Risk Factors of Distant Metastatic Parathyroid Carcinoma and Insights into Therapeutic Perspectives.

BACKGROUND: Distant metastatic parathyroid carcinoma (DM-PC) is a rare but often lethal entity with limited data about prognostic indicators. We sought to investigate the risk factors, patterns, and outcomes of DM-PC. METHODS: In this observational cohort study, 126 patients who underwent surgery for PC at a tertiary referral center from 2010 to 2023 were enrolled, among whom 38 had DMs. Univariate and multivariate Cox regression analyses were used to assess the effects of prognostic factors on DM. RESULTS: The cumulative incidence of DM was 14.1%, 33.8%, and 66.9% at 5, 10, and 20 years in the duration of disease course, respectively. DM-PC patients suffered a worse 5-year overall survival of 37.1% compared with 89.8% in the non-DM patients (p < 0.001). DM-PC patients also suffered more previous operations (p < 0.001), higher preoperative serum calcium (p<0.001) and parathyroid hormone (PTH) levels (p < 0.001), lower frequencies of R0 resection (p < 0.001), higher rates of pathological vascular invasion (p = 0.020), thyroid infiltration (p = 0.027), extraglandular extension (p = 0.001), upper aerodigestive tract (UAT) invasion (p < 0.001), and lymph node metastasis (p < 0.001). Multivariate Cox regression revealed that non-R0 resection (HR 6.144, 95% CI 2.881-13.106, p < 0.001), UAT invasion (HR 3.718, 95% CI 1.782-7.756, p < 0.001), and higher preoperative PTH levels (HR 1.001, 95% CI 1.000-1.001, p = 0.012) were independent risk factors of DM. CONCLUSIONS: Upper aerodigestive tract invasion and higher preoperative PTH levels might be risk factors for possible metastatic involvement of PC. R0 resection and closer surveillance should be considered in such cases to minimize the risk of DM and to optimize patient care.

Deciphering three predominant biopsy-proven phenotypes of IgG4-associated kidney disease: a retrospective study.

Background: IgG4-associated kidney disease (IgG4-RKD) encompasses a spectrum of disorders, predominantly featuring tubulointerstitial nephritis (TIN) and membranous glomerulonephropathy (MGN). The limited understanding of the co-occurrence of IgG4-RD-TIN with anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) poses a diagnostic and therapeutic challenge. Methods: We examined 49 cases, comprising 21 cases of IgG4-RD-TIN (group A), 10 cases of IgG4-RD-TIN accompanied with MGN (group B), and 18 cases of IgG4-RD-TIN concurrent with AAV (group C), at the First Affiliated Hospital of Zhejiang University, China, from June 2015 to December 2022. Results: The mean age and gender of the three IgG4-RKD subtypes were not statistically significant. IgG4-RD-TIN exhibited higher serum creatinine and a higher incidence of hypocomplementemia (group A 47.6%, group B 30%, group C 16.7%). IgG4-RD-TIN-MGN was characterized by proteinuria (group A 0.3 g/d, group B 4.0 g/d, group C 0.8 g/d, P < 0.001) and hypoalbuminemia. IgG4-RD-TIN-AAV exhibited hypohemoglobinemia (group A 103.45 g/l, group B 119.60 g/l, group C 87.94 g/l, P < 0.001) and a high level of urine erythrocytes. The primary treatment for IgG4-RD-TIN was steroids alone, whereas IgG4-RD-TIN-MGN and IgG4-RD-TIN-AAV necessitated combination therapy. Group A experienced two relapses, whereas groups B and C had no relapses. There was no significant difference in patient survival among the three groups, and only two cases in group C suffered sudden death. Conclusions: This study provides valuable insights into clinical manifestations, auxiliary examination features, pathological characteristics, and prognosis of IgG4-RD-TIN, IgG4-RD-TIN-MGN, and IgG4-RD-TIN concurrent AAV. Large-scale studies are required to validate these findings.

Detection and identification of circulating tumor cells in parathyroid tumors and correlation analysis with clinicopathological features.

