Preoperative diagnosis of ductal carcinoma in situ (DCIS) may be followed by pathological upstaging to invasive ductal carcinoma (IDC) upon surgical excision, a discrepancy that significantly impacts surgical planning and decisions regarding sentinel lymph node biopsy (SLNB). This retrospective study aimed to evaluate clinical indicators associated with such upstaging and develop a nomogram-based clinical estimation model for risk stratification. We reviewed medical records of all consecutively diagnosed patients (n = 445) initially diagnosed with DCIS via core needle biopsy (CNB) or vacuum-assisted biopsy (VAB) between 2013 and 2022 at a single institution. Demographic, imaging, clinicopathological, immunohistochemical, and blood-based biomarkers were categorized and analyzed. Logistic regression analysis was employed to identify independent predictors, from which a visual risk estimation tool was constructed. Among the 445 patients, 137 (30.8%) were upstaged to IDC. In the multivariable analysis, clinical tumor size > 1.5 cm, biopsy modality, and high histologic grade at biopsy emerged as independent predictors of pathological upstaging. Notably, VAB was associated with a lower rate of underestimation than CNB. Subgroup analyses revealed that age > 50 years, larger lesion size, and high grade were associated with upstaging in the CNB group, whereas histologic grade was the primary predictor in the VAB group. The nomogram demonstrated modest discriminative performance (AUC = 0.690) for individualized preoperative assessment. In conclusion, clinical tumor size, biopsy method, and histologic grade provide valuable information for estimating the likelihood of occult invasive disease in patients with preoperative DCIS.
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation and progressive joint damage. Although ferroptosis has been implicated in RA progression, the role of disulfidptosis and its interaction with ferroptosis remains unclear. This study aimed to identify Disulfidptosis- and Ferroptosis-Related Genes (DFRGs) associated with RA and construct a candidate diagnostic model. Blood transcriptomic data from 154 RA patients and 43 healthy controls were analyzed. Differentially expressed DFRGs were identified, and immune infiltration was assessed using single-sample Gene Set Enrichment Analysis (ssGSEA). Feature genes were selected through correlation analysis and logistic regression, followed by construction of a diagnostic nomogram. External validation was performed using independent datasets. Potential regulatory miRNAs and therapeutic agents were predicted, and single-cell eQTL-based Mendelian randomization (MR) was used to evaluate genetic associations between core gene expression and RA risk. Eleven DFRGs were identified and were enriched in p53, mTOR, and immune-related pathways. Five feature genes, DUOX1, DRD4, ATP6V1G2, ASNS, and CDKN1A, were used to establish a diagnostic model with favorable performance in the training cohort and external validation datasets. Five key miRNAs and 61 potential therapeutic agents were predicted. MR suggested that ASNS expression may be protective, whereas ATP6V1G2 expression may increase RA risk. These findings suggest that DFRGs-related signatures may be involved in RA pathogenesis and immune dysregulation, although further in vitro and in vivo validation is required.
This study aimed to elucidate the role of the RNA-binding protein embryonic lethality abnormal vision-like protein 1 (ELAVL1) in the pathogenesis of allergic rhinitis (AR), specifically by investigating its potential to promote T helper 2 (Th2) cell differentiation by regulating the stability of carboxypeptidase A3 (CPA3) mRNA. Differentially expressed genes associated with AR were screened via bioinformatic analysis. Nasal mucosal tissues were collected from 42 children with AR and 42 healthy controls. CPA3 was significantly upregulated in the nasal mucosal tissues of AR patients. CD4+ T cells were isolated from the peripheral blood of healthy volunteers, polarized toward Th2 differentiation, and subjected to cell transfection experiments to examine the effect of CPA3 on Th2 differentiation. An ovalbumin (OVA)-induced AR mouse model was established. Knockdown of CPA3 alleviated nasal symptoms (e.g., scratching and sneezing), attenuated pathological damage in the nasal mucosa (characterized by reduced edema and inflammatory cell infiltration), and suppressed Th2 immune responses (decreased interleukin-4 and immunoglobulin E levels, reduced Th2 cell proportion, and downregulated GATA binding protein 3 expression) in AR mice. ELAVL1 bound to CPA3 mRNA and enhanced its stability, thereby upregulating CPA3 expression; a positive correlation was observed between their expression levels in AR. Overexpression of CPA3 reversed the alleviating effects of ELAVL1 knockdown on nasal symptoms and Th2 immune responses in AR mice. Taken together, these results demonstrate that targeting the ELAVL1/CPA3 axis may provide a novel therapeutic strategy for AR.
