer from suboptimal sensitivity which necessitates the discovery of robust biomarkers for early detection. In this study we utilized blood resources from the National Biobank of Korea to evaluate the diagnostic potential of Nuclear Magnetic Resonance spectroscopy-based metabolomics in patients with cirrhosis and liver cancer. We aimed to identify specific biomarkers and investigate their correlation with clinical blood parameters by comparing the metabolic profiles of disease and healthy control groups. Multivariate statistical analysis demonstrated significant metabolic distinctions between liver disease patients and healthy controls. While the models successfully differentiated disease states the global metabolic landscape exhibited an overlap between cirrhosis and cancer groups suggesting a shared pathological background driven by systemic metabolic shifts. Quantitative assessment identified specific metabolic alterations characterizing the disease progression. We observed a marked accumulation of lactate and phenylalanine reflecting the Warburg effect and impaired hepatic hydroxylation capacity. Conversely branched chain amino acids specifically valine and isoleucine were significantly depleted in the disease groups indicating systemic metabolic stress. Receiver operating characteristic analysis revealed that a combinatorial biomarker panel yielded superior diagnostic accuracy compared to single markers. Furthermore, the validity of our metabolic profiling was corroborated by a strong correlation between the values predicted from metabolic profiles and clinically measured physiological parameters. Overall, our findings confirm the feasibility of utilizing retrospective biobank resources for high resolution metabolic phenotyping.

In the US, breast cancer mortality is lower among Asian American females diagnosed with breast cancer compared with other racial and ethnic groups, although reasons for this difference are not well understood. To examine contributions of clinical, lifestyle, and sociodemographic factors to mortality differences among females identifying as Asian races and ethnicities compared with non-Latina White females and whether associations vary by nativity. This cohort study analyzed time-to-event survival data from Asian and White females with breast cancer from 4 epidemiologic studies. Cohorts were recruited from California and Hawaii, with information from questionnaires and cancer registries. Participants were females with first primary invasive breast cancer diagnosed from 1992 to 2019 who self-identified as Asian and females who self-identified as White as a comparison group. Analyses were conducted from February 2024 to February 2026. Self-reported race and ethnicity, nativity, clinical factors (eg, stage and tumor grade), marital status, educational level, reproductive factors, insurance status, lifestyle factors (eg, smoking and alcohol use), diabetes, and neighborhood socioeconomic indicators. The outcomes of interest were all-cause and breast cancer-specific mortality. Cox proportional hazards models were used to estimate hazard ratios (HRs) comparing each Asian group with White females, and changes in these estimates with adjustment for various prognostic factors. A total of 8994 females (mean [SD] age at diagnosis, 59 [13] years), including 3973 Asian females and 5021 White females, were analyzed. There were 2637 total deaths and 1140 deaths attributed to breast cancer (mean follow-up time 12.6 years; range, 1 month to 28 years). Most Asian groups had a higher proportion diagnosed before age 50 years compared with White females: from 34% among Filipinas to 73% among another Asian group vs 15% among White females. Nearly all Asian ethnic groups had lower proportions (45%-67%) of localized stage disease relative to White females (69%). Relative to White females, risk of all-cause mortality in fully adjusted models was lower for Chinese females (HR, 0.77; 95% CI, 0.62-0.96), Filipina females (HR, 0.81; 95% CI, 0.67-0.99), Japanese females (HR, 0.71; 95% CI, 0.54-0.93), and Asian females identifying as multiple races or ethnicities, not Native Hawaiian or Pacific Islander (HR, 0.67; 95% CI, 0.51-0.89). Lower adjusted risk of all-cause mortality was observed for Chinese (HR, 0.73; 95% CI, 0.57-0.94) and Filipina (HR, 0.79; 95% CI, 0.63-0.94) females born outside the US and Japanese females (HR, 0.63; 95% CI, 0.45-0.90) and Asian females with multiple races or ethnicities, not Native Hawaiian or Pacific Islander (HR, 0.59; 95% CI, 0.39-0.88) born in the US compared with White females. In this pooled cohort study of females with breast cancer, several Asian groups had lower risk of all-cause mortality, even after accounting for clinical, sociodemographic, reproductive, lifestyle, and neighborhood factors. Identification of the specific resiliency factors will provide insights into mechanisms that may improve survival after breast cancer.

