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BACKGROUND: Breast Cancer (BC) is a female malignancy with a high mortality rate. Novel diagnostic and prognostic biomarkers are valuable for reducing BC mortality. Our study is designed to undrape the precise role of the LINC00466/miR-4731-5p/EPHA2 axis in BC.
Methods: The Cancer Genome Atlas (TCGA) sequencing dataset was utilized to compare the levels of LINC00466. The levels of LINC00466, miR-4731-5p, and EPHA2 were tested by qRTPCR. Cell proliferation and cycle were detected by CCK-8 assay and flow cytometer. In vivo role of LINC00466 was tested by Xenograft nude models. Binding sites were predicted by TargetScan and Starbase. The binding relationship was employed by Dual-luciferase reporter gene assay and RNA pull-down assay.
Results: LINC00466 was increased in human breast cancer tissues. LINC00466 was negatively associated with miR-4731-5p and positively correlated with EPHA2 in human breast cancer tissues. Down-regulation of LINC00466 suppressed the proliferation and arrested the cell cycle of breast cancer cells, and inhibited tumor growth in vivo.
Conclusion: LINC00466 promoted BC development via mediating the miR-4731-5p/EPHA2 axis, which has the potential value as a promising therapeutic target in BC.
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DNA topoisomerase II alpha (TOP2A) expression, gene alterations, and enzyme activity have been studied in various malignant tumors. Abnormal elevation of TOP2A expression is considered to be related to the development of non-small cell lung cancer (NSCLC). However, its association with tumor metastasis and its mode of action remains unclear. Bioinformatics, real-time quantitative PCR, immunohistochemistry and immunoblotting were used to detect TOP2A expression in NSCLC tissues and cells. Cell migration and invasion assays as well as cytoskeletal staining were performed to analyze the effects of TOP2A on the motility, migration and invasion ability of NSCLC cells. Cell cycle and apoptosis assays were used to verify the effects of TOP2A on apoptosis as well as cycle distribution in NSCLC. TOP2A expression was considerably upregulated in NSCLC and significantly correlated with tumor metastasis and the occurrence of epithelial-mesenchymal transition (EMT) in NSCLC. Additionally, by interacting with the classical ligand Wnt3a, TOP2A may trigger the canonical Wnt signaling pathway in NSCLC. These observations suggest that TOP2A promotes EMT in NSCLC by activating the Wnt/ß-catenin signaling pathway and positively regulates malignant events in NSCLC, in addition to its significant association with tumor metastasis. TOP2A promotes the metastasis of NSCLC by stimulating the canonical Wnt signaling pathway and inducing EMT. This study further elucidates the mechanism of action of TOP2A, suggesting that it might be a potential therapeutic target for anti-metastatic therapy.
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Carcinoma de Pulmón de Células no Pequeñas , Movimiento Celular , ADN-Topoisomerasas de Tipo II , Transición Epitelial-Mesenquimal , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares , Proteínas de Unión a Poli-ADP-Ribosa , ADN-Topoisomerasas de Tipo II/metabolismo , ADN-Topoisomerasas de Tipo II/genética , Humanos , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Transición Epitelial-Mesenquimal/genética , Proteínas de Unión a Poli-ADP-Ribosa/metabolismo , Proteínas de Unión a Poli-ADP-Ribosa/genética , Movimiento Celular/genética , Línea Celular Tumoral , Metástasis de la Neoplasia , Vía de Señalización Wnt , Apoptosis , Masculino , Femenino , Persona de Mediana Edad , Proteína Wnt3A/metabolismo , Proteína Wnt3A/genéticaRESUMEN
BACKGROUND: PD-L1 overexpression is commonly observed in various malignancies and is strongly correlated with poor prognoses for cancer patients. Moreover, PD-L1 has been shown to play a significant role in promoting angiogenesis and epithelial-mesenchymal transition (EMT) processes across different cancer types. METHODS: The relationship between PD-L1 and vasculogenic mimicry as well as epithelial-mesenchymal transition (EMT) was explored by bioinformatics approach and immunohistochemistry. The functions of PD-L1 in regulating the expression of ZEB1 and the EMT process were assessed by Western blotting and q-PCR assays. The impact of PD-L1 on the migratory and proliferative capabilities of A549 and H1299 cells was evaluated through wound healing, cell invasion, and CCK8 assays following siRNA-mediated PD-L1 knockdown. Tube formation assay was utilized to evaluate the presence of VM structures. RESULTS: In this study, increased PD-L1 expression was observed in A549 and H1299 cells compared to normal lung epithelial cells. Immunohistochemical analysis revealed a higher prevalence of VM structures in the PD-L1-positive group compared to the PD-L1-negative group. Additionally, high PD-L1 expression was also found to be significantly associated with advanced TNM stage and increased metastasis. Following PD-L1 knockdown, NSCLC cells exhibited a notable reduction in their ability to form tube-like structures. Moreover, the levels of key EMT and VM-related markers, including N-cadherin, MMP9, VE-cadherin, and VEGFA, were significantly decreased, while E-cadherin expression was upregulated. In addition, the migration and proliferation capacities of both cell lines were significantly inhibited after PD-L1 or ZEB1 knockdown. CONCLUSIONS: Knockdown PD-L1 can inhibit ZEB1-mediated EMT, thereby hindering the formation of VM in NSCLC.
