BACKGROUND:N-acetyltransferase 10 (NAT10) is an RNA acetyltransferase that catalyzes N4-acetylcytidine (ac⁴C) modification and regulates mRNA stability. However, its biological function and mechanistic role in colorectal cancer (CRC) remain poorly defined. METHODS:NAT10 expression was analyzed across multiple GEO cohorts and paired CRC clinical specimens. Gain- and loss-of-function experiments were performed to assess the effects of NAT10 on CRC cell proliferation, migration, colony formation, and tumor growth in vivo. Transcriptomic correlation and enrichment analyses were used to identify NAT10-associated pathways. RIP-seq mining, NAT10-RIP-qPCR, and ac⁴C-RIP-qPCR were applied to verify downstream targets. Actinomycin D chase assays were used to evaluate mRNA stability. The functional relevance of CDK4 was examined using genetic NAT10 perturbation, Remodelin-based pharmacologic treatment, and CDK4 rescue experiments. RESULTS:NAT10 was markedly up-regulated in CRC tissues compared with normal mucosa and was maintained at high levels in malignant CRC lesions. NAT10 overexpression enhanced CRC cell proliferation, migration, and colony formation, whereas NAT10 knockout suppressed these phenotypes. In vivo, NAT10-deficient cells formed significantly smaller and slower-growing xenograft tumors, with markedly reduced tumor volume and weight compared with controls. Pathway analyses indicated strong enrichment of cell-cycle programs, particularly the G1/S transition. CDK4 was identified as a NAT10-associated ac⁴C-modified target. NAT10 depletion destabilized CDK4 mRNA, reduced CDK4-associated cell-cycle protein expression, and induced G1/S accumulation, while NAT10 overexpression produced the opposite effects. Remodelin treatment, used as a pharmacologic perturbation of NAT10-associated signaling, suppressed CDK4 expression and CRC cell growth, and CDK4 overexpression partially rescued these inhibitory effects. CONCLUSIONS:This study identifies a mechanistic NAT10-ac⁴C-CDK4 regulatory axis that stabilizes CDK4 mRNA, promotes G1/S transition, and drives CRC progression. Targeting NAT10 or its downstream CDK4 pathway represents a potential therapeutic strategy for CRC.

Triple-negative breast cancer (TNBC) remains the deadliest subtype of breast cancer owing to high metastatic potential and poor prognosis. Herein, we examined the antitumor effects of ursolic acid (UA), a pentacyclic triterpene compound, against TNBC and the underlying mechanisms. TNBC cells were exposed to a graded concentration of UA, and cell proliferation and migration were examined through CCK-8 and wound healing assays. Transcriptome data of 116 TNBC and 290 normal tissues were acquired for determining differentially expressed genes. Using the PubChem and the SwissTargetPrediction, potential UA targets were inferred. 10 pairs of human TNBC and normal tissues were gathered for examining the expression of UA targets FABP4 and PPARG. The influence of FABP4/PPARG knockdown and overexpression on the therapeutic effects of UA was then observed. UA treatment hampered proliferation and migration of TNBC cells in a concentration-based fashion. FABP4 and PPARG were determined as targets of UA. Their expression levels were gradually elevated as the increase of UA concentration. Clinically, TNBC tumor tissues displayed notable down-regulation of FABP4 and PPARG in comparison with normal tissues. UA treatment increased PPARG expression and promoted its activation, which could be effectively attenuated by FABP4 knockdown. In addition, the efficacy of UA on suppressing TNBC cell growth and migration was notably reversed and enhanced by FABP4/PPARG knockdown and overexpression, respectively. This study suggests that UA treatment increases PPARG expression through modulating FABP4, thus preventing TNBC progression, expanding the clinical application of UA and providing a theoretical basis for its usage in TNBC treatment.

