This study aimed to investigate the clinicopathological features and prognostic indicators of alveolar soft part sarcoma (ASPS).
The characteristics of 26 ASPS patients diagnosed at our hospital ...between January 2011 and January 2019 were retrospectively analysed.
The data for 12 male and 14 female patients, with a median age of 27.5 years, were assessed. The clinical symptoms mainly included painless enlarged masses in deep soft tissues. ASPS had a characteristic pathological morphology. Twenty-four patients were positive for TFE3, and TFE3 gene rearrangement was detected in 12 patients. Among the 26 patients who completed follow-up, 14 had metastasis, 1 had local recurrence, and 7 died. Kaplan-Meier survival analysis revealed that prognosis was significantly correlated with sex, tumour size and metastasis (P < 0.05). Multivariate Cox regression analysis revealed that sex and metastasis were independent prognostic risk factors for patients with ASPS (P < 0.05).
ASPS is a rare soft tissue sarcoma of unknown origin that occurs in young people, has a slow but metastatic course, and is associated with a poor 5-year survival rate among patients with metastasis. ASPS has character TFE3 protein and gene expression, and the diagnosis is relatively specific. The diagnosis requires comprehensive analysis of clinical history, histological morphology, and immunohistochemistry.
To investigate the role of FOXM1, β-catenin and TCF4 in esophageal cancer (EC) and their relationship to VM (Vasculogenic Mimicry).
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, β-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.
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 β-catenin, Tcf4, and E-cadherin in EC cells, leading to the formation of VM structures.
These findings highlight FoxM1 as a novel therapeutic target in ESCC.
Background. Chitinase-3-like protein 1 (CHI3Ll) has been identified as a novel tumor marker in several cancers. The objective of this study was to detect the expression of Chitinase-3-like protein 1 ...(CHI3L1) and CD31-labeled microvessel density (MVD) in cervical squamous cell carcinoma (CSCC) and to assess its prognostic impact. Methods. Elivision™ plus immunohistochemical method was used to detect CHI3L1 expression and MVD in different cervical tissues. We analyzed the relationship between CHI3L1 and MVD in CSCC tissues and investigated the relationship between CHI3L1, MVD, and clinicopathological parameters. Univariate and multivariate survival analyses were performed to assess the impact on progression-free survival (PFS) and overall survival (OS). Results. The positive expression rate of CHI3L1 protein in CSCC tissues (69.9%, 72/103) was significantly higher than that in high-grade cervical intraepithelial lesions (53.3%, 32/60), low-grade cervical intraepithelial lesions (25%, 15/60), and normal cervical tissues (16.7%, 10/60). MVD values ranged from 6 to 64 in CSCC, and no microvascular formation was observed in normal cervical tissues, high-grade intraepithelial lesions, or low-grade intraepithelial lesions. The high expression of CHI3L1 and MVD was significantly correlated with the invasion depth, differentiation degree, vascular invasion, and lymph node metastasis of CSCC (all P<0.05). In CSCC, the expression of MVD in the CHI3L1 high-expression group (41.35±9.056) was significantly higher than that in the CHI3L1 low-expression group (23.26±11.000, P<0.05). On univariate Kaplan–Meier analysis, FIGO stage, tumor diameter, lymph node metastasis, vascular invasion, CHI3L1, and MVD of CSCC were related to the prognosis of PFS and OS (all P<0.05); however, CHI3L1 and MVD were not independent prognostic factors. Conclusion. CHI3L1 may be involved in the progression of cervical cancer. Its high expression can promote neovascularization in the tumor microenvironment. CHI3L1 is a potential therapeutic target in the context of cervical cancer.