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Antígeno B7-H1 , Carcinoma de Pulmón de Células no Pequeñas , Movimiento Celular , Proliferación Celular , Transición Epitelial-Mesenquimal , Técnicas de Silenciamiento del Gen , Neoplasias Pulmonares , Neovascularización Patológica , Homeobox 1 de Unión a la E-Box con Dedos de Zinc , Humanos , Transición Epitelial-Mesenquimal/genética , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/genética , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Antígeno B7-H1/metabolismo , Antígeno B7-H1/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Neovascularización Patológica/genética , Neovascularización Patológica/metabolismo , Neovascularización Patológica/patología , Línea Celular Tumoral , Proliferación Celular/genética , Movimiento Celular/genética , Regulación Neoplásica de la Expresión Génica , Masculino , Femenino , Células A549 , Persona de Mediana EdadRESUMEN
Non-small cell lung cancer (NSCLC) is a kind of highly malignant tumor. Studies have shown that Vasculogenic mimicry (VM) may be responsible for dismal prognosis in NSCLC. Immunotherapy with programmed death-1 (PD-1) or programmed death ligand-1 (PD-L1) has significantly altered the treatment of assorted cancers, including NSCLC, but its role and mechanism in the formation of Vasculogenic mimicry (VM) in NSCLC remains unclear. This study aimed to investigate the role of the anti-PD-L1 antibody in the formation of VM in NSCLC and its possible mechanisms. The results showed that anti-PD-L1 antibody therapy could inhibit the growth of NSCLC-transplanted tumors and reduce the formation of VMs. In addition, this study found that anti-PD-L1 antibodies could increase the expression of the epithelial-mesenchymal transition (EMT) related factor E-cadherin. zinc finger E-box binding homeobox 1 (ZEB1) is an important transcription factor regulating EMT. Knocking down ZEB1 could significantly inhibit tumor growth, as well as the expression of VE-cadherin and mmp2, while remarkably increase the expression of E-cadherin. During this process, the formation of VM was inhibited by knowing down ZEB1 in both in vitro and in vivo experiments of the constructed ZEB1 knockdown stable transfected cell strains. Therefore, in this study, we found that anti-PD-L1 antibodies may reduce the formation of VMs by inhibiting the EMT process.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Antígeno B7-H1/genética , Cadherinas/genética , Cadherinas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Transición Epitelial-Mesenquimal/fisiología , Neoplasias Pulmonares/genéticaRESUMEN
BACKGROUNDS: It was highlighted by recent studies on the biological significance of vasculogenic mimicry (VM) in tumorigenicity and progression. However, it is unclear whether VM also plays a potential role in immune regulation and tumor microenvironment (TME) formation. METHODS: To identify patterns of VM alterations and VM-associated genetic features in non-small cell lung adenocarcinoma, we have screened 309 VM regulators and performed consensus molecular typing by the NMF algorithm. The ssGSEA and CIBORSORT algorithms were employed to measure the relative infiltration of distinct immune cell subpopulations. Individual tumors with immune responses were evaluated for alteration patterns of VM with typing-based differential genes. RESULTS: In 490 LUAD samples, two distinctive VM alteration patterns connected to different clinical outcomes and biochemical pathways were established. TME characterization showed that the observed VM patterns were primarily saturated with cell proliferation and metabolic pathways and higher in immune cell infiltration of the C1 type. Vasculogenic mimicry-related genes (VMRG) risk scores were constructed to divide patients with lung adenocarcinoma into subgroups with high and low scores. Patients with lower scores had better immunological scores and longer survival times. Upon further investigation, higher scores were positively correlated with higher tumor mutation burden (TMB), M1-type macrophages and immune checkpoint molecules. Nevertheless, in two other immunotherapy cohorts, individuals with lower scores had enhanced immune responses and long-lasting therapeutic benefits. Finally, we monitored the ANLN gene from the VMRG model, which was highly expressed in lung adenocarcinoma tissues and negatively correlated with prognosis; it was also highly expressed in lung adenocarcinoma cell lines, and knockdown of ANLN elicited low expression of VEGFA, MMP2 and MMP9. CONCLUSION: This study highlights that VM modifications are significantly associated with the diversity and complexity of TME, revealing new features of the immune microenvironment in lung adenocarcinoma and providing a new strategy for immunotherapy. Screening ANLN as a critical target for vasculogenic mimicry in lung adenocarcinoma provides a novel perspective for the targeted treatment of lung adenocarcinoma.