Background: Transcatheter arterial chemoembolization combined with lenvatinib plus PD-1 inhibitors (triple therapy) is a promising treatment modality for uHCC. Identifying variables influencing prognosis can facilitate more personalized treatment. This study aimed to determine predictors of short-term survival (STS) and long-term survival (LTS) in patients with uHCC treated with triple therapy. Methods: This multicenter retrospective study reviewed patients with uHCC who underwent triple therapy at seven tertiary hospitals in China between June 2018 and May 2023. STS was defined as survival <12 months from the initiation of treatment, and LTS was defined as survival ≥24 months. Univariate and multivariate logistic regression analyses were performed to identify predictors of STS and LTS. Variables examined were: age, gender, hepatitis B virus infection, performance status, alpha-fetoprotein, macrovascular invasion, extrahepatic metastasis, tumor size, tumor number, total bilirubin, albumin, alanine aminotransferase, aspartate transaminase, and albumin-bilirubin grade. Findings: 289 patients were included, with the following baseline characteristics: median age 55.7 years, 88.2% male, 87.2% hepatitis B virus infection, 26.3% Barcelona Clinic Liver Cancer stage B, and 73.7% stage C. Treatment-related adverse events occurred in 88.2% of patients, with 29.8% experiencing grade 3–5 adverse events. Median overall survival was 29.2 months (95% confidence interval, 23.1–NA). Sixty-five (22.5%) patients had STS and 89 (30.8%) had LTS. The independent predictors of STS were alpha-fetoprotein level ≥400 ng/mL [odds ratio (OR), 2.04; p = 0.033], extrahepatic metastasis (OR, 3.83; p < 0.001), and maximum tumor size ≥5 cm (OR, 3.79; p = 0.039). Absence of macrovascular invasion (OR, 1.99; p = 0.019), absence of extrahepatic metastasis (OR, 3.01; p = 0.008), and maximum tumor size <5 cm (OR, 2.85; p = 0.002) were independent predictors of LTS. Interpretation: Higher alpha-fetoprotein levels, extrahepatic metastasis, and larger tumor size were predictors of STS, while no macrovascular invasion, no extrahepatic metastasis, and smaller tumor size predicted LTS in patients with uHCC treated with triple therapy. These findings may help guide treatment decisions in uHCC. Funding: This study was funded by the Medical Innovation Project of Health and Family Planning Commission of Fujian Province (Grant number: 2022CXA002).

Introduction: Accurately predicting the outcomes of conversion therapy among patients with initially unresectable hepatocellular carcinoma (uHCC) remains a challenge. Clinical complete response (cCR) has been proposed as a predictor of prognosis. However, information on its prognostic value in these patients is limited. We aimed to explore the prognostic value of cCR in patients with uHCC following conversion therapy and identify predictors of cCR. Methods: We included 241 patients with uHCC who underwent transcatheter arterial chemoembolization combined with lenvatinib and PD-1 inhibitors (triple therapy) as first-line treatment. The prognostic value of cCR, predictive factors of cCR, and the relationship between cCR and pathological complete response (pCR) were analyzed. Results: The cCR rate of the 241 patients included was 17.4%. Patients with cCR showed better overall survival (OS) (p < 0.001) and progression-free survival (PFS) (p < 0.001) than those without. cCR was an independent risk factor for OS (hazard ratio [HR]: 0.11, 95% confidence interval [CI]: 0.03–0.42, p = 0.001) and PFS (HR: 0.29, 95% CI: 0.15–0.56, p < 0.001). Serum α-fetoprotein levels ≥400 ng/mL (odds ratio [OR]: 0.47, 95% CI: 0.22–0.95, p = 0.040) and extrahepatic metastasis (OR: 0.13, 95% CI: 0.01–0.62, p = 0.046) were independent negative predictors of cCR. A total of 107 patients (44.4%) underwent conversion surgery. Among these patients, cCR was associated with better OS (p =0.009) and recurrence-free survival (p = 0.007). cCR was significantly correlated with pCR (Φ = 0.61, p < 0.001). Albumin levels ≥35 g/L (OR: 0.12, 95% CI: 0.02–0.69, p = 0.018) and cCR (OR: 30.32, 95% CI: 9.19–128.00, p < 0.001) were independent predictors of pCR. Conclusion: cCR after triple therapy has an excellent long-term survival advantage and is significantly related to pCR. cCR may be a surrogate marker for predicting prognosis and pCR in patients with uHCC receiving triple therapy.

The incidence of thyroid carcinoma (TC) has exhibited a rapid increase in recent years. A proportion of TCs exhibit aggressive behavior. The present study aimed to investigate the potential role of hypoxia‑hypoxia inducible factor 1 subunit α (HIF‑1α)‑periostin axis in the progression of TC. The upregulation of periostin and HIF‑1α expression levels was detected in 95 clinical TC tissues as compared with normal thyroid tissues. Hypoxia promoted the viability and invasion of TC cells and this effect was inhibited by the downregulation of periostin. Hypoxia also induced the Warburg effect in TC and this effect was inhibited by the silencing of periostin. Further investigations revealed that hypoxia activated HIF‑1α, which in turn regulated the expression of periostin. Immunoprecipitation and dual luciferase reporter assays demonstrated that HIF‑1α upregulated the expression of periostin by binding to the promoter of periostin. On the whole, these findings suggest the existence of a hypoxia‑HIF‑1α‑periostin axis in TC and indicate the role of this axis in the progression of TC.