Minimal hepatic encephalopathy (MHE) involves subtle cognitive dysfunction and systemic inflammation and is associated with an increased risk of overt hepatic encephalopathy. The Animal Naming Test (ANT1) is a rapid semantic fluency tool for MHE assessment, but its performance across different primary spoken languages remains unclear. We conducted a prospective proof-of-concept study to evaluate the diagnostic performance of ANT1 and serum interleukin-6 (IL-6) in Mandarin- and Taiwanese Hokkien-speaking cirrhotic patients. A total of 65 cirrhotic patients and 34 healthy controls were enrolled. Patients completed ANT1, simplified ANT1 (S-ANT1), and standard psychometric assessments. MHE was defined by abnormal PHES and/or visually assessed EEG slowing. Diagnostic discrimination was evaluated using AUROC analyses stratified by primary spoken language. A post hoc exploratory Taiwanese-calibrated S-ANT1 was also assessed in Taiwanese Hokkien-speaking patients. Sixteen cirrhotic patients (24.6%) were diagnosed with MHE. Patients with MHE had lower ANT1 scores and higher serum IL-6 levels than those without MHE. In Mandarin-speaking patients (n = 44), ANT1 demonstrated an AUROC of 0.760, while serum IL-6 showed an AUROC of 0.841. The composite model combining ANT1 and serum IL-6 showed a numerically higher AUROC of 0.895, but this improvement was not statistically significant in pairwise DeLong comparisons. In Taiwanese Hokkien-speaking patients (n = 21), standard ANT1 showed a lower AUROC of 0.679. The exploratory Taiwanese-calibrated S-ANT1 showed a numerically higher AUROC of 0.776; however, this post hoc finding was based on a small subgroup with 7 MHE events and requires external validation. This study suggests that primary spoken language may be associated with ANT1 performance in MHE assessments. Integrating ANT1 with serum IL-6 showed numerically improved discrimination in Mandarin speakers, whereas exploratory demographic calibration of S-ANT1 showed a numerically higher AUROC in Taiwanese Hokkien speakers. These findings are exploratory and hypothesis-generating, necessitating validation in larger independent cohorts before clinical implementation.
Sepsis-induced organ failure involves dysregulated neutrophil responses, including neutrophil extracellular trap (NET) formation, via NETosis. Exosomes generated from adipose-derived stem cells (ADSCs) have shown potential in sepsis treatment. This study characterized organ-specific NETosis in the kidney, liver, and lungs using a murine cecal ligation and puncture (CLP) model and assessed the modulatory effects of ADSC exosomes. Male C57BL/6 mice were grouped as follows: control, CLP, and CLP with ADSC exosome therapy (n = 6 per group). Plasma cell-free DNA (cfDNA) and tissue citrullinated histone H3 (CitH3) levels were measured at 16 h postoperatively. Confocal immunofluorescence was performed by co-staining for CitH3 and Ly6G. Organ-derived Ly6G-enriched neutrophils were subjected to quantitative reverse transcription polymerase chain reaction for seven NETosis-related genes: CYBB, Padi4, H2ac20, H2bc21, Nlrc4, Nlrp3, and Ripk3. CLP significantly elevated plasma cfDNA and lung CitH3 levels, whereas ADSC exosome treatment reduced both. Kidney and liver CitH3 levels remained unchanged across the groups. Confocal imaging confirmed active NETosis predominantly in the lung, with minimal signals in the kidneys and liver. In kidney and liver neutrophils, only Nlrp3 and Ripk3 were significantly upregulated by CLP. In the lungs, all seven genes were significantly elevated; ADSC exosomes significantly reduced Padi4, H2ac20, Nlrp3, and Ripk3. CLP-induced NETosis was more pronounced in the lungs at the protein and transcriptional levels, where ADSC exosomes broadly suppressed NETotic pathways. NETosis reduction by ADSC exosomes was not observed in renal and hepatic neutrophils, indicating their possible protective role in sepsis within the pulmonary system.