INTRODUCTION: The differential diagnosis of parathyroid carcinoma (PC)/parathyroid adenoma (PA) in parathyroid tumors is critical for their management and prognosis. Circulating tumor cells (CTCs) identification in the peripheral blood of parathyroid tumors remains unknown. In this study, we proposed to investigate the differences of CTCs in PC/PA and the relationship with clinicopathologic features to assess its relevance to PC and value in identifying PC/PA. METHODS AND MATERIALS: Peripheral blood was collected from 27 patients with PC and 37 patients with PA treated in our hospital, and the number of chromosome 8 aberrant CTCs was detected by negative magnetic bead sorting fluorescence in situ hybridization (NE-FISH). The differences of CTCs in PC/PA peripheral blood were compared and their diagnostic efficacy was evaluated, and the correlation between CTCs and clinicopathological features of PC was further explored. RESULTS: CTCs differed significantly in PC/PA (p = 0.0008) and were up-regulated in PC, with good diagnostic efficacy. CTCs combined with alkaline phosphatase (ALP) assay improved the diagnostic efficacy in identifying PC/PA (AUC = 0.7838, p = 0.0001). The number of CTCs was correlated with tumor dimensions, but not significantly correlated with clinical markers such as calcium and PTH and pathological features such as vascular invasion, lymph node metastasis and distant metastasis. CONCLUSION: As a non-invasive liquid biopsy method, CTCs test combined with ALP test can be used as an important reference basis for timely and accurate identification and treatment of PC. It is of great significance to improve the current situation of PC diagnosis, treatment and prognosis.

Highly efficient catalytic Fenton-Like reactions of bimetallic Fe/Cu chelated on radiation functionalized nonwoven fabric for pollutant control.

A remarkably efficient and affordable Fe/Cu bimetallic catalyst featuring a substantial light energy utilization and compatibility with a sizable substrate was developed for Fenton-like reactions aimed at pollutant control. Specifically, a novel strategy was employed to synthesize high-density metal sites (Fe:Cu ≈ 3:1) robustly embedded on polyethylene/polyethylene terephthalate nonwoven fabric (PE/PET NWF) via radiation-induced graft polymerization (RIGP) and subsequent chemical modification, labeled as Fe/Cu-PPAO. Its high effectiveness was demonstrated by degrading 50 mg/L of tetracycline hydrochloride within 30 min in the presence of H2O2 under simulate sunlight irradiation. It was investigated that amidoxime groups regulated the optical gaps and HOMO-LUMO gaps of metal ions to enable the absorption of a broader spectrum light while the Cu2+ facilitated the transfer of electrons between the bimetal ions to achieve an improved reaction path. Furthermore, X-ray absorption fine structure (XAFS) and density functional theory (DFT) calculations further revealed its special complex state and delicate electronic structure between bimetal ions and amidoxime groups. Our study offers a new strategy to synthesize high-density bimetallic sites catalyst for environmental remediation and pushes forward insight into understanding the catalytic mechanism of bimetallic Fenton-like catalysts.

Machine learning-based prediction models for parathyroid carcinoma using pre-surgery cognitive function and clinical features.

Patients with parathyroid carcinoma (PC) are often diagnosed postoperatively, due to incomplete resection during the initial surgery, resulting in poor outcomes. The aim of our study was to investigate the pre-surgery indicators of PC and try to develop a predictive model for PC utilizing machine learning. Evaluation of pre-surgery neuropsychological function and confirmation of pathology were carried out in 133 patients with primary hyperparathyroidism in Beijing Chaoyang Hospital from December 2019 to January 2023. Patients were randomly divided into a training cohort (n = 93) and a validating cohort (n = 40). Analysis of the clinical dataset, two machine learning including the extreme gradient boosting (XGBoost) and the least absolute shrinkage and selection operator (LASSO) regression were utilized to develop the prediction model for PC. Logistic regression analysis was also conducted for comparison. Significant differences in elevated parathyroid hormone and decreased serum phosphorus in PC compared to (BP). The lower score of MMSE and MOCA was observed in PC and a cutoff of MMSE < 24 was the optimal threshold to stratify PC from BP (area under the curve AUC 0.699 vs 0.625). The predicted probability of PC by machine learning was similar to the observed probability in the test set, whereas the logistic model tended to overpredict the possibility of PC. The XGBoost model attained a higher AUC than the logistic algorithms and LASSO models. (0.835 vs 0.683 vs 0.607). Preoperative cognitive function may be a probable predictor for PC. The cognitive function-based prediction model based on the XGBoost algorithm outperformed LASSO and logistic regression, providing valuable preoperative assistance to surgeons in clinical decision-making for patients suspected PC.

