Clinicopathological characteristics and prognosis of Epstein-Barr virus-associated gastric cancer.

OBJECTIVE: Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) is a distinct molecular subtype of gastric cancer (GC). At present, the clinical characteristics and prognostic implications of EBV infection and the potential clinical benefits of immune checkpoint blockade in GC remain to be clarified. Hence, this study was designed to analyze the clinical and pathological characteristics of GC patients with varying EBV infection states and compare their overall survival (OS). METHODS: A retrospective study was performed on 1031 consecutive GC patients who underwent gastrectomy at the Affiliated Hospital of Xuzhou Medical University from February 2018 to November 2022. EBV-encoded RNA (EBER) in situ hybridization (ISH) was used for EBV assessment, and immunohistochemical staining was used for evaluation of human epidermal growth factor receptor 2 (HER2), programmed death ligand 1 (PD-L1), and Ki67 expression. EBVaGC was defined as tumors with EBV positivity. In addition, EBV-negative GC (EBVnGC) patients were matched with EBVaGC patients based on seven clinicopathological parameters (age, gender, anatomic subsite, tumor size, Lauren classification, degree of differentiation, and tumor-node-metastasis [TNM] stage). The correlations of clinical features with HER2, PD-L1, and Ki67 expression were evaluated statistically. The survival of patients was assessed through medical records, telephone, or WeChat communication, and prognostic analysis was performed using the logrank test as well as univariable and multivariable regression analysis. RESULTS: Out of 1031 GC patients tested, 35 (3.4%) were diagnosed with EBVaGC. Notably, the EBVaGC group exhibited a distinct predominance of males and younger patients, significantly higher Ki67 and PD-L1 expression levels, and a lower prevalence of pericancerous nerve invasion than the EBVnGC group (P < 0.01). In the 35 EBVaGC cases, Ki67 expression was negatively correlated with age (P < 0.05), suggesting that a younger onset age was associated with higher Ki67 expression. In addition, PD-L1 expression was correlated with the degree of differentiation, T-stage, and clinical stage of the patient. Furthermore, PD-L1 expression was elevated in tumors with lower differentiation or at later stages (P < 0.05). Using univariate analysis, Ki67, PD-L1, and clinical stage were identified as significant factors influencing the overall survival (OS) of EBVaGC patients (P < 0.05). Moreover, multivariate survival analysis revealed that clinical stage and Ki67 expression were independent risk factors for the OS of the patients (P < 0.05), and the three-year OS rate of EBVaGC patients was 64.2%. CONCLUSION: EBV-ISH is a practical and valuable method to identify EBVaGC. Owing to its unique etiological, pathological, and clinical characteristics, patients with EBVaGC might benefit from immune checkpoint blockade therapy.

Clinicopathological features, psychological status, and prognosis of 33 patients with occult breast cancer.

BACKGROUND: Occult breast cancer (OBC) has traditionally been considered to be a carcinoma of unknown primary origin with a favorable prognosis and can be treated as stage II-III breast cancer. Due to the small number of cases and limited clinical ex-perience, treatments vary greatly around the world and no standardized treat-ment has yet been established. AIM: To investigate the clinicopathological features, psychological status and prog-nostic features of patients with OBC. METHODS: The clinicopathological data of 33 OBC patients diagnosed and treated in the Affiliated Hospital of Xuzhou Medical University and Xuzhou Central Hospital from November 2015 to November 2022 were retrospectively analyzed. The psychological status of OBC patients was evaluated by the Self-rating Anxiety Scale and Self-rating Depression Scale. Patients' emotions, stress perception and psychological resilience were evaluated by the Positive and Negative Affect Schedule, the Chinese Perceived Stress Scale, and the Connor-Davidson Resilience Scale (CD-RISC), respectively. Patient survival was calculated using the Kaplan-Meier method, and survival curves were plotted for analysis with the log-rank test. Univariate and multivariate survival analyses were performed using the Cox regression model. RESULTS: The 33 OBC patients included 32 females and 1 male. Of the 33 patients, 30 (91%) had axillary tumors, 3 (9%) had a neck mass as the primary symptom; 18 (54.5%) had estrogen receptor-positive tumors, 17 (51.5%) had progesterone receptor-positive tumors, and 18 (54.5%) had Her-2-positive tumors; 24 (72.7%) received surgical treatment, including 18 patients who underwent modified radical mastectomy, 1 patient who underwent breast-conserving surgery plus axillary lymph node dissection (ALND), and 5 patients who underwent ALND alone; 12 patients received preoperative neoadjuvant therapy. All 30 patients developed anxiety and depression, with low positive affect scores and high negative affect scores, accompanied by a high stress level and poor psychological resilience. There were no differences in the psychological status of patients according to age, body mass index, or menopausal status. The overall survival and disease-free survival (DFS) of all the patients were 83.3% and 55.7%, respectively. Univariate analysis demonstrated that the initial tumor site (P = 0.021) and node stage (P = 0.020) were factors that may affect patient prognosis. The 5-year DFS rate of OBC patients who received radiotherapy was greater (P < 0.001), while the use of different surgical methods (P = 0.687) had no statistically significant effect on patient outcomes. Multivariate analysis revealed that radiotherapy (P = 0.031) was an independent prognostic factor. Receiving radiotherapy had a significant effect on the CD-RISC score (P = 0.02). CONCLUSION: OBC is a rare breast disease whose diagnosis and treatment are currently controversial. There was no significant difference in the efficacy of other less invasive surgical procedures compared to those of modified radical mastectomy. In addition, radiotherapy can significantly improve patient outcomes. We should pay attention to the psychological state of patients while they receive antitumor therapy.

