[This retracts the article DOI: 10.2147/CMAR.S176525.].

ObjectiveTo evaluate the clinical significance of solute carrier family 2 member 3 (SLC2A3) expression in predicting liver metastasis, postoperative recurrence, and other postoperative complications in patients with colorectal cancer (CRC).MethodsThis was a retrospective cohort study including 150 patients with CRC who underwent surgical treatment. Bioinformatics analyses were conducted to identify differentially expressed genes associated with CRC liver metastasis, from which SLC2A3 was identified as a key candidate. SLC2A3 mRNA expression in tumor and adjacent normal tissues was quantified using quantitative real-time PCR. Patients were stratified according to liver metastasis, postoperative recurrence, and postoperative complications. Multivariable logistic regression models were applied to evaluate independent associations between SLC2A3 expression and postoperative outcomes.ResultsSLC2A3 mRNA expression was significantly upregulated in CRC tumor tissues compared with adjacent normal tissues (P < 0.001). Elevated SLC2A3 expression was associated with liver metastasis, postoperative recurrence, and postoperative complications. In multivariable logistic regression analyses, SLC2A3 expression remained independently associated with postoperative recurrence and complications, while its association with liver metastasis was attenuated after adjustment for tumor differentiation.ConclusionSLC2A3 expression is closely associated with adverse postoperative outcomes in CRC. While its association with liver metastasis appears partly mediated by tumor differentiation, SLC2A3 demonstrates potential as an independent marker, highlighting its potential value in postoperative risk stratification and prognostic assessment. However, these findings should be interpreted with caution due to the retrospective design and lack of external validation.

Oral squamous cell carcinoma (OSCC) with oral submucous fibrosis (OSF) represents a distinct clinicopathological entity with unique prognostic factors not captured by conventional TNM staging. We aimed to develop a fibrosis-integrated nomogram (FIN) for individualized survival prediction in this population. We conducted a retrospective cohort study of 314 consecutive OSCC patients with coexisting OSF treated between 2015 and 2022. Patients were randomly divided into training (n=220) and validation (n=94) sets. Independent prognostic factors were identified using Cox regression and integrated into a nomogram predicting 1-year, 3-year, and 5-year overall survival (OS). Model performance was assessed using C-index, time-dependent ROC curves, calibration plots, and decision curve analysis. Six independent prognostic factors were identified: maximum mouth opening (HR 0.92, P<0.001), areca nut chewing duration >20 years (HR 1.78, P=0.002), N2-3 category (HR 1.89, P=0.001), poor differentiation (HR 1.56, P=0.018), perineural invasion (HR 1.67, P=0.007), and positive surgical margin (HR 2.03, P=0.001). The FIN demonstrated excellent discrimination, with C-indices of 0.79 (95% CI 0.75-0.83) in the training set and 0.77 (95% CI 0.72-0.82) in the validation set, significantly outperforming TNM staging (C-indices 0.68 and 0.66, respectively; both P<0.01). Risk stratification identified three prognostic groups with 5-year OS rates of 78.6%, 48.3%, and 18.9% (log-rank P<0.001). The fibrosis-integrated nomogram significantly improves survival prediction for OSCC patients with OSF by incorporating simple clinical measures of fibrosis severity and carcinogen exposure, enabling individualized risk assessment.