Oxidative stress-responsive kinase 1 (OSR1) plays a critical role in multiple carcinogenic signal pathways, and its overexpression has been found in various types of cancer; however, the pathophysiological role of OSR1 in breast cancer has not been evaluated. This study aims to elaborate on the role of OSR1 in breast cancer metastasis and the specific regulatory mechanism. Our results showed that OSR1 mRNA and protein were upregulated in both human breast cancer samples and cell lines. Moreover, phosphorylated OSR1 (p-OSR1) was an independent poor prognostic indicator in patients with breast cancer. OSR1 upregulation induced epithelial-to-mesenchymal transition (EMT) in normal and malignant mammary epithelial cells with the increasing metastatic capacity. In contrast, deleting OSR1 in aggressive breast cancer cells inhibited these phenotypes. OSR1 is the critical activator for transcription factors of EMT. Mechanistically, we found that OSR1 can directly interact and phosphorylate the linker region of Smad2 at Thr220 and Smad3 at Thr179. Phosphorylated Smad2/3 translocated into the nucleus to enhance transforming growth factor-β1 (TGF-β1) autocrine signalling and increase the transcription of EMT regulators. Importantly, interruption of the OSR1-Smad2/3-TGF-β1 signalling axis elicited a robust anti-EMT and anti-metastatic effect in vitro and in vivo. Taken together, we conclude that OSR1-mediated Smad2/3-TGF-β1 signalling promotes EMT and metastasis representing a promising therapeutic target in breast cancer treatment.

Background Trastuzumab plus chemotherapy remains the standard first-line treatment strategy for HER2-positive gastric cancer (GC). Trastuzumab resistance, on the other hand, remains a significant issue. There are a few effective anti-HER2 agents for patients who develop resistance to trastuzumab. Case Presentation A 49-year-old female was diagnosed with stage IV GC with liver and lung metastasis in July 2017. She underwent gastrostomy, and the immunohistochemistry (IHC) result of postoperative tissue demonstrated HER2 (3+). She received first-line treatment of trastuzumab (440 mg), oxaliplatin (200 mg), and S-1 (40 mg). After treatment for 6 months, the patient achieved complete response (CR) with PFS up to 21 months. After progression, she subsequently received trastuzumab (440 mg) plus oxaliplatin (200 mg) as second-line treatment. However, the patient developed resistance to trastuzumab after 12 months of treatment. She started to receive third-line treatment of irinotecan (200 mg d1) and capecitabine (60 mg bid) plus pyrotinib (400 mg/day). After 2 months of treatment, the tumor is evaluated as partial response with PFS of 12 months. Conclusions We presented a patient with HER2-positive GC who benefited from the pyrotinib-based treatment after two lines of trastuzumab-based therapies failed. Further research is required to validate such conclusions.

Introduction Endothelial cells play important roles in neurodegenerative diseases caused by diabetes, therefore, we aimed at investigating the mechanisms through which endothelial cells are involved in diabetes development. Methods Single cell analysis was performed to identify the major endothelial cell subtypes in cardiovascular tissues that are involved in diabetes development. A cell-cell communication approach was then used to identify ligand-receptor interaction pairs between these cell types. Differential expression analysis between the two experimental groups [standard chow diet group and diabetogenic diet with cholesterol (DDC) group] was used to identify diabetes-related differentially expressed genes (DEGs). The upregulated genes were used to identify candidate ligands or receptors, as well as the corresponding cell types. Cell trajectory inference was performed to identify the stage of cell development and changes in expression of candidate ligands or receptors during cell development. Gene set enrichment analysis (GSEA) was conducted to investigate the biological functions of genes of purpose. Finally, molecular dynamics simulations (MDSs) were used to predict potential drugs with the ability to target the proteins of purpose. Results Seven cell types, including five endothelial cell subtypes (EC_1, EC_2, EC_3, EC_4, and EC_EndMT), were identified from endothelial cell-enriched single cell samples from the heart and aorta of mice. Cell-cell communication analysis revealed the potential ligand-receptor interactions between these cell types while five important ligand-receptor-associated genes, including Fn1, Vcam1, Fbn1, Col4a1, and Col4a2, were established by differential expression analysis. Among them, Vcam1 is mainly expressed in EC_EndMT and is involved in interactions between EC_EndMT and other cells. Cell trajectory extrapolation analysis revealed a shift from EC_2/EC_4 to EC_EndMT and a shift from EC_EndMT to EC_3/EC_1 during the progression of diabetes. GSEA analysis revealed that upregulation of VCAM1 may have inhibitory effects on cell growth and energy metabolism. Conclusion EC_EndMT subtypes have a complex role in neurodegenerative diseases caused by diabetes. Through mechanisms involved in cell-cell communication, Vcam1 may play an important role in dysregulation of biological functions of EC_ EndMT. Molecular docking results of the quercetin-VCAM1 complex suggest that quercetin may be an effective drug for targeting this protein.