Colorectal carcinoma (CRC) remains a leading cause of cancer mortality, largely due to metastasis. Solid tumors, including CRC, must adapt to intratumoral hypoxia and oxidative stress, but the tumor-cell programs that couple these pressures to metastatic competence remain unclear. Across human CRC cohorts and cell lines, HIF-1α was coordinately upregulated and co-expressed with the metabolic effectors GLUT3 and fatty-acid synthase (FASN), most prominently in metastatic lesions. Using HIF-1α (HRE), SREBP1 (SRE), and NRF2 (ARE) transcriptional reporters, we identified HRE-high and SRE-high CRC subpopulations with enhanced clonogenicity and invasion that drove accelerated tumor growth and increased lung metastatic burden across multiple CRC models. Mechanistically, IGF1 and insulin signaling through IGF1R and AKT-mTOR increased HIF-1α and induced FASN and GLUT3, enabling lipogenic, glycolytic, and antioxidant programs to withstand hypoxic and oxidative stress. HIF-1α engaged an HRE-containing proximal region of the human FASN promoter independently of SREBP1. Stress assays revealed functional specialization: FASN promoted NRF2-associated antioxidant capacity and resistance to oxidative injury, whereas GLUT3 preferentially supported hypoxia tolerance. In vivo, lipid nanoparticle-encapsulated echinomycin rapidly suppressed HRE, SRE, and ARE activity, reduced peri-hypoxic induction of FASN and GLUT3, inhibited tumor growth, and eliminated lung metastasis. These findings define a growth factor-responsive, HIF-1α-centered stress-adaptive state and highlight HIF-1α transcriptional activity as a therapeutic target in metastatic CRC.

Multi-scale evidence chain: Linking environmental BPA exposure to ovarian cancer through integrated omics and experimental models.

Computational and experimental elucidation of ginsenoside Rh2 as a FAK-targeted inhibitor of tumor cell invasion and migration.

Benefits and harms of lung cancer screening strategies in Argentina: a modeling study.

Non-small cell lung cancer (NSCLC) remains a leading cause of cancer mortality, and many patients derive limited benefit from current systemic therapies. Until now, clinical and translational efforts have largely focused on recurrent genomic alterations in the Kelch-like ECH-associated protein 1-nuclear factor erythroid 2-related factor 2 (NRF2) axis, yet mutation status alone often fails to capture the biological heterogeneity and context dependence of NRF2 pathway dysregulation. In recent years, growing evidence has highlighted the NRF2 activation state as a clinically relevant feature that better reflects resistance phenotypes and therapeutic liabilities than genotyping alone. The recent work by Härkönen et al, published in The Journal of Pathology, suggests that anchoring genotype to phenotype using functional readouts is essential for defining NRF2 hyperactivity. Mechanistic studies further suggest that NRF2 hyperactivity can impose context-dependent metabolic liabilities. We discuss the next steps towards clinical translation, including prospective NRF2 activation-state stratification, integration of immune context for immunotherapy, and biomarker evaluation of redox and metabolic combinations based on NRF2-associated vulnerabilities. © 2026 The Pathological Society of Great Britain and Ireland.

Uptake of breast cancer screening varies between English regions despite adherence to similar screening protocols across regions and screening services. Poor uptake is thought to impair breast cancer outcomes, including the assumption of higher breast cancer mortality. There are known demographic differences between English regions, and there has been limited investigation into which characteristics are associated with behavior and outcomes in a single region compared with overall national performance. In this research letter, we outline the challenges we have faced when conducting this analysis using routinely collected data and provide recommendations to facilitate similar work in the future.