IntroductionCancer care frequently relies on unpaid family caregivers who face substantial psychological strain that may diminish their quality of life (QoL). Local evidence from Kuwait is limited. In Kuwait, where family-based caregiving is culturally normative, the “hidden workload” of caregiving may be substantial yet under-recognized within routine cancer services.ObjectiveTo estimate the prevalence of mental health symptoms including stress, anxiety, and depression among cancer caregivers in Kuwait; to assess caregivers’ health-related QoL; and to identify mental health symptoms predictors.MethodsWe conducted a cross-sectional survey of unpaid family adult caregivers (n=201) of in- and out-patients receiving treatment at major cancer centers in Kuwait. Participants completed a demographics form, the 21-item Depression, Anxiety and Stress Scale (DASS-21), and the SF-36 Health Survey. Descriptive statistics summarized caregiver and patient characteristics. Multiple linear regression analyses were conducted to identify predictors of depression, anxiety, and stress among caregivers.ResultsCaregivers were predominantly female (70.6%) and Kuwaiti (78.1%); most supported non-hospitalized patients. Mental health symptoms mean scores measured by DASS-21 were 6 (±3.8) for depression, 5.6 (±4) for anxiety, and 7 (±4.1) for stress, prevalence of mental health symptoms was 61.2% for depression, 44.8% for stress, and 67.2 for anxiety. SF-36 Physical Composite Score (PCS) mean score was 59.2 (±19.4) and Mental Composite Score (MCS) was 52.5 (±20.4). Mental health symptoms were significantly predicted by SF-36 physical and mental composite scores, educational level, duration of caregiving, living with the patient, and type of help received.ConclusionAbout half of cancer caregivers in Kuwait reported depressive symptoms and nearly one in two reported anxiety, with marked role limitations in daily and emotional functioning. Emotional distress was inversely related to health-related QoL. The findings suggest potential implications for caregiver screening and culturally sensitive psychosocial and rehabilitative supports, including occupational therapy to safeguard caregiver well-being and, by extension, the quality of cancer care. Longitudinal studies could explore trajectories of caregiver mental health and evaluate targeted interventions in the Kuwaiti context.

BackgroundIsolated supraclavicular nodal recurrence (ISNR) is a rare form of recurrence and is regarded as a precursor of a poor prognosis. The surgical removal of ISNR is typically neglected in multimodal therapy.Patients and MethodsAmong 5279 consecutive patients who underwent primary breast cancer surgery at a single hospital between 1977 and 2011, INSR was observed in 77 patients (1.5%). Two INSR patients whose fate was unknown were excluded from the present analysis. Therefore, 75 patients with ISNR treated with (n=58) or without (n=17) neck lymph node dissection (NLND) were evaluated.ResultsOverall survival rates were significantly higher in the NLND group than in the no-NLND group (p = 0.0027). Five- and 10-year survival rates were 64.8 and 47.2%, respectively, in the NLND group and 35.3 and 11.7%, respectively, in the no-NLND group. In a Cox proportional hazards regression (stepwise selection) analysis in which the time interval from the primary surgery to ISNR was excluded, the T factor (T2, 3 vs. T1, hazard ratio 2.26) and NLND (yes vs. no, hazard ratio 0.41) were identified as significant factors affecting OS rates. When the time interval from primary surgery to ISNR was included, the interval from the primary surgery to ISNR (>2 years) and NLND were identified as significant factors for long OS (HR 0.21, HR 0.39).ConclusionISNR is type of a loco-regional recurrence, and NLND needs to be considered in multimodal (radiation and systemic chemo-) therapy.

BackgroundCirculating tumor cells (CTCs) and peripheral T-cell immune checkpoints offer minimally invasive biomarkers for immune checkpoint inhibitor (ICI) therapy. We assessed whether a dual biomarker combining PD-L1 on CTCs and PD-1 on circulating CD8+ T cells is associated with outcomes in advanced non–small cell lung cancer (NSCLC).MethodsWe retrospectively enrolled stage IIIB–IV NSCLC patients treated with anti-PD-1/PD-L1 agents (any line) from January 2022 to December 2023. Eligibility required pretreatment blood and evaluable dual-biomarker testing; all 126 included patients had successful CTC assessment and flow-cytometric CD8+ T-cell PD-1 measurement. Patients were classified as CTC PD-L1–positive if ≥1 CTC showed membranous and/or cytoplasmic PD-L1 staining. CD8+ PD-1high was defined by the cohort median PD-1+ fraction (35.6%). Patients were stratified by CTC PD-L1 status and CD8+ PD-1 (high/low). The primary endpoint was progression-free survival (PFS); overall survival (OS) and objective response rate (ORR) were secondary endpoints.ResultsFifty-seven patients (45.2%) were CTC PD-L1–positive. Median PFS was longest in the PD-L1+/PD-1high group (14.2 months) versus the other three groups (8.5, 6.3, and 4.8 months; p<0.001). ORR followed a similar gradient (41.9%, 30.8%, 22.9%, and 14.7%; p=0.021). After adjustment for baseline covariates, dual-biomarker status remained independently associated with PFS (HR=0.48, 95% CI 0.32–0.72; p<0.001) and OS (HR=0.53, 95% CI 0.35–0.80; p=0.002).ConclusionThis dual liquid-biopsy approach was associated with response and survival in this retrospective advanced NSCLC cohort receiving ICIs, supporting its potential for prognostic stratification; prospective validation is needed.