This study sought to perform integrative analysis of the immune/methylation/autophagy landscape on breast cancer prognosis and single-cell genotypes. Breast Cancer Recurrence Risk Score (BCRRS) and Breast Cancer Prognostic Risk Score (BCPRS) were determined based on 6 prognostic IMAAGs obtained from the TCGA-BRCA cohort. BCRRS and BCPRS, respectively, were used to construct a risk prediction model of overall survival and progression-free survival. Predictive capacity of the model was evaluated using clinical data. Analysis showed that BCRRS is associated with a high risk of stroke. In addition, PPI and drug-ceRNA networks based on differences in BCPRS were constructed. Single cells were genotyped through integrated scRNA-seq of the TNBC samples based on clustering results of BCPRS-related genes. The findings of this study show the potential regulatory effects of IMAAGs on breast cancer tumor microenvironment. High AUCs of 0.856 and 0.842 were obtained for the OS and PFS prognostic models, respectively. scRNA-seq analysis showed high expression levels of adipocytes and adipose tissue macrophages (ATMs) in high BCPRS clusters. Moreover, analysis of ligand-receptor interactions and potential regulatory mechanisms were performed. The LINC00276&MALAT1/miR-206/FZD4-Wnt7b pathway was also identified which may be useful in future research on targets against breast cancer metastasis and recurrence. Neural network-based deep learning models using BCPRS-related genes showed that these genes can be used to map the tumor microenvironment. In summary, analysis of IMAAGs, BCPRS, and BCRRS provides information on the breast cancer microenvironment at both the macro- and microlevels and provides a basis for development of personalized treatment therapy.

Abstract Due to the poor prognosis for hepatocellular carcinoma (HCC) presently, a systemic analysis supported by the multi-omics data is extremely necessary to search for gene markers for the clinical prognostic prediction of HCC. The data on RNA-seq, single nucleotide polymorphism (SNP), and copy number variation (CNV), etc. were downloaded from TCGA, leading to a final of 367 samples, which were divided into training set and testing set randomly. In the training set, both prognosis-related genes and those with SNP or CNV were screened, which were incorporated for feature selection using the random forest method. The testing and GEO verification sets (N = 265) were used to verify the constructed gene-related prognosis model. qPCR was used to detect the expression of 5 genes in clinical specimens. After including genomic variant and prognosis-related genes, we got 78 candidate genes and 5 feature genes (CISH, LHPP, MGMT, PDRG1, and LCAT) eventually through random forest feature selection. The 5-gene signature is an independent prognostic risk factor for HCC patients. In addition, the signature shows good predicting performance and clinical practicality in train- ing set, testing set and external verification set. The results of qPCR based on clinical samples showed that the expression of PDRG1 was increased in colon cancer tissues and the expression of CISH, LHPP, MGMT and LCAT were decreased in colon cancer tissues. We identify the ability of 5-gene signature to serve as an innovative marker of survival prediction for patients with HCC.