WT1-associated protein (WTAP), a core component of the methyltransferase complex, is involved in various tumor pathological processes, but its specific mechanism in cervical cancer (CC) remains unclear. This study, based on single-cell transcriptomic data (including 3 CC and 2 normal tissues), constructed a CC microenvironment cell atlas through unsupervised clustering and identified a novel malignant subpopulation, TXNDC5+ epithelial cells (TXNDC5+EPCs). This epithelial subpopulation was specifically enriched in cancerous tissues compared to normal tissues. Furthermore, within the TXNDC5+EPC subpopulation, WTAP and TXNDC5 were co-expressed. In vitro experiments demonstrated that knocking down WTAP reduced the m6A modification level, mRNA stability, and expression of TXNDC5. RIP experiments confirmed their direct binding. In CCK-8, colony formation, Transwell assays, flow cytometry, and Western Blot analysis, WTAP knockdown inhibited cell proliferation/migration and accelerated apoptosis, while TXNDC5 overexpression reversed these effects. This study is the first to elucidate that the TXNDC5+EPC subpopulation is a dominant malignant driver in CC, regulated by WTAP-mediated m6A post-transcriptional modification. Targeting the WTAP-TXNDC5 axis holds promise as a novel therapeutic strategy for CC, directing a new pathway for clinical intervention.
Aspartyl-tRNA synthetase 2 (DARS2), the mitochondrial enzyme responsible for aminoacylation of aspartyl-tRNA, is traditionally known for its effect on protein synthesis. Recently, DARS2 is reported to be implicated in tumorigenesis. However, its specific effect on breast cancer (BC) is poorly understood. The present work employed bioinformatics tools for analyzing DARS2 expression among BC patients and its association with clinicopathological characteristics and patient prognosis. We evaluated DARS2 expression within BC cells and tissues and assessed how DARS2 knockdown or PI3K pathway activation affected cell growth, migration, invasion, apoptosis, as well as cell cycle progression. Mechanistically, we analyzed how DARS2 regulated the PI3K/Akt/GSK-3β/β-catenin pathway. Additionally, a xenograft tumor model was constructed to validate our in vitro findings. According to our observations, DARS2 expression significantly increased in BC cells and tissues. Knockdown of DARS2 markedly suppressed cell growth, invasion, migration, and epithelial-mesenchymal transition (EMT), but enhanced their apoptosis. Mechanistic studies revealed that DARS2 knockdown suppressed the PI3K/Akt/GSK-3β/β-catenin pathway, whereas PI3K pathway activation with 740Y-P reversed the impacts of DARS2 knockdown. In vivo experimental results further verified that DARS2 suppression significantly suppressed tumor growth and metastasis through downregulating the PI3K/Akt/GSK-3β/β-catenin pathway. Collectively, these results indicate that DARS2 promotes the growth, migration, invasion, and EMT of BC cells by regulating the PI3K/Akt/GSK-3β/β-catenin signaling pathway.
The instability of atherosclerotic plaques, particularly intraplaque hemorrhage (IPH), drives life-threatening cardiovascular events, a process in which vascular smooth muscle cell (VSMC)-derived foam cells play a significant role. We aim to identify key biomarkers associated with VSMC-derived foam cells and IPH by analyzing data from human IPH datasets and VSMC-derived foam cell datasets (GSE163154, GSE68021, GSE28829, and GSE43292). Weighted gene co-expression network analysis (WGCNA), differential expression analysis, and machine learning algorithms (LASSO and SVM-RFE) were employed to identify hub genes. The identified genes were validated in independent datasets and in experimental models, including oxidized low-density lipoprotein-stimulated VSMCs and atherosclerotic aortic tissues of high-fat diet-fed ApoE-/- mice. Transcription factor (TF) prediction and dual-luciferase reporter assays were performed to explore upstream regulatory mechanisms. We identified CD68 and CYBA as key hub genes significantly upregulated in both VSMC-derived foam cells and unstable atherosclerotic plaques, with high diagnostic accuracy (AUC > 0.9) by ROC analysis. Experimental validation confirmed their upregulated expression. FOXC1 was identified as a common upstream transcription factor regulating both CD68 and CYBA. FOXC1 protein levels were elevated in VSMC-derived foam cells, and dual-luciferase assays confirmed its direct activation of CD68 and CYBA promoters. FOXC1 overexpression promoted CD68 and CYBA expression and enhanced lipid accumulation in VSMCs, while FOXC1 knockdown exerted opposite effects. Immune infiltration analysis revealed significant correlations between these hub genes and immune cell populations in unstable plaques. This study identifies FOXC1 as a key TF regulating CD68 and CYBA expression, thereby promoting VSMC-derived foam cell formation and plaque instability.