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Adenocarcinoma del Pulmón , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/terapia , Pronóstico , Inmunoterapia , Adenocarcinoma/genética , Adenocarcinoma/terapia , Puntuación de Riesgo Genético , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Microambiente Tumoral/genéticaRESUMEN
BACKGROUND: Long non-coding RNAs (lncRNAs) are critical regulators in the initiation and progression of breast cancer. Our study aims to characterize the functions of LINC02086 which few published in breast cancer and decipher the downstream molecular mechanisms. METHODS: LINC02086 expression is tested in RNA-seq data from GEPIA database, tumor tissue samples from hospital patients and breast cancer cell lines. LINC02086 was silenced or overexpressed by lenti-virus-mediated shRNAs, or pLVX-Puro plasmids. Luciferase reporter assay and RNA pull-down assay were applied to study interactions between LINC02086, miR-6757-5p and ephrin type-A receptor 2 (EPHA2). LINC02086-silencing MCF-7 cells were injected into mice to establish xenograft animal models. RESULTS: Using RNA-seq data, tumor tissue samples and breast cancer cells, LINC02086 was consistently found to be up-regulated in breast cancer, and correlated with poorer prognosis. LINC02086 knockdown decreased cell viability, promoted cell apoptosis and suppressed tumor growth. LINC02086 interacted with miR-6757-5p that interacted with EPHA2.LINC02086 expression was negatively correlated with miR-6757-5p expression (r = -0.5698, P < 0.001) but was positively correlated with EPHA2 expression (r = 0.5061, P < 0.001). miR-6757-5p expression was negatively correlated with EPHA2 expression (r = -0.5919, P < 0.001). LINC02086 regulated EPHA2 via miR-6757-5p. miR-6757-5p/EPHA2 axis was a mediator of the effect of LINC02086 on cell viability and apoptosis. CONCLUSION: LINC02086 increases cell viability and decreases apoptotic cells in breast cancer by sponging miR-6757-5p to upregulate EPHA2. This study presents LINC02086/miR-6757-5p/EPHA2 axis as promising therapeutic targets for breast cancer intervention.
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Neoplasias de la Mama , MicroARNs , ARN Largo no Codificante , Animales , Femenino , Humanos , Ratones , Apoptosis/genética , Neoplasias de la Mama/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Supervivencia Celular , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , MicroARNs/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismoRESUMEN
Type IIA topoisomerase (TOP2A) is significantly associated with malignant tumor development, invasion, treatment and its prognosis, and has been shown to be a therapeutic target against cancer. In contrast, the role of TOP2A in the immunotherapy of non-small cell lung cancer as well as in Vasculogenic mimicry (VM) formation and its potential mechanisms are unclear. The aim of this study was to investigate the role of TOP2A in proliferation, skeleton regulation, motility and VM production in non-small cell lung cancer and its mechanisms by using bioinformatics tools and molecular biology experiments. Subgroup analysis showed that the low-risk group had a better prognosis, while the high-risk group was positively correlated with high tumor mutational load, M1-type macrophage infiltration, immune checkpoint molecule expression, and immunotherapy efficacy. As confirmed by further clinical specimens, the presence of TOP2A and VM was significantly and positively correlated with poor prognosis. Our study established a model based on significant co-expression of TOP2A genes, which significantly correlated with mutational load and immunotherapy outcomes in patients with non-small cell lung cancer. Further mechanistic exploration suggests that TOP2A plays an important role in immunotherapy and VM formation in NSCLC through upregulation of Wnt3a and PD-L1 expression.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/terapia , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/metabolismo , Neovascularización Patológica/genética , Neovascularización Patológica/terapia , Neovascularización Patológica/metabolismo , Pronóstico , InmunoterapiaRESUMEN
BACKGROUND: Vasculogenic mimicry (VM) is a recently identified pattern of blood supply to tumor tissue. It has long been considered a functional element in the metastasis and prognosis of malignant tumors. Both Rho GTPase-activating protein 25 (ARHGAP25) and Ras homolog family member A (RhoA) are effective predictors of tumor metastasis. In this study, we examined the expression levels of ARHGAP25 and RhoA and the structure of VM in non-small cell lung cancer (NSCLC). At the same time, we used cytology-related experiments to explore the effect of ARHGAP25 on the migration ability of tumor cells. Furthermore, we analyzed the interaction between the three factors and their association with clinicopathological characteristics and the five-year survival time in patients using statistical tools. METHODS: A total of 130 well-preserved NSCLC and associated paracancerous tumor-free tissues were obtained. Cell colony formation, wound healing, and cytoskeleton staining assays were used to analyze the effect of ARHGAP25 on the proliferation and migration ability of