The prognostic value of the tertiary lymphoid structure in gastrointestinal cancers.

Background: Numerous studies and research papers have provided evidence suggesting that tertiary lymphoid structures (TLS) play a crucial role in combating and suppressing tumor growth and progression. Despite the wealth of information on the significance of TLS in various types of cancer, their prognostic value in gastrointestinal (GI) cancers remains uncertain. Therefore, this meta-analysis investigated the prognostic value of TLS in GI cancers. Methods: We searched Web of science, Pubmed, Embase and Cochrane Library for studies that met the requirements as of May 1, 2023, and the hazard ratio (HR) and the corresponding 95% confidence interval (CI) were included in the analysis. The bioinformatics analysis results based on the TCGA database are used to supplement our research. Results: The meta-analysis included 32 studies involving 5778 patients. The results of comprehensive analysis showed that TLS-High is associated with prolonged OS (HR=0.525,95%CI:0.447-0.616 (P < 0.001), RFS (HR=0.546,95%CI:0.461-0.647, P < 0.001), DFS (HR=0.519,95%CI:0.417-0.646, P < 0.001) and PFS (HR=0.588,95%CI:0.406-0.852, P=0.005) in GI cancer. Among the patients who received immunotherapy, TLS-High is associated with significantly prolonged OS (HR=0.475, 95%CI:0.282-0.799, P=0.005) and PFS(HR=0.576, 95%CI:0.381-0.871, P=0.009). It is worth noting that subgroup analysis showed that there was no significant relationship between TLS and OS(HR=0.775, 95%CI:0.570-1.053,P=0.103) in CRC. And when Present is used as the cut-off criteria of TLS, there is no significant correlation between TLS and OS (HR=0.850, 95%CI:0.721-1.002, P=0.053)in HCC. Conclusion: TLS is a significant predictor of the prognosis of GI cancers and has the potential to become a prognostic biomarker of immunotherapy-related patients. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier CRD42023443562.

Safety and Efficacy of TACE + Lenvatinib in Treating Advanced Hepatocellular Carcinoma: A Systematic Review and Meta- analysis.

BACKGROUND AND AIMS: To compare the efficacy and safety of transarterial chemoembolization (TACE) + lenvatinib (TACE+L) versus lenvatinib (L) monotherapy in the treatment of advanced hepatocellular carcinoma by a meta-analysis. METHODS: PubMed, Embase, the Cochrane Library, CNKI, VIP e-Journals Database, and Wanfang Data were systematically searched to collate literature comparing TACE+L with L alone for the treatment of advanced liver cancer. The literature search, quality assessment, and data extraction were performed independently by two reviewers. The Stata 16 software package was used to process and analyze the data. We assessed heterogeneity using both I2 and the p-value, performed a publication bias assessment, and conducted a sensitivity analysis. RESULTS: Five studies were finally included, including one randomized controlled study and four retrospective studies; these involved a total of 1,167 patients, including 523 patients in the TACE+L combination group and 644 patients in the L monotherapy group. In this meta-analysis, the TACE+L group showed a significantly better objective response rate (ORR) (OR=2.54, 95%CI: 1.34 - 4.80) and disease control rate (DCR) compared to the L monotherapy group (OR=2.68, 95%CI: 1.75 - 4.08). The combined group had significantly improved progression-free survival (PFS) (HR=0.47, 95%CI: 0.40 - 0.56) and overall survival (OS) (HR=0.48, 95%CI: 0.39-0.59). In addition, there was no significant difference found in the overall adverse events of any grade between the two groups (OR=1.13, 95%CI: 0.99 - 1.29). CONCLUSIONS: Compared to L alone, TACE+L treatment resulted in better tumor response, better long-term survival, and was accompanied by controllable adverse events.