Esophageal squamous cell carcinoma (ESCC) is a predominant type of esophageal cancer, which is a malignant tumor originating from the esophageal mucosa or gland and is aggressive with poor prognosis. ...Identification of new gene expression patterns would be helpful for providing new targets for the early detection and treatment of ESCC patients. In the present study, we employed cDNA array technology to compare gene expression profiles between ESCC tissues and adjacent normal epithelial tissues from ESCC patients. There was at least a 4-fold change in the expression levels of 72 genes that were significantly increased and 107 genes that were decreased in ESCC compared with normal esophageal epithelium. Among them, genes known to be involved in ESCC were found, including matrix metalloproteinases, transcription factors SOX-4 and SOX-17, the Wingless-type MMTV integration site family member 2, and cell cycle regulators. Moreover, we have newly identified the two genes that are down-regulated in ESCC: monoamine oxidase A, an enzyme that catalyzes monoamines oxidation and 15-hydroxyprostaglandin dehydrogenase NAD+, a prostaglandin-synthesizing enzyme that physiologically antagonizes COX-2. Likewise, we found the three genes that are up-regulated in ESCC: CD7, a cell surface glycoprotein member of the immunoglobulin superfamily, LIM-domain kinase 1, a small subfamily with an unique combination of two N-terminal LIM motifs and a C-terminal protein kinase domain, and TTK protein kinase, a previously unidentified member of the kinase family. These newly identified genes may be involved in the progression of the tumor and/or represent properties specific to ESCC.
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.
Background. This study aimed to explore the relationships between the sex-determining region on Y (SRY) box transcription factor 17 (SOX17), Cyclin D1, vascular endothelial cadherin (VE-cadherin), ...and vasculogenic mimicry (VM) in the occurrence and development of esophageal squamous cell carcinoma (ESCC). Methods. The expressions of SOX17, Cyclin D1, and VE-cadherin, as well as VM, in tissues, were determined using immunohistochemistry. SOX17, Cyclin D1, and VE-cadherin mRNA in ESCC and their corresponding adjacent normal tissues were quantified using quantitative reverse transcription polymerase chain reaction analysis. Cell invasion, migration, and proliferation were determined after the silencing of VE-cadherin. SOX17, Cyclin D1, and VE-cadherin protein were quantified using Western blotting. Results. The expression levels of SOX17, Cyclin D1, and VE-cadherin significantly correlated with the clinical characteristics of ESCC. After the VE-cadherin silencing, cell invasion, migration, and proliferation decreased, along with the Cyclin D1 levels, while the SOX17 levels increased. Conclusion. SOX17, Cyclin D1, and VE-cadherin are involved in the development of ESCC.
sFPR1 plays an important role in colorectal carcinoma (CRC) tumorigenesis, Slug is also considered to be related to the development of CRC. However, the relationship between them and the mechanism of ...their involvement in CRC metastasis remain unknown. In this study, immunohistochemistry (IHC) was used to detect the expression of sFPR1, β-catenin, and Slug in 145 samples of CRC and corresponding surrounding "normal" mucosa tissues. Furthermore, clinicopathological features such as age, sex and so on were also collected retrospectively. Western blot and Transwell were used to detect proteins expression and migration capacity. In present study, the expression of sFPR1, Slug and β-catenin proteins were significantly correlated with lymph node metastasis and tumor-node-metastasis (TNM) stage of patients with CRC. sFPR1 expression showed a negative correlation with Slug and β-catenin. Kaplan-Meier analysis indicated that the postoperative 5-year OS of patients was related to the expression of sFPR1 and Slug, multivariate Cox regression analysis revealed that sFPR1 expression was an independent prognostic factor for CRC patients. Moreover, we found that the expression of slug and β-catenin could be regulated by sFPR1 in SW480 cells, and migration capacity of SW480 cells was suppressed with sFPR1 restoration. In summary, our data suggest that sFRP1, Slug and β-catenin are related to metastasis and prognosis in CRC. sFPR1 could mediate CRC metastasis by regulating the expression of Slug and β-catenin. Combined detection of these factors may be of significant value in predicting the metastasis and prognosis in CRC patients.
Vasculogenic mimicry (VM) plays an important role in invasion and metastasis of malignant tumor. High expression of vascular endothelial cadherin (VE-cahderin) in malignant tumor cells can promote ...the formation of VM. High expression of SOX4 (sex-determining region Y-related high-mobility group box 4) was found in esophageal squamous cell carcinoma (ESCC). It can promote the development of epithelial stromal transformation. Then, SOX4 can promote the formation of VM in ESCC.