NSCLC cells. Immunohistochemical staining was used to determine the positivity rates of ARHGAP25, RhoA, and VM. Statistical software was used to examine the relationships between the three factors and clinical case characteristics, overall survival, and disease-free survival. RESULTS: Cell colony formation, wound healing, and cytoskeleton staining assays confirmed that ARHGAP25 expression affects the proliferation and migratory abilities of NSCLC cells. ARHGAP25 positivity rates in NSCLC and paracancerous tumor-free tissues were 48.5% and 63.1%, respectively, whereas RhoA positivity rates were 62.3% and 18.5%, respectively. ARHGAP25 had a negative relationship with RhoA and VM, whereas RhoA and VM had a positive relationship (P < 0.05). ARHGAP25, RhoA, and VM affected the prognosis of patients with NSCLC (P < 0.05) according to Kaplan-Meier of survival time and Cox regression analyses. Furthermore, lowering ARHGAP25 expression increased NSCLC cell proliferation and migration. CONCLUSIONS: ARHGAP25 and RhoA expression is associated with VM and may be of potential value in predicting tumor metastasis, prognosis, and targeted therapy.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Proteínas Activadoras de GTPasa/metabolismo , Humanos , Neoplasias Pulmonares/patología , Neovascularización Patológica , Pronóstico , Proteína de Unión al GTP rhoA/metabolismoRESUMEN
Esophageal squamous cell carcinoma (ESCC) is one of the most common and deadly cancers. Fbxo45, a substrate recognition subunit of E3 ligase, is critically involved in tumorigenesis and tumor progression. However, the function of Fbxo45 and the underlying mechanisms have not been elucidated in ESCC. We used cellular and molecular methods to explore the molecular basis of Fbxo45-mediated ESCC development. We found that ectopic overexpression of Fbxo45 promoted the growth of Kyse-150, Kyse30 and ECA-109 cells and inhibited the apoptosis. Moreover, overexpression of Fbxo45 promoted the migration and invasion of ESCC cells. Consistently, knockdown of Fbxo45 exhibited the opposite effects on ESCC cells. Mechanistically, we observed that Fbxo45 binds to GGNBP2 via its SPRY domain and targets GGNBP2 for ubiquitination and degradation. GGNBP2 overexpression exhibited anticancer activity in ESCC cells. Furthermore, Fbxo45 exerted its functions by regulating GGNBP2 stability in ESCC cells. Notably, overexpression of Fbxo45 facilitated tumor growth in mice. Strikingly, Fbxo45 was highly expressed in ESCC tissues, and GGNBP2 had a lower expression in ESCC specimens. High expression of Fbxo45 and low expression of GGNBP2 were associated with poor prognosis in ESCC patients. Fbxo45 was negatively correlated with GGNBP2 expression in ESCC tissues. Therefore, Fbxo45 serves as an oncoprotein to promote ESCC tumorigenesis by targeting the stability of the tumor suppressor GGNBP2 in ESCC.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Proteínas F-Box , Ratones , Animales , Carcinoma de Células Escamosas de Esófago/patología , Neoplasias Esofágicas/patología , Línea Celular Tumoral , Ratones Desnudos , Ubiquitinación , Carcinogénesis , Ubiquitina-Proteína Ligasas/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas F-Box/genética , Proteínas F-Box/metabolismoRESUMEN
BACKGROUND: Tumor infiltration and metastasis are the leading causes of death for patients with tumors. Angiogenesis is a prerequisite for tumor growth and metastasis. Angiogenic factor with G patch and FHA domains 1 (AGGF1) is an angiogenic factor, whereas ubiquitin-conjugating enzyme E2C (UBE2C) functions in protein ubiquitination. Microvessel density (MVD) is the most common indicator of tumor microvessels, and vasculogenic mimicry (VM) facilitates blood supply to tumors. This study explored UBE2C and AGGF1 expression in non-small cell lung cancer (NSCLC) and their relationship with angiogenesis and prognosis to identify biological factors that might predict NSCLC infiltration, metastasis, and prognosis. METHODS: The specimens and clinical pathological data of patients with NSCLC confirmed by pathology after surgical resection between January 2013 and December 2015 were collected. UBE2C and AGGF1 expression, as well as microvessel formation and VM in NSCLC, was observed using immunohistochemistry. The relationships between UBE2C, AGGF1, MVD, VM, and clinical pathological parameters and their relationships with overall survival (OS) and disease-free survival (DFS) were analyzed. RESULTS: UBE2C and AGGF1 levels in NSCLC tissues were significantly higher than those in corresponding normal tissues (57.1% vs 15.6 and 59.7% vs 25.3%, respectively; P < 0.05). UBE2C, AGGF1, MVD, and VM were positively correlated with each other (P < 0.05) and were all related to tumor size, lymph node metastasis, and tumor-node-metastasis stage (P < 0.05). Kaplan-Meier analysis showed that patient OS and DFS in the UBE2C, AGGF1, VM-positive, and high-MVD groups were reduced (all P < 0.001). Univariate and multivariate analyses showed that UBE2C, AGGF1, VM, and MVD were independent risk factors for NSCLC prognosis. CONCLUSION: UBE2C and AGGF1 overexpression is associated with angiogenesis and poor prognosis and may be important for predicting NSCLC invasion, metastasis, and prognosis.