Risk prediction of bronchopulmonary dysplasia in preterm infants by the nomogram model.

Backgrounds and Aims: Bronchopulmonary dysplasia (BPD) has serious immediate and long-term sequelae as well as morbidity and mortality. The objective of this study is to develop a predictive model of BPD for premature infants using clinical maternal and neonatal parameters. Methods: This single-center retrospective study enrolled 237 cases of premature infants with gestational age less than 32 weeks. The research collected demographic, clinical and laboratory parameters. Univariate logistic regression analysis was carried out to screen the potential risk factors of BPD. Multivariate and LASSO logistic regression analysis was performed to further select variables for the establishment of nomogram models. The discrimination of the model was assessed by C-index. The Hosmer-Lemeshow test was used to assess the calibration of the model. Results: Multivariate analysis identified maternal age, delivery option, neonatal weight and age, invasive ventilation, and hemoglobin as risk predictors. LASSO analysis selected delivery option, neonatal weight and age, invasive ventilation, hemoglobin and albumin as the risk predictors. Both multivariate (AUC = 0.9051; HL P = 0.6920; C-index = 0.910) and LASSO (AUC = 0.8935; HL P = 0.7796; C-index = 0.899) - based nomograms exhibited ideal discrimination and calibration as confirmed by validation dataset. Conclusions: The probability of BPD in a premature infant could be effectively predicted by the nomogram model based on the clinical maternal and neonatal parameters. However, the model required external validation using larger samples from multiple medical centers.

Long noncoding RNA Pvt1 promotes the proliferation and migration of Schwann cells by sponging microRNA-214 and targeting c-Jun following peripheral nerve injury.

Research has shown that long-chain noncoding RNAs (lncRNAs) are involved in the regulation of a variety of biological processes, including peripheral nerve regeneration, in part by acting as competing endogenous RNAs. c-Jun plays a key role in the repair of peripheral nerve injury. However, the precise underlying mechanism of c-Jun remains unclear. In this study, we performed microarray and bioinformatics analysis of mouse crush-injured sciatic nerves and found that the lncRNA Pvt1 was overexpressed in Schwann cells after peripheral nerve injury. Mechanistic studies revealed that Pvt1 increased c-Jun expression through sponging miRNA-214. We overexpressed Pvt1 in Schwann cells cultured in vitro and found that the proliferation and migration of Schwann cells were enhanced, and overexpression of miRNA-214 counteracted the effects of Pvt1 overexpression on Schwann cell proliferation and migration. We conducted in vivo analyses and injected Schwann cells overexpressing Pvt1 into injured sciatic nerves of mice. Schwann cells overexpressing Pvt1 enhanced the regeneration of injured sciatic nerves following peripheral nerve injury and the locomotor function of mice was improved. Our findings reveal the role of lncRNAs in the repair of peripheral nerve injury and highlight lncRNA Pvt1 as a novel potential treatment target for peripheral nerve injury.

MiR-140-3p Ameliorates The Inflammatory Response of Airway Smooth Muscle Cells by Targeting HMGB1 to Regulate The JAK2/STAT3 Signaling Pathway.