BackgroundLow-Dose Computed Tomography (LDCT) is commonly used to detect pulmonary nodules; however, it may also contribute to overdiagnosis. DNA methylation shows promise as an approach to discriminate early-stage lung cancer (LC) patients from individuals with benign nodules (hereafter referred to as benign pulmonary nodule group) and healthy individuals.MethodsThis study investigated the performance of DNA methylation in three genes (TAC1, SOX17, and RASSF1A) in plasma-derived cell-free DNA (cfDNA) for discriminating LC patients from benign and healthy individuals (collectively referred to as benign/healthy individuals). We enrolled 149 LC patients (96 with early-stage [stage IA] and 53 with advanced-stage [non-IA]), 54 benign pulmonary nodule group, and 75 healthy individuals.ResultsMethylation-positive rates for all three genes were significantly higher in LC patients compared to benign/healthy individuals. A combined three-gene model based on the ΔCt values of the three genes demonstrated robust diagnostic performance, achieving a sensitivity of 97.7%, specificity of 96.6%, and an area under the curve (AUC) of 0.99 for discriminating LC patients from benign/healthy individuals. Furthermore, another combined three-gene model based on the ΔCt values of the same genes showed high diagnostic performance for discriminating IA-stage LC patients from benign/healthy individuals, with a sensitivity of 96.9%, specificity of 88.54%, and AUC of 0.95.ConclusionThis study highlights the robust diagnostic value of a combined three-gene (TAC1, SOX17, and RASSF1A) methylation model for detecting LC, including early-stage disease, offering high sensitivity and specificity.

BackgroundThe Prognostic Nutritional Index (PNI) is a numerical score used to assess the nutritional and immunological status, derived from serum albumin concentration and lymphocyte count. While malnutrition and systemic inflammation are known to influence surgical outcomes and cancer prognosis, the predictive value of PNI in colorectal cancer (CRC) is underexplored. This study aimed to evaluate whether preoperative PNI predicts postoperative complications and long-term survival in patients with CRC undergoing curative-intent surgery.MethodsThe records of 2,026 patients who underwent curative-intent surgery for CRC between 2011 and 2023 at a tertiary center in Taiwan were retrospectively reviewed. Propensity score matching (PSM) was used and patients were stratified into high and low PNI groups based on the median value. Outcomes included in-hospital complications, 5-year overall survival (OS), and disease-free survival (DFS) in the subgroup of patients with stage I–III disease. Multivariable logistic regression and Cox proportional hazards models were used as well as restricted cubic spline (RCS) analysis.ResultsHigh PNI was independently associated with lower rates of overall complications (adjusted odds ratio [aOR] = 0.22, 95% confidence interval [CI]: 0.17–0.28), ileus (aOR = 0.23), anastomotic leakage (aOR = 0.16), and lung-related complications (aOR = 0.38). High PNI was also significantly associated with improved 5-year OS (aHR = 0.45, 95% CI: 0.38–0.55), but not DFS. In additional competing-risk and comorbidity-stratified analyses, high PNI remained protective for both cancer-related (p = 0.0005) and non–cancer-related mortality (p < 0.0001), with consistent effects across CCI strata and attenuation for cancer-related death in CCI ≥ 3 (p = 0.1024). Additionally, PNI demonstrated superior predictive performance over the neutrophil-to-lymphocyte ratio (NLR) for all complication types based on receiver operating characteristic (ROC) analysis.ConclusionPreoperative PNI was independently associated with postoperative complications and OS in patients with CRC undergoing curative surgery. Routine assessment of PNI may help refine risk stratification and guide perioperative management to improve surgical outcomes.