PTH levels, sleep quality, and cognitive function in primary hyperparathyroidism.

BACKGROUND: Cognitive function in patients with primary hyperparathyroidism (PHPT) may be affected and be identified to have been linked to the level of parathyroid hormone (PTH). Previous studies have suggested that patients with PHPT present poor sleep quality, which might interact with cognitive decline. The purpose of this study was to determine whether sleep quality mediates the association between PTH level and cognitive function and investigate whether surgery improves sleep quality and cognition in PHPT patients. METHODS: Between June 2019 and August 2022, we recruited 146 patients diagnosed with PHPT (n = 146). We collected clinical data from medical records and evaluated sleep quality and cognition preoperatively and 2 months postoperatively by using the Pittsburgh Sleep Quality Index and Min-Mental State Examination. We examined the mediation effects of sleep disturbance and latency on correlations between PTH level and cognitive impairment by using the Bootstrap method. RESULTS: The sleep quality and cognitive function were correlated with PTH level before surgery. Sleep latency or sleep disturbance exhibited a partial mediating effect on the association between PTH level and MMSE scores in PHPT patients (p < 0.05). In PHPT patients, there was a significant decline in PTH levels and an improvement in cognitive function post-surgery compared to pre-surgery, but no significant differences in sleep quality. CONCLUSION: Sleep disturbance and sleep latency may mediate the association between PTH level and cognitive impairment in PHPT before surgery. The surgery could reduce PTH levels and improve cognition, but might not improve sleep quality in PHPT patients.

Decoding the colorectal cancer ecosystem emphasizes the cooperative role of cancer cells, TAMs and CAFsin tumor progression.

BACKGROUND: Single-cell transcription data provided unprecedented molecular information, enabling us to directly encode the ecosystem of colorectal cancer (CRC). Characterization of the diversity of epithelial cells and how they cooperate with tumor microenvironment cells (TME) to endow CRC with aggressive characteristics at single-cell resolution is critical for the understanding of tumor progression mechanism. METHODS: In this study, we comprehensively analyzed the single-cell transcription data, bulk-RNA sequencing data and pathological tissue data. In detail, cellular heterogeneity of TME and epithelial cells were analyzed by unsupervised classification and consensus nonnegative matrix factorization analysis, respectively. Functional status of epithelial clusters was annotated by CancerSEA and its crosstalk with TME cells was investigated using CellPhoneDB and correlation analysis. Findings from single-cell transcription data were further validated in bulk-RNA sequencing data and pathological tissue data. RESULTS: A distinct cellular composition was observed between tumor and normal tissues, and tumors exhibited immunosuppressive phenotypes. Regarding epithelial cells, we identified one highly invasiveQuery cluster, C4, that correlated closely with tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs). Further analysis emphasized the TAMs subclass TAM1 and CAFs subclass S5 are closely related with C4. CONCLUSIONS: In summary, our study elaborates on the cellular heterogeneity of CRC, revealing that TAMs and CAFs were critical for crosstalk network epithelial cells and TME cells. This in-depth understanding of cancer cell-TME network provided theoretical basis for the development of new drugs targeting this sophisticated network in CRC.

Metal-Organic Framework@Metal Oxide Heterostructures Induced by Electron-Beam Radiation.

Metal organic frameworks (MOFs) are a distinct family of crystalline porous materials finding extensive applications. Their synthesis often requires elevated temperature and relatively long reaction time. We report here the first case of MOF synthesis activated by high-energy (1.5 MeV) electron beam radiation from a commercially available electron-accelerator. Using ZIF-8 as a representative for demonstration, this type of synthesis can be accomplished under ambient conditions within minutes, leading to energy consumption about two orders of magnitude lower than that of the solvothermal condition. Interestingly, by controlling the absorbed dose in the synthesis, the electron beam not only activates the formation reaction of ZIF-8, but also partially etches the material during the synthesis affording a hierarchical pore architecture and highly crystalline ZnO nanoparticles on the surface of ZIF-8. This gives rise to a new strategy to obtain MOF@metal oxide heterostructures, finding utilities in photocatalytic degradation of organic dyes.

Proteomics study of Mycoplasma pneumoniae pneumonia reveals the Fc fragment of the IgG-binding protein as a serum biomarker and implicates potential therapeutic targets.