OBJECTIVE: The growth and migration of airway smooth muscle cells (ASMCs) are dysregulated in asthma. MicroRNAs (miRNAs) are associated with the pathogenesis of many diseases including asthma. Instead, the function of miR-140- 3pin ASMCs' dysregulation in asthma remains inconclusive. This study aimed to explore the role and mechanism of miR-140-3p in ASMCs' dysregulation. MATERIALS AND METHODS: In this experimental study, ASMCs were stimulated with platelet-derived growth factor (PDGF)- BB to construct an asthma cell model in vitro. MiR-140-3p expression level in the plasma of 50 asthmatic patients and 50 healthy volunteers was measured with quantitative real-time polymerase chain reaction (qRT-PCR). Besides, the enzyme-linked immunosorbent assay (ELISA) was applied to detect the contents of interleukin (IL) -1ß, IL-6, and tumor necrosis factor-α (TNF-α) in the cell culture supernatant of ASMCs. Additionally, CCK-8 and transwell assays were adopted to probe the multiplication and migration of ASMCs. In addition, the western blot was employed to examine HMGB1, JAK2, and STAT3 protein expressions in ASMCs after miR-140-3p and HMGB1 were selectively regulated. RESULTS: miR-140-3p expression was declined in asthmatic patients' plasma and ASMCs stimulated by PDGF-BB. Upregulating miR-140-3p suppressed the viability and migration of the cells and alleviated the inflammatory response while inhibiting miR-140-3p showed opposite effects. Additionally, HMGB1 was testified as the target of miR-140-3p. HMGB1 overexpression could reverse the impact of miR-140-3p upregulation on the inflammatory response of ASMCs stimulated by PDGF-BB. MiR-140-3p could repress the activation of JAK2/STAT3 via suppressing HMGB1. CONCLUSION: In ASMCs, miR-140-3p can inhibit the JAK2/STAT3 signaling pathway by targeting HMGB1, thus ameliorating airway inflammation and remodeling in the pathogenesis of asthma.

The emerging roles of TRIM21 in coordinating cancer metabolism, immunity and cancer treatment.

Tripartite motif containing-21 (TRIM21), an E3 ubiquitin ligase, was initially found to be involved in antiviral responses and autoimmune diseases. Recently studies have reported that TRIM21 plays a dual role in cancer promoting and suppressing in the occurrence and development of various cancers. Despite the fact that TRIM21 has effects on multiple metabolic processes, inflammatory responses and the efficacy of tumor therapy, there has been no systematic review of these topics. Herein, we discuss the emerging role and function of TRIM21 in cancer metabolism, immunity, especially the immune response to inflammation associated with tumorigenesis, and also the cancer treatment, hoping to shine a light on the great potential of targeting TRIM21 as a therapeutic target.

Breast and cervical cancer screening adherence in Jiangsu, China: An ecological perspective.

Background: High screening coverage can effectively reduce the mortality in breast and cervical cancer. Further research on extending the coverage of breast and cervical cancer screening in China is required. This study explored factors influencing women's "two-cancer" screening service utilization using an ecological approach. Methods: Data were obtained from the National Health Services Survey (NHSS) conducted in 2018 in Jiangsu, China. A total of 3,500 women aged 18-64 years were included in the analysis. Chi-squared test, hierarchical multiple logistic regression analysis, and binary logistic regression analysis were performed. Results: In total, 44.1% of the women had been screened for breast cancer (BC) and 40.9% for cervical cancer (CC). Breast cancer screening (BCS) and cervical cancer screening (CCS) differed significantly in the following common categories: age, gestational experiences, chronic disease status, body mass index (BMI), exercise, health checkup, marital status, number of children, employment, education, family doctors, and health records. In the results of hierarchical multiple logistic regression analysis, the explanatory power of the final model was 37.5% and the area under the receiver operating characteristic curve was 0.812. The results showed that being in the age group of 35-64 years, having gestational experiences, having chronic diseases, exercising, having a health checkup, being married, having children, and being employed were statistically significant positive predictors of "two-cancer" screening adherence. The household size was a barrier. For BCS, obesity was also a negative factor, and a higher overall self-related health status was a positive factor. Being married and living in households of three or more families were not predictors. For CCS, having health records was also positively significant, while having chronic disease did not influence adherence. Conclusion: The findings provide an ecological explanation for women's BCS and CCS service utilization. Both proximal and distal factors should be considered to achieve a high coverage rate.

ADAM10 promotes the proliferation of ligamentum flavum cells by activating the PI3K/AKT pathway.