ObjectiveThis study aimed to integrate bioinformatics, network pharmacology, and single-cell sequencing to explore the potential neuro-immune mechanisms by which the traditional Chinese medicine formula Xiao-Yao-San (XYS) ameliorates chronic stress-induced colorectal cancer (CRC) progression.MethodsTranscriptomic and survival data of CRC patients were obtained from public databases (TCGA, GEO). Combined with literature review, 130 neurotransmitter-related receptor genes (NRGs) were screened, and their expression and prognostic value in CRC were analyzed. Based on 51 XYS components previously identified by UHPLC/Q-TOF-MS, network pharmacology was employed to predict their potential targets (1,228 in total). These targets were intersected with differentially expressed NRGs. Molecular docking was further performed to evaluate the binding affinity between XYS components and receptors. A mouse model of chronic unpredictable mild stress (CUMS) combined with orthotopic CRC transplantation was established. Neurotransmitter levels were measured by mass spectrometry, and 10x Genomics single-cell transcriptomic sequencing was applied to analyze changes in the tumor immune microenvironment.ResultsBioinformatics analysis revealed that 100 NRGs were significantly dysregulated in CRC tissues. After intersecting with XYS targets, 14 potential NRGs were identified, among which seven (ADRA2C, DRD1, GABRA2, HTR1B, HTR1D, HTR2A, HTR2B) showed significant correlation with patient prognosis. Molecular docking demonstrated favorable binding activity between XYS components (such as 8-Debenzoylpaeoniflorin and Sucrose) and the hub NRGs. In vivo experiments confirmed that XYS reversed CUMS-induced abnormalities in tumor and plasma levels of norepinephrine, dopamine, and serotonin. Single-cell sequencing further indicated that XYS reduced the CUMS-induced increase in myeloid-derived suppressor cell (MDSC) proportion and modulated the expression of key NRGs, including HTR2A in macrophages and HTR1B in T cells. KEGG enrichment analysis suggested that neuroactive ligand-receptor interaction and immune-related pathways were significantly regulated upon XYS intervention.ConclusionXYS modulates neurotransmitter homeostasis and the tumor immune microenvironment in CRC under chronic stress through a multi-component and multi-target manner, which is closely associated with the regulation of key NRGs such as HTR1B and DRD1. This study provides neuro-immunological evidence for the clinical application of XYS in CRC patients with emotional disorders.

PurposeTo investigate independent risk factors and construct an internally validated risk prediction model for invasive pulmonary fungal infection (IPFI) in patients with lung cancer.Patients and MethodsClinical data from 250 consecutive lung cancer inpatients admitted to Nanchong Central Hospital between February 2022 and March 2025 were retrospectively analyzed; 41 patients developed IPFI and 209 did not. Patients were randomly assigned to a training set (n=175) and a validation set (n=75) at a 7:3 ratio. Candidate predictors were screened by univariate logistic regression, reduced using least absolute shrinkage and selection operator (LASSO) regression with 10-fold cross-validation, and entered into multivariable logistic regression to construct a nomogram. Model performance was evaluated using bootstrap internal validation (1000 resamples), calibration curves and goodness-of-fit testing, receiver operating characteristic analysis, and decision curve analysis.ResultsDiabetes mellitus, invasive procedures, systemic glucocorticoid use, lower CD4+ T-cell count, and length of hospital stay >14 days were associated with IPFI and were retained as independent predictors in the final model. The model showed good discrimination, with an area under the curve of 0.876 (95% CI: 0.809–0.944) in the training set and 0.861 (95% CI: 0.750–0.973) in the validation set, and demonstrated clinical net benefit across threshold probability ranges of 0.03–0.90 (training) and 0.04–0.78 (validation).ConclusionThis nomogram may support early risk stratification for IPFI among lung cancer inpatients, while confirmation in external, multi-center cohorts is needed before broader clinical application.