Paraffin-embedded specimens of ESCC (with complete clinicopathological data) and normal esophageal mucosa adjacent to carcinoma (> 5 cm) were collected from January to December 2013. CD34/PAS was used to detect VM. The expression of VE-cadherin and SOX4 was used by immunohistochemistry. The patients were followed up in detail (survival time and survival status).
SOX4, VM, and VE-cadherin were highly expressed in ESCC. Moreover, they were positively correlated. Survival analysis shows that the expressions of SOX4, VM, and VE-cadherin are associated with the patient's prognosis and can be independent prognostic factors for ESCC.
Studies suggests that SOX4, which is highly expressed in ESCC, is involved in the formation of VM. The combined detection of SOX4, VE-cadherin and VM expression can be used as biomarkers for invasion and metastasis of ESCC. These three markers can be used as powerful prognostic factors in patients with ESCC.
Epithelioid hemangioendothelioma (EHE) is a rare medium-to-low-grade malignant vascular tumor characterized by vascular differentiation along with specific morphological and genetic alterations. ...Approximately 90% and 5% of EHE cases are associated with the
WWTR1-CAMTA1
and
YAP1/TFE3
fusion gene, respectively. Therefore, nuclear CAMTA1 protein expression is considered to be an effective marker for EHE diagnosis. However, the specificity and reliability of this approach have recently been put into question. The purpose of this study was to compare the detection of CAMTA1 expression in cases of EHE and histologic mimics using fluorescence
in situ
hybridization (FISH) and conventional protein immunohistochemistry via hematoxylin and eosin staining. Fifteen EHE and 37 histologic mimic samples were immunohistochemically stained with polyclonal anti-CAMTA1 antibody to evaluate the nuclear protein expression level of CAMTA1. In addition, 15 EHE samples and 10 vascular tumor samples were subjected to FISH to detect the
WWTR1-CAMTA1
fusion gene. Histologically, EHE typically showed a mucous hyaline or cartilaginous stroma, often forming a primitive vascular lumen, and expressed vascular endothelial markers. Twelve of the 15 EHE samples showed positive nuclear CAMTA1 expression with immunohistochemistry, whereas six of the 37 histologic mimics showed positive nuclear expression. FISH detected a red-green signal fusion in 14 of the 15 cases of EHE, but in none of the 10 vascular tumors. These results indicate that CAMTA1 is an effective and useful EHE marker, but that FISH fusion gene detection has better diagnostic value and clinical significance.
SOX4 is highly expressed in many different tumor types, and SOX4 has been reported in the literature to participate in tumor proliferation, damaging and movement by leading Epithelial-Mesenchymal ...Transition. Cancer vital cells and Epithelial-Mesenchymal Transition have been repeatedly confirmed to participate during the proliferation, damaging and movement of cancer. This research examined the association of the Epithelial-Mesenchymal Transition-related molecules E-cadherin, N-cadherin, CD44, and SOX4 in the ESCC and aimed for providing inspiration for clinical treatment as well as to indicate a new direction for detecting invasion and forecasting the prospect of affected role using ESCC.
Immunohistochemistry was utilized to observe the expression of the S0X4, N-cadherin, CD44 and E-cadherin proteins. Survival analysis of the positive and negative SOX4, E-cadherin, N-cadherin and CD44 protein expression groups was performed by the Kaplan-Meier approach.
A confirming relationship was observed among the expression of SOX4, N-cadherin or CD44 and tumor diameter, distant metastasis, deepness of damaging, lymph node metastasis, pTNM stage and histological grade (
<0.05). Spearman correlativity calculation displayed that the expression of the SOX4 protein was obviously responded with the expression of the N-cadherin and CD44 proteins. Moreover, the expression of the N-cadherin and CD44 proteins was also positively correlated. The E-cadherin protein was negatively correlated with SOX4, N-cadherin and CD44 protein expression in ESCC. SOX4, N-cadherin, CD44, E-cadherin, age and distant metastasis were determined to be separate elements that influenced the prognosis of patients with ESCC.
We found that suppression of ESCC providers can suppress the growth of bad tumors and change therapeutic results for ESCC patient since CD44 supports the induction of Epithelial-Mesenchymal Transition in ESCC.
PDF