Ligamentum flavum hypertrophy (LFH) is an important cause of spinal canal stenosis and posterior longitudinal ligament ossification. Although a number of studies have focused on the mechanisms responsible for LFH, the cellular mechanisms remain poorly understood. The aim of the present study was to investigate the roles of differentially expressed genes (DEGs) in LFH, elucidate the mechanisms responsible for LFH and provide a potential therapeutic target for further studies. The GSE113212 dataset was downloaded from the Gene Expression Omnibus (GEO) database. The microarray data were analyzed and DEGs were obtained. Bioinformatics methods, such as Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and protein­protein interaction (PPI) network analyses were used to obtain the key genes and signaling pathways. In addition, cells derived from hypertrophied ligamentum flavum were cultured, and the key genes and signaling pathways in ligamentum cells were identified through in vitro cell biology and molecular biology experiments. A total of 2,123 genes were screened as DEGs. Among these DEGs, 1,384 genes were upregulated and 739 genes were downregulated. The KEGG pathway analysis revealed that the DEGs were mainly enriched in the PI3K/AKT signaling pathway, and the PPI network analysis screened A disintegrin and metalloproteinase 10 (ADAM10) as a key gene. In vitro experimental verification revealed that ADAM10 promoted the proliferation of ligamentum flavum cells and led to the hypertrophy of the ligamentum by activating the PI3K/AKT pathway. On the whole, the in vitro experimental results suggested that ADAM10 promoted the proliferation of ligamentum flavum cells by activating the PI3K/AKT pathway, which may represent a pathogenic mechanism of LFH. The findings of the present study may provide a basis and direction for further studies on the cellular mechanisms of LFH and present a potential novel therapeutic target and clinical approach.

Melatonin promotes Schwann cell proliferation and migration via the shh signalling pathway after peripheral nerve injury.

Peripheral nerve injury (PNI) is a common and incurable disease in the clinic, but the effects of available treatments are still not satisfactory. Therefore, it is necessary to explore new treatment methods. To explore the effect and mechanism of melatonin in peripheral nerve regeneration, we administered melatonin to mice with PNI by intraperitoneal injection. We applied microarray analysis to detect differentially expressed genes of mice with sciatic nerve injury after melatonin application. Then, we conducted gene ontology and protein-protein interactions to screen out the key genes related to peripheral nerve regeneration. Cell biology and molecular biology experiments were performed in Schwann cells in vitro to verify the key genes identified by microarray analysis. Our results showed that a total of 598 differentially expressed genes were detected after melatonin subcutaneously injecting into mice with sciatic nerve injury. Bioinformatics analysis showed that Shh may be the key gene for the promotion of peripheral nerve regeneration by melatonin. In vitro, the proliferation and migration abilities of schwann cells in the melatonin group were significantly higher than those of Schwann cells in the control group; while after treating with both melatonin and luzindole (a Shh signalling pathway inhibitor), the proliferation and migration abilities of Schwann cells decreased compared with the melatonin group. Our study suggests that melatonin might improve the proliferation and migration of Schwann cells via the Shh signalling pathway after PNI, thus promoting peripheral nerve regeneration. Our study provides a new approach and target for the clinical treatment of PNI.

Inactivation of ICAM1 inhibits metastasis and improves the prognosis of Ewing's sarcoma.

BACKGROUND: Ewing's sarcoma (ES) is a kind of malignant tumor, which often occurs in the long bone, pelvis, and other bone tissues, as well as some soft tissues. It often occurs in children and adolescents, second only to osteosarcoma and rhabdomyosarcoma. In the past 30 years, little progress has been made on the genomic mechanism of ES metastasis. METHODS: The gene expression sequence of ES metastasis samples was compared with that of primary tumor samples to obtain differentially expressed genes (DEGs). Subsequently, we annotated the gene functions and enriched pathways of DEGs. Additionally, the protein and protein interaction network were constructed to screen key genes that can lead to the metastasis in ES. Then, cell and molecular biology experiments were conducted to verify the results obtained from the bioinformatics analysis. Finally, we assessed the correlation of expression between the key genes EWSR and FLI1, and conducted a survival analysis of ICAM1. RESULTS: Our study revealed 153 DEGs. Of these, 82 (53.59%) were upregulated and the remaining 71 (46.41%) were downregulated. The bioinformatics analysis showed that ICAM1 was the key gene leading to the invasion and metastasis of ES. Through cell biology and molecular biology experiments, inactivation of ICAM1 inhibited the metastasis of ES cells. The survival and correlation analyses showed that ICAM1 was a risk factor in patients with ES, and that ICAM1 expression was correlated with EWSR and FLI1 expression. CONCLUSION: Our study shows that inactivation of ICAM1 inhibits metastasis and improves the prognosis of ES. Additionally, our findings provide a better understanding of the underlying mechanisms of metastatic ES, a basis for an accurate diagnosis, and therapeutic targets for ES patients.