YEATS domain-containing protein 4 (YEATS4) is implicated in several oncogenic signaling pathways, and its expression is involved in various types of cancer; regardless, the pathophysiologic effects of YEATS4 on breast cancer remain unclear. This study finds that YEATS4 is increasingly expressed with breast cancer progression, and its expression is related to poor outcome and distant metastasis. YEATS4 overexpression in breast cancer cells strengthens their malignant characteristics in vitro and in vivo, particularly inducing epithelial-to-mesenchymal transition (EMT) and consequently, metastatic capability in breast cancer cells. By contrast, deleting YEATS4 in breast cancer cells with high-grade malignancy reduced these characteristics. With regard to the molecular mechanism, YEATS4 mediates histone H3K27ac at specific sites of the ZEB1 promoter to regulate its expression at the transcription level. Depleting ZEB1 blocks YEATS4-induced EMT, migration, invasion, and metastasis. YEATS4 expression is also positively correlated with ZEB1 expression in patients with breast cancer. Co-expression of YEATS4 and ZEB1 correlates with the shortest distant metastasis-free period. Taken together, our data reveal the critical role of YEATS4 in the progression and metastasis of breast cancer, as well as support YEATS4 as a potential therapeutic target and prognostic biomarker for breast cancer.

Tryptophan 2,3-dioxygenase (TDO2), an enzyme involved in tryptophan (Trp) metabolism has been linked with some malignant traits of various cancers. Kyn, the main product of Trp metabolism pathway catalyzed by TDO2 and indoleamine 2,3-dioxygenase (IDO) in tumor cells, was also demonstrated to activate aryl hydrocarbon receptor (AhR), which may regulate cancer growth and invasion in some malignancies. However, whether TDO2 participates in the metastasis and invasion of HCC has not been explored before. The underlying mechanism played by TDO2 in this process still requires further investigation. Here, we demonstrated that overexpression of TDO2 correlates with advanced stage or malignant traits in HCC patients. Knockdown or inhibition of TDO2 suppressed the migration and invasion of HCC cells in vitro and in vivo . Epithelial to mesenchymal transition (EMT) is an essential program happened in the initial phase of cancer metastasis. We found that in HCC cells, TDO2 promoted the EMT process evidenced by altered levels of biomarkers for EMT. Mechanically, TDO2 regulated the Kyn production in HCC cell via activated aryl hydrocarbon receptor (AhR). Together, these results indicate that TDO2 promotes the EMT of hepatocellular carcinoma through activating Kyn-AhR pathway, thereby participating in the metastasis and invasion of HCC.

1Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, People’s Republic of China; 2Department of General Surgery, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai, People’s Republic of China; 3Division of Pathology, Tulane National Primate Research Center, Health Sciences Campus, Covington, LA 70433, USA

Oxidative stress-responsive kinase 1 (OSR1) plays a crucial role in regulating diverse cellular pathophysiologic functions, including ion homeostasis, development, differentiation, angiogenesis, invasive migration, and metastasis. Regardless, the clinical significance of OSR1 in breast cancer is scarce. The current study was conducted to evaluate the effect of OSR1 on the prognosis of patients with breast cancer with a long-term follow-up. OSR1 expression in formalin-fixed and paraffin-embedded tissue specimens was analyzed. These specimens were collected from 551 evaluable breast cancer cases by immunohistochemistry (IHC). OSR1 expression was dichotomized based on the H-score in IHC. The effects of OSR1 levels on the clinicopathological attributes and survival prediction in patients with breast cancer were explored. Among 551 specimens, 183 (33.2%) exhibited high expression of OSR1 in tumor cells. High OSR1 levels were markedly correlated with histologic grade (P = 0.035), ER (P < 0.001) and PgR (P = 0.043) expression, lymph node involvement (P < 0.001), TNM stage (P < 0.001), and axillary surgery procedures (P = 0.003). Univariate analysis results indicate that patients with high OSR1 expression had significantly poor overall survival (P < 0.001), distant disease-free survival (P < 0.001), and breast cancer-specific survival (P < 0.001). Multivariable Cox regression analyses suggest that OSR1 expression was an independent predictive marker of poor prognosis and lymph node metastasis (HR 3.224, 95% CI 1.182–8.702, P = 0.023) in patients with breast cancer. Our findings indicate that OSR1 is a significantly independent prognosis index for patients with breast cancer with respect to distant disease-free survival, overall survival, and breast cancer-specific survival. High OSR1 expression caused an increase in deaths specifically attributed to breast cancer and was related to increased lymph node metastasis. However, the precise cellular mechanisms for OSR1 in breast cancer require further research.