Macrolide and corticosteroid resistance has been reported in patients with Mycoplasma pneumoniae (MP) pneumonia (MPP). MP clearance is difficult to achieve through antibiotic treatment in sensitive patients with severe MPP (SMPP). SMPP in children might progress to airway remodeling and even bronchiolitis/bronchitis obliterans. Therefore, identifying serum biomarkers that indicate MPP progression and exploring new targeted drugs for SMPP treatment require urgency. In this study, serum samples were collected from patients with general MPP (GMPP) and SMPP to conduct proteomics profiling. The Fc fragment of the IgG-binding protein (FCGBP) was identified as the most promising indicator of SMPP. Biological enrichment analysis indicated uncontrolled inflammation in SMPP. ELISA results proved that the FCGBP level in patients with SMPP was substantially higher than that in patients with GMPP. Furthermore, the FCGBP levels showed a decreasing trend in patients with GMPP but the opposite trend in patients with SMPP during disease progression. Connectivity map analyses identified 25 possible targeted drugs for SMPP treatment. Among them, a mechanistic target of rapamycin kinase (mTOR) inhibitor, which is a macrolide compound and a cell proliferation inhibitor, was the most promising candidate for targeting SMPP. To our knowledge, this study was the first proteomics-based characterization of patients with SMPP and GMPP.

IOBR: Multi-Omics Immuno-Oncology Biological Research to Decode Tumor Microenvironment and Signatures.

Recent advances in next-generation sequencing (NGS) technologies have triggered the rapid accumulation of publicly available multi-omics datasets. The application of integrated omics to explore robust signatures for clinical translation is increasingly emphasized, and this is attributed to the clinical success of immune checkpoint blockades in diverse malignancies. However, effective tools for comprehensively interpreting multi-omics data are still warranted to provide increased granularity into the intrinsic mechanism of oncogenesis and immunotherapeutic sensitivity. Therefore, we developed a computational tool for effective Immuno-Oncology Biological Research (IOBR), providing a comprehensive investigation of the estimation of reported or user-built signatures, TME deconvolution, and signature construction based on multi-omics data. Notably, IOBR offers batch analyses of these signatures and their correlations with clinical phenotypes, long non-coding RNA (lncRNA) profiling, genomic characteristics, and signatures generated from single-cell RNA sequencing (scRNA-seq) data in different cancer settings. Additionally, IOBR integrates multiple existing microenvironmental deconvolution methodologies and signature construction tools for convenient comparison and selection. Collectively, IOBR is a user-friendly tool for leveraging multi-omics data to facilitate immuno-oncology exploration and to unveil tumor-immune interactions and accelerating precision immunotherapy.

Current progress and quality of radiomic studies for predicting EGFR mutation in patients with non-small cell lung cancer using PET/CT images: a systematic review.

OBJECTIVES: To assess the methodological quality of radiomic studies based on positron emission tomography/computed tomography (PET/CT) images predicting epidermal growth factor receptor (EGFR) mutation status in patients with non-small cell lung cancer (NSCLC). METHODS: We systematically searched for eligible studies in the PubMed and Web of Science datasets using the terms "radiomics", "PET/CT", "NSCLC", and "EGFR". The included studies were screened by two reviewers independently. The quality of the radiomic workflow of studies was assessed using the Radiomics Quality Score (RQS). Interclass correlation coefficient (ICC) was used to determine inter rater agreement for the RQS. An overview of the methodologies used in steps of the radiomics workflow and current results are presented. RESULTS: Six studies were included with sample sizes of 973 ranging from 115 to 248 patients. Methodologies in the radiomic workflow varied greatly. The first-order statistics were the most reproducible features. The RQS scores varied from 13.9 to 47.2%. All studies were scored below 50% due to defects on multiple segmentations, phantom study on all scanners, imaging at multiple time points, cut-off analyses, calibration statistics, prospective study, potential clinical utility, and cost-effectiveness analysis. The ICC results for majority of RQS items were excellent. The ICC for summed RQS was 0.986 [95% confidence interval (CI): 0.898-0.998]. CONCLUSIONS: The PET/CT-based radiomics signature could serve as a diagnostic indicator of EGFR mutation status in NSCLC patients. However, the current conclusions should be interpreted with care due to the suboptimal quality of the studies. Consensus for standardization of PET/CT-based radiomic workflow for EGFR mutation status in NSCLC patients is warranted to further improve research. ADVANCES IN KNOWLEDGE: Radiomics can offer clinicians better insight into the prediction of EGFR mutation status in NSCLC patients, whereas the quality of relative studies should be improved before application to the clinical setting.