Exendin-4 Promotes Schwann Cell Proliferation and Migration via Activating the Jak-STAT Pathway after Peripheral Nerve Injury.

Peripheral nerve injury (PNI) is a common clinical disease that causes the partial loss of segmental exercise and sensory and autonomic nervous function, placing a heavy burden on patients and their families. A previous study confirmed that exendin-4 can effectively improve nerve regeneration and functional recovery after PNI. However, the specific mechanisms by which exendin-4-mediates this repair have not been clarified. To explore the mechanism of exendin-4 in the treatment of PNI, we used microarray analysis to detect gene expression in the distal segment of the sciatic nerve after sciatic injury. Bioinformatics analyses were used to predict the roles of differentially expressed genes (DEGs) in nerve damage repair. Schwann cells (SCs) were cultured, and we verified the molecular mechanism of exendin-4 in SCs and the effect of exendin-4 on peripheral nerve regeneration through in vitro molecular biology and cell biology experiments. In vivo, exendin-4 could significantly promote peripheral nerve regeneration. A total of 180 DEGs between the exendin-4 group and the control group were detected. Bioinformatics analysis indicated that these DEGs were mainly enriched in the Jak-STAT signaling pathway. In vitro, exendin-4 could significantly promote the proliferation and migration of SCs by activating the Jak-STAT pathway, which promoted peripheral nerve regeneration. Our results indicate that exendin-4 promotes SC proliferation, migration and nerve regeneration after PNI by activating the Jak-STAT pathway. Our findings provide a basis and direction for further elucidation of the mechanisms of exendin-4 in the repair of PNI and provide a new way to treat PNI.

SCFFBXO22 targets HDM2 for degradation and modulates breast cancer cell invasion and metastasis.

Human homolog of mouse double minute 2 (HDM2) is an oncogene frequently overexpressed in cancers with poor prognosis, but mechanisms of controlling its abundance remain elusive. In an unbiased biochemical search, we discovered Skp1-Cullin 1-FBXO22-ROC1 (SCFFBXO22) as the most dominating HDM2 E3 ubiquitin ligase from human proteome. The results of protein decay rate analysis, ubiquitination, siRNA-mediated silencing, and coimmunoprecipitation experiments support a hypothesis that FBXO22 targets cellular HDM2 for ubiquitin-dependent degradation. In human breast cancer cells, FBXO22 knockdown (KD) increased cell invasiveness, which was driven by elevated levels of HDM2. Moreover, mouse 4T1 breast tumor model studies revealed that FBXO22 KD led to a significant increase of breast tumor cell metastasis to the lung. Finally, low FBXO22 expression is correlated with worse survival and high HDM2 expression in human breast cancer. Altogether, these findings suggest that SCFFBXO22 targets HDM2 for degradation and possesses inhibitory effects against breast cancer tumor cell invasion and metastasis.

PinX1 inhibits the invasion and metastasis of human breast cancer via suppressing NF-κB/MMP-9 signaling pathway.

BACKGROUND: PinX1 (PIN2/TRF1-interacting telomerase inhibitor 1) was suggested to be correlated with tumor progression. This study was designed to evaluate the role of PinX1 in human breast cancer. METHODS: To evaluate the function of PinX1 in breast cancer, we used a tissue microarray (TMA) of 405 human breast cancer patients and immunohistochemistry to analyze the correlation between PinX1 expression and clinicopathologic variables and patient survival. We also detected the abilities of cell migration and invasion in breast cancer by performing cell migration and invasion assay, gelatin zymography and western blot analysis. Lastly, we set up the nude mice model by Tail vein assay to exam the functional role of PinX1 in breast cancer metastasis. RESULTS: We found that low PinX1 expression was associated with lymph node metastasis (P = 0.002) and histology grade (P = 0.001) in patients, as well as with poorer overall and disease-specific survival (P = 0.010 and P = 0.003, respectively). Moreover, we identified that PinX1 inhibited the migration and invasion of breast cancer by suppressing MMP-9 expression and activity via NF-κB-dependent transcription in vitro. Finally, our mice model confirmed that PinX1 suppressed breast cancer metastasis in vivo. CONCLUSIONS: Our data revealed that low PinX1 expression was an independent negative prognostic factor for breast cancer patients. These findings suggested that PinX1 might be function as a tumor metastasis suppressor in the development and progression of breast cancer by regulating the NF-κB/MMP-9 signaling pathway, and might be a prognostic marker as well as a therapeutic target for breast cancer.