Background: Hepatocellular carcinoma (HCC) recurrence appears commonly after liver transplantation (LT), and it severely affected the long-term survival of patients. Previous studies have proved that Rap1A is involved in hepatocarcinogenesis and metastasis, and demonstrated the significant association between Rap1A gene rs494453 polymorphism and HCC. However, the relationship between Rap1A rs494453 polymorphism and HCC recurrence after LT remained unclear. Methods: A total of 74 HCC patients who underwent LT from July 2005 to June 2015 was analyzed. The genotypes of both donors and recipients had been confirmed as Rap1A rs494453. The independent risk factors that associated with HCC recurrence were investigated with univariate and multivariate logistic regression analysis. The recurrence-free (RFS) and overall survival (OS) were calculated with Cox regression analysis. The Rap1A rs494453 genotype frequencies were determined using the Χ² test and the minor allele frequencies (MAFs) of Rap1A rs494453 genotypes were calculated by Hardy-Weinberg equilibrium. Results: We found that the donor Rap1A rs494453 polymorphism was profoundly associated with HCC recurrence after LT. Moreover, the Milan criteria, microvascular invasion and donor Rap1A rs494453 genotype were proved to be independent risk factors for HCC recurrence. Patients with donor AG/GG genotypes had a distinct lower RFS and OS than AA genotype. The TNM stage, Milan criteria, microvascular invasion, and donor Rap1A rs494453 genotype were independent factors for the RFS of LT patients. Conclusions: Donor Rap1A rs494453 is a potential predictive marker for HCC recurrence risk after LT.

Purpose: Tryptophan 2,3-dioxygenase (TDO), encoded by the gene TDO2, is an enzyme that catalyses the first and rate-limiting step of tryptophan (Try) degradation in the kynurenine (Kyn) pathway in the liver. Recently, TDO has been demonstrated to be expressed in various human tumours, especially hepatocellular carcinoma (HCC). However, the role of TDO in HCC is still not very clear. Here, we studied the role of TDO in HCC. Methods: We demonstrated that TDO is overexpressed in human HCC tissues and is significantly correlated with malignant phenotype characteristics, including tumour size, tumour differentiation, vascular invasion, etc. Kaplan-Meier analysis showed a poor overall survival rate in patients with TDO-overexpressing tumours. In addition, the effects of TDO on HCC tumour growth and metastasis were detected both in vivo and in vitro. TDO overexpression facilitated HCC cell growth, invasion and migration. Conclusion: Our results suggest that TDO positively regulates HCC proliferation and invasion and acts as a new prognostic biomarker of HCC.

Background Clinical prediction of breast cancer prognosis relies on both clinical-pathological features and biological markers. Many studies have revealed that tumor cytotoxic T lymphocyte antigen 4 (CTLA4) expression may present prognostic predicting value in cancers. We intended to explore the prognostic value of significant clinicopathological parameters and CTLA4 for predicting survival of patients with breast cancer. Methods A total of 229 breast cancer patients who had radical surgery treatment between Sep 2009 and April 2011 were enrolled in this study. Immunohistochemical staining was performed to evaluate CTLA4 grade and Ki-67 index in breast cancer tissue. Univariate and multivariate logistic analysis, Kaplan-Meier survival analysis and ROC curve were used to explore the association between CTLA4 or clinicopathological parameters and disease-free survival (DFS). A nomogram was constructed based on the regression model to predict DFS of patients with breast cancer. Results CTLA4 grade (OR 1.730, 95% CI: 1.213-2.468, P=0.002), Ki-67 (OR 1.449, 95% CI: 1.069-1.964, P=0.017) and N stage (lymph node metastasis) (OR 2.268, 95% CI: 1.588-3.303, P=0.000) showed significantly association with DFS of breast cancer patients. All these factors were independent predictors for poor survival, as patients with stage N2-3 tumors, high CTLA4 grade and Ki-67 index showed low survival probability (P<0.01). The conjunction of these factors exhibited good discrimination value (AUC 0.815, 95% CI: 0.749-0.882, P=0.000). Nomogram performed based on CTLA4 grade, Ki-67 index and N stage provided an efficient method to predict DFS of patients with breast cancer. Conclusions The high expression of CTLA4 and Ki-67 together with lymph node metastasis in breast cancer are independent risk factors that affect the prognosis of breast cancer patients. They have the potentiality to be utilized conjunctively as predictor in clinical practice.

•DWI has moderately high performance in the discrimination between malignant and benign renal lesions.•Patient source, imaging protocols and reference standard positively influence diagnostic performance.•High-quality prospective studies are still needed to explore optimal imaging parameters and diagnostic threshold values.