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Metaplastic breast carcinoma is a rare invasive breast cancer. Metaplastic breast carcinoma is mainly characterized by an epithelial or mesenchymal cell population mixed with adenocarcinoma. We collected 26 cases of metaplastic breast carcinoma in the First Affiliated Hospital of Bengbu Medical College from 2008 to 2014. Tumor size, tumor grade, vascular invasion, ER/PR status, histologic classification, and HER2/neu status were assessed for all cases and the literature was reviewed. Clinicopathologic characteristics of patients diagnosed with metaplastic breast carcinomas and its key points of differential diagnosis were discussed. All patients were female, with the median age of 50 years. The mean tumor size was 3.2 cm. 4 subtypes of metaplastic breast carcinomas were documented. Fibromatosis-like metaplastic carcinomas are typically characterized by wavy, intertwined, gentle spindle cells. When the tumor components are almost squamous cell carcinoma components and the primary squamous cell carcinoma of other organs and tissues are excluded, we can diagnose breast squamous cell carcinoma. In spindle cell carcinoma, atypical spindle cells are arranged in many ways and are usually accompanied by inflammatory cell infiltrate. Cancer with interstitial differentiation has mixed malignant epithelial and mesenchymal differentiation, and the mesenchymal components are diverse. Most tumors are triple negative. At present, surgical resection combined with chemotherapy or radiation therapy is the most effective and acceptable method for treating metaplastic breast carcinoma.
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BACKGROUND: Paired related homeobox 1 (PRRX1) and zinc finger E-box binding homeobox 1 (ZEB1) have been observed to play a vital role in the epithelial-mesenchymal transition (EMT) process in different types of cancer. The microvessel density (MVD) is the most common indicator used to quantify angiogenesis. This study aimed to investigate expression of PRRX1 and ZEB1 in non-small cell lung cancer (NSCLC) and to explore associations between these factors and tumor prognosis, EMT markers and angiogenesis. METHODS: Data for a total of 111 surgically resected NSCLC cases from January 2013 to December 2014 were collected. We used an immunohistochemical method to detect expression levels of PRRX1, ZEB1, and E-cadherin, and to assess MVD (marked by CD34 staining). SPSS 26.0 was employed to evaluate the connection between these factors and clinical and histopathological features, overall survival (OS) and tumor angiogenesis. RESULTS: PRRX1 expression was obviously lower in tumor samples than in control samples. Low expression of PRRX1, which was more common in the high-MVD group than in the low-MVD group (Pâ=â.009), correlated positively with E-cadherin expression (Pâ<â.001). Additionally, we showed that ZEB1 was expressed at higher levels in tumor samples than in normal samples. High expression of ZEB1 was associated negatively with E-cadherin expression (Pâ<â.001) and positively associated with high MVD (Pâ=â.001). Based on Kaplan-Meier and multivariate survival analyses, we found that PRRX1, ZEB1, E-cadherin and the MVD had predictive value for OS in NSCLC patients. CONCLUSIONS: These findings suggest that PRRX1 and ZEB1 may serve as novel prognostic biomarkers and potential therapeutic targets.