Prognostic Significance of NLR About NETosis and Lymphocytes Perturbations in Localized Renal Cell Carcinoma With Tumor Thrombus.

BACKGROUND: Non-metastatic renal cell carcinoma (RCC) with tumor thrombus showed a greater tendency for developing metastases after surgery. Early identification of patients with high risk of poor prognosis is especially important to explore adjuvant treatment of improving outcomes. Neutrophil-to-lymphocyte ratio (NLR) was a systemic inflammation marker and outcome predictor in RCC, reflecting the chaos in systemic immune status in cancer as myeloid cell expansion and lymphatic cell suppression. Neutrophil extracellular traps (NET) formation (NETosis) is the process of neutrophils generating an extracellular DNA net-like structure. NETosis in tumor was demonstrated to conduce to the subsequent metastases of tumor. However, the role of NLR for systemic immune status and tumor local immune infiltration, especially for neutrophil-associated NETs, in non-metastatic RCC with thrombus remains unclear. PATIENTS AND METHODS: In our clinical cohort, we enrolled the clinical, pathologic, and preoperative laboratory parameters of 214 RCC patients with tumor thrombus who were treated surgically. The clinical endpoint was defined as cancer-specific survival (CSS). In our basic research cohort, RNA-seq, TCR-seq, and scRNA-seq data were analyzed. Patients who reached the endpoint as recurrence-free survival (RFS) were defined as the "High-risk" group. Otherwise, they were separated into the "Low-risk" group. RESULTS: In the clinical cohort, NLR≥4 was an independent risk factor for 203 localized RCC with tumor thrombus. In the basic research cohort, tumor thrombi were separated into NETosis-thrombi belonging to the "High-risk" group and non-NETosis-thrombi to the "Low-risk" group. NETs induced by tumor-derived G-CSF in tumor thrombus has a mechanistic role in unfavorable prognosis. Besides, NETs-score from single sample GSEA (ssGSEA) algorithm was an independent prognostic factor validated in the TCGA data. Apart from the neutrophils-associated NETosis, systemic immune perturbations of lymphocytes occurred in the "High-risk" group, represented with decreased TCR diversity and increasingly high proportion of CD4-positive effector memory T (Tem) cells, which indirectly represented the state of lymphopenia. CONCLUSIONS: Our findings firstly demonstrated that neutrophils-associated NETosis and systemic lymphocytes perturbations were considered as tumor progression in patients of localized RCC with tumor thrombus, which reflected NLR≥4 as an independent risk factor for patients.

Fabrication and Potential Applications of Highly Durable Superhydrophobic Polyethylene Terephthalate Fabrics Produced by In-Situ Zinc Oxide (ZnO) Nanowires Deposition and Polydimethylsiloxane (PDMS) Packaging.

Considerable attention has been devoted to the in-situ deposition of zinc oxide (ZnO) nanowires (ZnO-NWs) on the surface of organic supports, due to their very wide applications in superhydrophobicity, UV shielding, and nanogenerators. However, the poor interfacial bond strength between ZnO-NWs and its support limits their applications. Herein, we developed a facile process to grow robust ZnO-NWs on a polyethylene terephthalate (PET) fabric surface through simultaneous radiation-induced graft polymerization, hydrothermal processing, and in-situ nano-packaging; the obtained materials were denoted as PDMS@ZnO-NWs@PET. The introduction of an adhesion and stress relief layer greatly improved the attachment of the ZnO-NWs to the support, especially when the material was subjected to extreme environment conditions of external friction forces, strong acidic or alkaline solutions, UV-irradiation and even washing with detergent for a long time. The PDMS@ZnO-NWs@PET material exhibited excellent UV resistance, superhydrophobicity, and durability. The ZnO-NWs retained on the fabric surface even after 30 cycles of accelerated washing. Therefore, this process can be widely applied as a universal approach to overcome the challenges associated with growing inorganic nanowires on polymeric support surfaces.

Co2+ anchored on surface-functionalized PET non-woven fabric and used as high efficiency monoatom-like catalyst for activating Oxone in water.