This study aimed to investigate associations of plasma and synovial fluid vascular endothelial growth factor A (VEGF-A) and neuropilin-1 (NRP1) levels with radiographic severity, pain sensitization-related features, and disease burden in knee osteoarthritis (KOA). Plasma VEGF-A and NRP1 were measured by sandwich ELISA in 120 patients with KOA (Kellgren-Lawrence [KL] grade 2, n = 40; grade 3, n = 52; grade 4, n = 28) and 53 healthy controls, while synovial fluid VEGF-A and NRP1 were assessed in the KOA group. Pain sensitization-related features and disease burden were evaluated using the Central Sensitization Inventory (CSI), pressure pain threshold (PPT), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and visual analog scale (VAS). Plasma VEGF-A and NRP1 levels were elevated in KOA patients versus healthy controls and increased with KL grade, while synovial fluid VEGF-A and NRP1 rose with radiographic severity. Synovial fluid VEGF-A showed stronger discriminatory performance for radiographic severity than synovial fluid NRP1. After the Benjamini-Hochberg FDR correction, plasma and synovial fluid VEGF-A/NRP1 remained associated with VAS, WOMAC, CSI-defined symptom burden, and local PPT in the overall KOA cohort. Multivariable regression adjusted for KL grade, age, sex, BMI, and symptom duration showed that synovial fluid VEGF-A had the strongest independent associations with clinical outcomes. Bootstrap-validated combined ROC models, particularly those incorporating VEGF-A, showed good discriminatory performance for KOA status and severity stratification. These findings suggest that the VEGF-A-NRP1 axis, particularly synovial fluid VEGF-A, may serve as a biomarker framework for KOA severity assessment and symptom-related phenotyping.
Extracorporeal shock wave therapy (ESWT) improves tendon-bone healing after rotator cuff injury (RCI), but its underlying cellular mechanisms remain unknown. This study aimed to explore the therapeutic effects of ESWT on RCI, with a particular focus on endothelial cells and tenocytes. The RCI model was established in rabbits by rotator cuff tear surgery, followed by ESWT intervention. Histological evaluation, blood perfusion analysis, biomechanical testing, and assessment of inflammation and extracellular matrix (ECM) degradation were performed in RCI-treated rabbits at week (W) 2, W4, and W8. For the in vitro experiments, human umbilical vein endothelial cells (HUVECs) and human tenocytes were treated with ESWT. ESWT reduced Bonar scores, increased the fibrocartilage area and collagen-positive area, and enhanced blood perfusion and biomechanical strength at most time points in RCI rabbits (all p < 0.05). Moreover, ESWT reduced inflammation and ECM degradation, as reflected by reduced tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 and decreased matrix metalloproteinase (MMP)-1 and MMP-9 at most time points in RCI rabbits (all p < 0.05). In HUVECs, ESWT increased proliferation, invasion, branch points, MMP-2, MMP-9, vascular endothelial growth factor A (VEGFA), and fibroblast growth factor 2 (FGF2) (all p < 0.05). In tenocytes, ESWT increased proliferation, collagen I, thrombospondin-4 (TSP4), VEGFA, FGF2, tenomodulin (TNMD), and scleraxis (SCX) (all p < 0.05). ESWT improves tendon integrity, blood perfusion, and biomechanical strength while reducing inflammation and ECM degradation after RCI, possibly via enhanced angiogenic activity in endothelial cells and maintenance of the tenogenic phenotype in tenocytes.
The impacts of cardiometabolic risk factors (CMRFs) and the biomarkers on disease severity in metabolic dysfunction-associated steatotic liver disease (MASLD) remain elusive. Accordingly, a multicenter study by recruiting MASLD patients from a nationwide registry database was conducted with a total of 2882 MASLD patients (54.1% males, mean age = 55.6 ± 13.9 years, mean body mass index [BMI] = 28.1 ± 4.9 kg/m2) being recruited. The proportions of patients carrying CMRFs of overweight/obesity, hypertension, hypertriglyceridemia, low high-density lipoprotein cholesterol level, and diabetes/prediabetes were 91.2%, 74.5%, 54.8%, 59.6%, and 74.5%, respectively. There was a significant linear trend between significant fibrosis and CMRFs (5.1%, 27%, and 54.6% in patients with one CMRF, 3 CMRFs, and ≥ 4 CMRFs, respectively, p = 0.009). The adjusted odds ratios (aOR) with 95% confidence intervals (CIs) for advanced fibrosis in patients of hemoglobin A1c (HbA1c) 5.7%-6.5%, 6.5%-8.0%, and > 8.0% were 1.02 (95% CI = 0.68-1.53, p = 0.93), 1.83 (95% CI = 1.16-2.88, p = 0.01), and 2.78 (95% CI = 1.45-5.34, p = 0.002), respectively. The significant risk factors for advanced fibrosis in MASLD were age > 60 years (aOR = 12.08, 95% CI = 6.23-23.46, p < 0.001), elevated transaminase level (aOR = 1.06, 95% CI = 1.05-1.09, p < 0.001), and diabetes (aOR = 1.51, 95% CI = 1.02-2.26, p = 0.04). In conclusion, there was a significant linear association between advanced fibrosis and the items of CMRFs. The HbA1c level could serve as a predictive biomarker for advanced fibrosis in MASLD with the implication that diabetes control is mandatory for patients with MASLD.