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Carcinoma de Pulmón de Células no Pequeñas/genética , Transición Epitelial-Mesenquimal/genética , Proteínas de Homeodominio/metabolismo , Neoplasias Pulmonares/genética , Adulto , Anciano , Biomarcadores de Tumor/genética , Cadherinas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Estudios de Casos y Controles , Femenino , Expresión Génica , Humanos , Neoplasias Pulmonares/patología , Masculino , Densidad Microvascular , Persona de Mediana Edad , Homeobox 1 de Unión a la E-Box con Dedos de ZincRESUMEN
OBJECTIVE: To investigate the expressions of Formin-like 2 (FMNL2) and Cortactin (CTTN) in gallbladder adenocarcinoma (GBAC) and their associations with the clinicopathological characteristics of the patients. METHODS: The expressions of FMNL2 and CTTN were detected with immunohistochemistry (Max Vision) in 105 GBAC tissues and 40 normal gallbladder tissues. RESULTS: The positive expression rates of FMNL2 and CTTN in normal gallbladder tissues were 25% and 20%, different from the positive expression rates of 84.76% and 86.67% in GBAC tissues (P < 0.001). The positive expression rate of FMNL2 and CTTN in GBAC correlated with tumor differentiation, tumor-node-metastasis (TNM), lymph node metastasis (LNM), and distant metastasis. FMNL2 expression was positively correlated with CTTN expression. Kaplan-Meier analysis showed that the overall survival time of patients with positive expressions group of FMNL2 and CTTN was significantly shorter than that of the negative expression group. Cox multivariate analysis showed that TNM, LNM, distant metastasis, and positive expression of FMNL2 and CTTN were independent factors influencing the prognosis of patients with GBAC (P < 0.05). CONCLUSION: The positive expression of FMNL2 and CTTN in GBAC is significantly increased, which may be related to the occurrence and development of GBAC. The combined detection of FMNL2 and CTTN may provide a scientific theoretical basis for the early diagnosis of GBAC, the development of new antitumor drugs, and the search for new targets of biotherapy.
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RATIONALE: Primary testicular lymphoma (PTL) is a rare type of extranodal non-Hodgkin's lymphoma (NHL). Although data of PTL in patients with diffuse large B-cell lymphoma (DLBCL) are accumulating, there are still patients respond poorly to prognosis. PATIENT CONCERNS: All patients had disease of the DLBCL subtype and those patients had primary involvement of the testis. In our studies, eleven patients had stage I/II disease, and 3 patients had advanced disease with B symptoms. Four patients exhibited a MYC+, BCL2+, and BCL6- expression pattern, 4 patients had a MYC+, BCL6+, and BCL2- expression pattern, and 3 patients had a MYC+, BCL2+, and BCL6+ expression pattern. Additionally, 43% (7/16) of PT-DLBCL patients had a germinal center B-cell-like (GCB) phenotype, while the others had a non-GCB phonotype. DIAGNOSES: In our case, most patients presented with unilateral painless scrotal swelling and the enlargement of the testicles in the first examination. After hospitalization, all patients underwent preoperative imageological examination of the testis and epididymis and postoperative revealed that all patients were the diffuse infiltration of a large number of anomalous lymphocytes. In addition, no invasion of other sites was observed within 3 months after diagnosis. INTERVENTIONS AND OUTCOMES: Underwent orchiectomy on the affected side was performed by urologists after all patients were diagnosed with PTL. Meanwhile, some patients received at least one course of chemotherapy, or received postoperative combined RT and chemotherapy. Because of it particularity, nineteen instances of lymph node region involvement were discovered in 12 patients since the operation. LESSONS: PT-DLBCL has unique biological characteristics, and its treatment modalities are becoming increasingly standardized. In the future, systematic interventions need to be actively considered in the early stages of PTL.
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Linfoma de Células B Grandes Difuso/metabolismo , Linfoma de Células B Grandes Difuso/patología , Neoplasias Testiculares/metabolismo , Neoplasias Testiculares/patología , Testículo/patología , Adulto , Anciano , Anciano de 80 o más Años , Quimioradioterapia/métodos , Centro Germinal/patología , Humanos , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/terapia , Linfoma no Hodgkin/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Orquiectomía/métodos , Fenotipo , Pronóstico , Estudios Retrospectivos , Neoplasias Testiculares/terapia , Testículo/diagnóstico por imagen , Ultrasonografía/métodosRESUMEN
OBJECTIVE: To investigate the role of FOXM1, ß-catenin and TCF4 in esophageal cancer (EC) and their relationship to VM (Vasculogenic Mimicry). METHODS: CCK-8 were performed to examine EC cell proliferation in FOXM1 silenced cells. EC cell migration and invasion were investigated through wound healing and Transwell assays, respectively. The formation of pipe like structures were assessed in 3D cultures. The expression of Foxm1, ß-catenin, Tcf4 and E-cadherin were investigated through western blot, RT-qPCR and immunohistochemistry (IHC) staining. The relationship between FOXM1 expression, clinic-pathological features, and overall survival (OS) were further analyzed. RESULTS: A loss of FOXM1 expression correlated with the OS of ESCC patients. FOXM1 silencing led to a loss of cell growth and suppressed cell migration and invasion in ESCC cells. VM structures were identified in ESCC tissues and human EC cell lines. Mechanistically, FOXM1 was found to promote tumorigenesis through the regulation of ß-catenin, Tcf4, and E-cadherin in EC cells, leading to the formation of VM structures. CONCLUSIONS: These findings highlight FoxM1 as a novel therapeutic target in ESCC.