Fenton-like processes have emerged as most promising techniques for generating reactive oxygen-containing radicals to deal with increasing levels of environmental pollution. Developing novel catalysts with simple manufacturing requirements, excellent activity levels, and stability remains a long-term goal in terms of practical application. So herein, a new polyethylene terephthalate (PET) non-woven fabric based composite catalyst has been fabricated, using radiation-induced graft polymerization of a functionalized group to chelate Co2+ ions as heterogeneous catalysts in peroxymonosulfate (Oxone) activation. Several impact factors, including catalyst dosage, Oxone concentration, reaction temperature, pH value, Co2+ precipitation ratio (of Co@PET at different pH values), and highly concentrated NaCl have been investigated here. Notably, Co@PET has shown the lowest activation energy of any reported catalyst, for degrading RhB by activating Oxone. Interestingly, as experimental RhB and Oxone solutions were passed through single Co@PET sheets, the RhB was decomposed into a colorless solution in the penetration process. Based on radical trapping and quenching experiments, a channel was determined to dominate RhB degradation, and furthermore, Co@PET could be re-used for RhB degradation by activating Oxone. These results showed that Co@PET effectively provided improved Fenton-like catalytic performance and stability, and was suitable for practical applications.

Immune microenvironments differ in immune characteristics and outcome of glioblastoma multiforme.

Understanding the interactions between tumors and the host immune system holds great promise to uncover biomarkers for targeted therapies, predict the prognosis of patients and guide clinical treatment. However, the immune signatures of glioblastoma multiforme (GBM) remain largely unstudied in terms of systematic analyses. We aimed to classify GBM samples according to immune-related genes and complement the existing immunotherapy system knowledge. In this study, we designed a strategy to identify 3 immune subtypes representing 3 different immune microenvironments (M1-M3) and associated with prognosis. The 3 subtypes were significantly different in terms of specific immune characteristics (immune cell subpopulations, immune responses, immune cells, and checkpoint gene interactions). In additional, copy number variations and methylation changes were identified that correlated with genes related to a worse prognosis subtype in the microenvironment. More importantly, in M3 (worst prognosis subtype) and M2 (best prognosis subtype), the interaction between immune cells and checkpoint genes was different, which had an important effect on the prognosis. Finally, we used risk scores of immune cells and checkpoint genes to evaluate the prognosis of GBM patients and validated the results with 3 independent datasets. Disordered interactions between immune cells and checkpoint genes result in a change in the immune microenvironment and affects the prognosis of patients. We propose that a better understanding of the immune microenvironment of advanced cancers may provide new insights into immunotherapy.

Identification of Distinct Immune Subtypes in Colorectal Cancer Based on the Stromal Compartment.

The tumor environment is of vital importance for the incidence and development of colorectal cancer. Increasing evidence in recent years has elaborated the vital role of the tumor environment in cancer subtype classification and patient prognosis, but a comprehensive understanding of the colorectal tumor environment that is purely dependent on the stromal compartment is lacking. To decipher the tumor environment in colorectal cancer and explore the role of its immune context in cancer classification, we performed a gene expression microarray on the stromal compartment of colorectal cancer and adjacent normal tissues. Through the integrated analysis of our data with public gene expression microarray data of stromal and epithelial colorectal cancer tissues processed through laser capture microdissection, we identified four highly connected gene modules representing the biological features of four tissue compartments by applying a weighted gene coexpression network analysis algorithm and classified colorectal cancers into three immune subtypes by adopting a nearest template prediction algorithm. A systematic analysis of the four identified modules mainly reflected the close interplay between the biological changes of intrinsic and extrinsic characteristics at the initiation of colorectal cancer. Colorectal cancers were stratified into three immune subtypes based on gene templates identified from representative gene modules of the stromal compartment: active immune, active stroma, and mixed type. These immune subtypes differed by the immune cell infiltration pattern, expression of immune checkpoint inhibitors, mutation landscape, extent of mutation burden, extent of copy number burden, prognosis and chemotherapeutic sensitivity. Further analysis indicated that activation of the NF-kB signaling pathway was the major mechanism causing the no immune infiltration milieu in the active stroma subtype and that inhibitors of the NF-kB signaling pathway could be candidate drugs for treating patients with an active stroma. Overall, these results suggest that characterizing colorectal cancer by the tumor environment is of vital importance in predicting patients' clinical outcomes and helping guide precision and personalized treatment.