The prognostic effect of concurrent metabolic dysfunction-associated steatotic liver disease (MASLD) on outcomes for hepatocellular carcinoma (HCC) patients remains unclear. The Prognostic Nutritional Index (PNI) reflects nutritional and inflammatory status and is a well-known prognostic factor. We therefore aimed to evaluate and compare the prognostic role of PNI in patients with HCC with and without concurrent MASLD undergoing curative surgical resection. In our retrospective study, 991 patients undergoing curative HCC resection were stratified according to MASLD status and pre-operative PNI (cut-off: 45). Overall survival (OS) and recurrence-free survival (RFS) were analyzed using Kaplan-Meier methods and Cox proportional hazards models. Further subgroup analysis was performed according to their concurrent viral hepatitis status. High PNI was identified as an independent protective factor against poor OS for the entire cohort (hazard ratio [HR]: 0.65; 95% confidence interval [CI]: 0.49-0.87, p = 0.004). The Kaplan-Meier analysis showed that the high-PNI/MASLD group had the best OS, while the low-PNI/no-MASLD group had the worst. Subgroup analysis indicated that high PNI was an independent protective factor for OS only in the no-MASLD group (HR: 0.59, p = 0.003) but not the MASLD group (HR: 0.94, p = 0.793). Its prognostic effect was more significant in HCC patients without concurrent MASLD or with chronic hepatitis B. To conclude, a better nutritional status, assessed by PNI, is a valuable prognostic marker for patients with HCC. Its protective effect on OS is significantly pronounced in patients without concurrent MASLD, indicating that MASLD status modifies the prognostic utility of PNI.
Tumors are highly heterogeneous, and whole-lesion radiomics analysis is a popular method for extracting texture features that reflect this heterogeneity, which can be used to build models for cancer diagnosis, staging, therapy response evaluation, and prognosis prediction. However, there is no spatial information for understanding which components provide the most critical information. Recently, habitat analysis has gained widespread attention, and it is used to divide a tumor into distinct sub-regions, called habitats, that share common characteristics. CT reveals heterogeneity in attenuation, texture, entropy, and enhancement patterns, which can be used to generate habitats. In the past 2 years, many studies exploring the role of CT habitats have been reported. The divided habitats can be used to build models for the classification of histological or molecular subtypes, the evaluation and prediction of treatment response, and prognostication of progression-free survival or overall survival. This review aims to summarize studies on the application of CT-habitat analysis for cancer management. In addition to clinical applications, various methods for habitat segmentation will be reviewed. Lastly, how spatial information revealed by the habitat can guide tissue biopsy for tissue-level confirmation studies will be described, which is critical for understanding the underlying biology and paving the way for future clinical implementation.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with diverse manifestations, including rash, arthritis, and nephritis. Although autoantibodies are a key feature of SLE, their levels often poorly reflect disease severity, suggesting the involvement of additional contributing factors. The tripartite motif-containing protein (TRIM) family, which regulates immunity, may play a role in SLE. Although TRIM21 is a known autoantigen, the roles of other TRIM family members remain unclear. The present study examined TRIM expression in SLE and evaluated the potential of TRIM proteins as biomarkers. TRIM expression in peripheral blood mononuclear cells was measured using reverse transcription quantitative polymerase chain reaction (PCR) and compared between patients with SLE (n = 33) and healthy controls (n = 20). Associations of TRIM expression with disease activity (active/inactive), renal involvement (nephritis/nonnephritis), clinical manifestations, and laboratory parameters were analyzed. The expression levels of several TRIM genes, specifically TRIM5, TRIM11, TRIM21, and TRIM72, were higher in patients with inactive SLE, nonnephritic disease, or low disease activity than in patients with active disease, nephritic disease, or relapsed SLE and healthy controls. The expression levels of these genes were considerably and negatively associated with clinical symptoms but not laboratory parameters. Hydroxychloroquine users exhibited higher levels of TRIM21 expression than did nonusers. Overall, specific TRIM proteins are inversely correlated with SLE disease activity and clinical phenotypes, which indicates their potential as biomarkers. Hydroxychloroquine may regulate TRIM21 expression. Further investigation into underlying mechanisms and continued TRIM monitoring are necessary to develop new SLE treatments and better assess disease progression.