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Neoplasias Esofágicas/patología , Proteína Forkhead Box M1/metabolismo , Invasividad Neoplásica/patología , Factor de Transcripción 4/metabolismo , beta Catenina/metabolismo , Adulto , Anciano , Cadherinas/metabolismo , Línea Celular Tumoral , Movimiento Celular/fisiología , Proliferación Celular/fisiología , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica/genéticaRESUMEN
Alpha-B crystallin (CRYAB), as a small heat shock protein, has been found to be highly expressed in various human cancers and significantly associated with the unfavorable prognosis of these tumor. Nevertheless, the clinical significance of CRYAB in gastric cancer (GC) angiogenesis remains to be elucidated. In this study, we evaluated the expression of CRYAB and CD34 in GC tissues and corresponding normal gastric specimens to explore whether high level CRYAB is related with the angiogenesis and the poor prognosis in GC.In this study, the expression of CRYAB and CD34 were detected in GC tissues and corresponding normal gastric tissues by immunohistochemical (IHC) technique. Furthermore, the relationship of CRYAB with CD34-evaluated microvessel density (MVD) and poor prognosis was also investigated.CRYAB expression level was significantly higher in GC tissue than in normal gastric mucosa tissue, and clearly mean higher MVD was observed in tumor tissues compared with non-cancerous tissues. Besides, higher MVD value was observed in positive CRYAB expression group than in negative CRYAB expression group. Statistical analysis showed that CRYAB and MVD are associated with clinicopathological features including lymph node metastasis (LNM), tumor differentiation, invasion depth, and TNM stages. Kaplan-Meier method and multivariate survival analysis indicated that high expression of CRYAB, MVD, invasion depth, TNM stages, and tumor differentiation, as well as LNM significantly correlate with poor prognosis of GC patients.High expression of CRYAB may contribute to angiogenesis, invasion and metastasis of GC. These results indicated that CRYAB was expected to be a promising molecular marker for poor prognosis and potential therapeutic target in patients with GC.
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Antígenos CD34/metabolismo , Neoplasias Gástricas/patología , Regulación hacia Arriba , Cadena B de alfa-Cristalina/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Metástasis Linfática , Masculino , Invasividad Neoplásica , Estadificación de Neoplasias , Pronóstico , Neoplasias Gástricas/metabolismo , Análisis de SupervivenciaRESUMEN
Occurrence of lymphoma of the female genital tract (FGT) is extremely rare, and cohort studies on survival rates of affected patients are sparse. The aim of this study was to retrospectively evaluate the clinicopathological characteristics of patients diagnosed with non-Hodgkin lymphoma of the FGT. This study included 25 women diagnosed with lymphoma of the FGT. Their data on presenting pathological subtype, International Federation of Gynecology and Obstetrics (FIGO) and Ann Arbor staging, International Prognostic Index (IPI) score, treatment, and survival time were collected. Among the 25 patients, the most prevalent histological subtype was diffuse large B-cell lymphoma (23/25). Tumors were most commonly located in the ovary (15/25), with the remainder located in the cervix (7/25) and uterine corpus (3/25). 76% of cases by Ann Arbor were stage III or IV, and 70% of cases by FIGO were stage III or IV. The overall median survival from diagnosis of lymphoma was estimated to be 71 months, with 3-year and 5-year survival rates of 92% and 80%, respectively. The FIGO and Ann Arbor staging and IPI score were significantly correlated with overall survival time.
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Accumulated evidence shows that sperm-associated antigen 6 (SPAG6) gene has multiple biological functions. It maintains the normal function of a variety of cells including ciliary/flagellar biogenesis and polarization, neurogenesis, and neuronal migration. Moreover, SPAG6 is found to be critically involved in auditory transduction and the fibroblast life cycle. Furthermore, SPAG6 plays an essential role in immuno-regulation. Notably, SPAG6 has been demonstrated to participate in the occurrence and progression of a variety of human cancers. New evidence shows that SPAG6 gene regulates tumor cell proliferation, apoptosis, invasion, and metastasis. Therefore, in this review, we describe the physiological function and mechanism of SPAG6 in human normal cells and cancer cells. We also highlight that SPAG6 gene may be an effective biomarker for the diagnosis of human cancer. Taken together, targeting SPAG6 could be a novel strategy for the treatment of human diseases including cancer.
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Vasculogenic mimicry (VM) involves a tubular structure with a basement membrane that is similar to and communicates with vessels but functions independent of blood vessels to nourish tumor cells, promote tumor progression, invasion, and metastasis, with reduced 5-year survival rates. Tumor cell proliferation, invasion, and metastasis are promoted by the epithelial-mesenchymal transition (EMT). Paired-related homeobox 1 (PRRX1), a newly discovered EMT inducer, has been shown to correlate with metastasis and prognosis in diverse cancer types. Cancerous inhibitor of protein phosphatase 2A (CIP2A) was initially recognized as an oncoprotein. In this study, we aimed to investigate the expression and clinical significance of the EMT markers PRRX1, CIP2A and VM in clear cell renal cell carcinoma (CCRCC) and their respective associations with clinicopathological parameters and survival.Expression of PRRX1, CIP2A and VM in whole CCRCC tissues from 110 patients was analyzed by immunohistochemical and histochemical staining. Fisher's exact test or the chi square test was used to assess associations with positive or negative staining of these markers and clinicopathological characteristics.Positive expression of CIP2A and VM presence was significantly higher and that of PRRX1 was significantly lower in CCRCC tissues than in corresponding normal tissues. Furthermore, positive expression of CIP2A and VM was significantly associated with tumor grade, size, lymph node metastasis (LNM) stage, and tumor node metastasis (TNM) stage and inversely associated with overall survival time (OST). Moreover, levels of PRRX1 were negatively associated with tumor grade, size, LNM stage, and TNM stage. The PRRX1 subgroup had a significantly longer OST time than did the PRRX1 subgroup. In multivariate analysis, high VM and CIP2A, tumor grade, LNM stage, TNM stage, and low PRRX1 levels were identified as potential independent prognostic factors for OST in CCRCC patients.VM and expression of CIP2A and PRRX1 represent promising biomarkers for metastasis and prognosis and potential therapeutic targets in CCRCC.
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Autoantígenos/metabolismo , Carcinoma de Células Renales/metabolismo , Proteínas de Homeodominio/metabolismo , Neoplasias Renales/metabolismo , Proteínas de la Membrana/metabolismo , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Renales/diagnóstico , Carcinoma de Células Renales/patología , Femenino , Humanos , Péptidos y Proteínas de Señalización Intracelular , Riñón/patología , Neoplasias Renales/diagnóstico , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , PronósticoRESUMEN
AIMS: This study was conducted to explore the function of microRNA-141-3p/cyclin-dependent kinase 8 (miR-141-3p/CDK8) in regulating trastuzumab resistance of breast cancer cells. MATERIALS AND METHODS: Microarray analysis was performed to screen microRNAs that are differentially expressed in wild type and trastuzumab-resistant (TR) breast cancer cell lines. TargetScan helped predict the target gene of miR-141-3p. The regulatory relationship was confirmed through a luciferase reporter assay, quantitative reverse transcriptase polymerase chain reaction, and Western blot analysis. The MTT assay, transwell invasion assay, and wound scratch assay were performed to measure the proliferative, invasive, and migratory ability of breast cancer cells, respectively. Tumor cell xenografts in nude mice were conducted to observe the effect of miR-141-3p on trastuzumab resistance in breast cancer cells in vivo. The enzyme-linked immunosorbent assay was used to detect protein secretion. RESULTS: miR-141-3p was downregulated in the drug-resistant cell lines. CDK8 was proved to be a target gene of miR-141-3p. Transfection of miR-141-3p or CDK8 small interfering RNA (siRNA) reversed the resistance to trastuzumab in TR cell lines and suppressed cell invasion and migration. Dysregulation of transforming growth factor beta (TGF-ß) was detected when the expression of CDK8 was silenced by CDK8 siRNA, and downregulation of TGF-ß had a notable effect on reducing the phosphorylation of SMAD2/SMAD3. CONCLUSION: miR-141-3p could restore the sensitivity to trastuzumab in breast cancer cells by repressing CDK8, which might regulate the phosphorylation levels of SMAD2/SMAD3 via TGF-ß.