This retrospective study aimed to explore the value of DAT-FAT serological profiles confirmed by AET in classifying neonatal jaundice, evaluating its severity, and guiding clinical management. A total of 915 jaundiced newborns (584 pathological, 331 physiological) admitted from July 2018 to August 2021 were included. Univariate and multivariate logistic regression analyses were conducted to identify risk factors. To assess predictive ability for jaundice type and early risk stratification of jaundice severity, the 426 patients with ABO incompatibility were stratified into subgroups based on the results of the DAT-FAT-AET serological panel. Maternal pregnancy count, gestational weeks, direct bilirubin at admission, and ABO incompatibility were identified as independent predictors of jaundice type (p < 0.05). Those who tested triple-positive in the DAT-FAT-AET serological panel (Group 2) had the highest predictive value for pathological jaundice (area under the curve, 0.920 [0.788-0.994]), indicating the maximum severity of pathological jaundice (p < 0.01). AET serves as the definitive criterion for confirming ABO-incompatible jaundice, while DAT-FAT profiles enable early risk stratification of severity. Subgrouping by AET-confirmed DAT-FAT serology helps assess etiology and severity in ABO-incompatible neonatal jaundice, supporting clinical early risk stratification.
This retrospective cohort study utilized the Medical Information Mart for Intensive Care database to investigate the association between the triglyceride-glucose (TyG) index and in-hospital intensive care unit (ICU) readmission in patients with ischemic stroke (IS). Among 2929 patients, 24.0% experienced ICU readmission. Logistic regression analysis demonstrated that the continuous TyG index was associated with a 17% higher risk of ICU readmission (odds ratio [OR], 1.17; 95% confidence interval [CI], 1.01-1.36; p = 0.04). Compared with the lowest quartile (Q1), the higher TyG index quartiles showed a progressively increased risk of ICU readmission (Q2: OR, 1.49; 95% CI, 1.13-1.96; Q3: OR, 1.46; 95% CI, 1.10-1.95; Q4: OR, 1.53; 95% CI, 1.14-2.05; P for trend = 0.02). Restricted cubic spline analysis revealed a significant nonlinear relationship (P for nonlinearity = 0.027), with an inflection point at a TyG index value of 9.82 (P for log-likelihood ratio = 0.007). Incorporating the TyG index into conventional models significantly improved the predictive performance for ICU readmission, as evidenced by increases in the area under the curve, net reclassification improvement and integrated discrimination improvement. In conclusion, an elevated TyG index was associated with an increased risk of in-hospital ICU readmission in patients with IS and exhibited a nonlinear dose-response relationship. The TyG index enhanced the predictive accuracy of existing scoring tools, suggesting its potential clinical value for risk stratification and early intervention.
This study aimed to evaluate the predictive value of the estimated dose of radiation to immune cells (EDRIC) in patients with esophageal cancer receiving radical radiotherapy. We retrospectively reviewed the data of patients with esophageal cancer who underwent definitive radiotherapy at our institution. The Kaplan-Meier method and log-rank test were used to assess the survival curves. Univariate and multivariate Cox regression analyses were performed to identify the prognostic factors associated with overall survival (OS) and progression-free survival (PFS). Additionally, binary logistic regression analyses were used to identify factors associated with severe lymphopenia. A total of 166 patients, with a median follow-up duration of 59 months, were evaluated. The median EDRIC was 7.23 Gy. The 1-, 3-, and 5-year OS rates were 81.9%, 49.4%, and 33.7% in the EDRIC < 7.23 Gy group, compared with 62.7%, 21.7%, and 19.3% in the EDRIC ≥ 7.23 Gy group (p < 0.001). Prognostic analysis identified Eastern Cooperative Oncology Group performance status, TNM stage, treatment, EDRIC, and lymphopenia as significant independent prognostic factors of OS (p < 0.05). Higher EDRIC, N stage, and lymphopenia were identified as independent risk factors for PFS. Logistic regression analysis indicated that treatment and EDRIC were significantly associated with severe lymphopenia (p < 0.05). EDRIC serves not only as a prognostic marker for radical radiotherapy in esophageal cancer, but also as a potential biomarker for radiation-induced lymphopenia.
