Inflammation and Prostate Cancer: A Multidisciplinary Approach to Identifying Opportunities for Treatment and Prevention.

Prostate cancer is a major cause of disease for men globally. Inflammation, an established hallmark of cancer, is frequently observed in the prostate, though its contribution to prostate cancer risks and outcomes is not fully understood. Prostate cancer is biologically and clinically heterogeneous, and there is now evidence that inflammation and immunological characteristics vary by the genomic and mutational landscape of the tumor. Moreover, it is now recognized that risk factor profiles vary between tumor subgroups, as defined by histopathological and molecular features. Here, we provide a review centered around the relationship between inflammation and prostate cancer, with a consideration of molecular tumor features and a particular focus on the advanced and lethal stages of disease. We summarize findings from epidemiological studies of the etiology and role of inflammation in prostate cancer. We discuss the pathology of prostate inflammation, and consider approaches for assessing the tumor immune microenvironment in epidemiological studies. We review emerging clinical therapies targeting immune biology within the context of prostate cancer. Finally, we consider potentially modifiable risk factors and corresponding lifestyle interventions that may affect prostate inflammation, impacting outcomes. These emerging insights will provide some hints for the development of treatment and prevention strategies for advanced and lethal prostate cancer.

Melatonin ameliorates bupivacaine-induced spinal neurotoxicity in rats by suppressing neuronal NLRP3 inflammasome activation.

Bupivacaine is a common local anesthetic that causes neurotoxicity when used at clinical concentrations. Melatonin (MT), is a potent neuroprotective molecule. The study aimed to characterize the neuroprotective effects of MT on spinal neurotoxicity induced by bupivacaine in rats. It showed that bupivacaine, by intrathecal injection, induced spinal injury, and that the protein levels of Nod-like receptor protein 3 (NLRP3), cleaved caspase-1, and the N-terminal region of gasdermin D (GSDMD-N) were significantly increased. NLRP3 was expressed mainly in neurons and microglia. MT treatment ameliorated bupivacaine-induced spinal cord injury in rats by suppressing activation of neuronal NLRP3 inflammasomes.

Bioinformatics Analysis of miRNAs Targeting TRAF5 in DLBCL Involving in NF-κB Signaling Pathway and Affecting the Apoptosis and Signal Transduction.

Background: Diffuse large B-cell lymphoma (DLBCL) is an aggressive B-cell lymphoma with high heterogeneity. There is an unmet need to investigate valid indicators for the diagnosis and therapy of DLBCL. Methods: GEO database was utilized to screen for differentially expressed genes (DEGs) and differential miRNAs in DLBCL tissues. The Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were applied to analyse DEGs. Then multiple databases were searched for related miRNAs within DLBCL, TNF receptor-associated factor 5 (TRAF5) and NF-kappa B (NF-κB) signaling pathways. The KOBAS database was used to assist in the screening of miRNAs of interest and construct the regulatory network of miRNA-mRNA. Finally, the expression level and diagnostic performance of miRNAs were analyzed with GEO datasets, and DEGs were identified from the GEPIA database. Results: DEGs were significantly concentrated in the NF-κB signaling pathway and cytokine-cytokine receptor interaction, and involved in the process of immune response and protein binding. MiR-15a-5p, miR-147a, miR-192-5p, miR-197-3p, miR-532-5p, and miR-650 were revealed to be targeting TRAF5 and participating in NF-κB signaling pathway and might impact the apoptosis and signal transduction of DLBCL. In the GEPIA database, TRAF5 was significantly overexpressed in DLBCL. The expression of miR-197-3p was upregulated within GEO datasets, while the rest of the miRNAs were downregulated in DLBCL. Conclusions: Subsets of miRNAs may participate in the NF-κB signaling pathway by co-targeting TRAF5 and could be prospective biomarkers exploring the pathogenesis of DLBCL.

Identifying the Prognostic Risk Factors of Synaptojanin 2 and Its Underlying Perturbations Pathways in Hepatocellular Carcinoma.

Synaptojanin 2 (SYNJ2) regulates cell proliferation and apoptosis via dephosphorylating plasma membrane phosphoinositides. Aim of this study is to first seek the full-scale expression levels and potential emerging roles of SYNJ2 in hepatocellular carcinoma (HCC). We systematically analyzed SYNJ2 mRNA expression and protein levels in HCC tissues based on large-scale data and in-house immunohistochemistry (IHC). The clinical significance and risk factors for SYNJ2-related HCC cases were identified. A nomogram of prognosis was created and its performance was validated by concordance index (C-index) and shown in calibration plots. Based on the identified differentially coexpressed genes (DCGs) of SYNJ2, enriched annotations and potential pathways were predicted, and the protein interacting networks were mapped. Upregulated SYNJ2 in 3,728 HCC and 3,203 non-HCC tissues were verified and in-house IHC showed higher protein levels of SYNJ2 in HCC tissues. Pathologic T stage was identified as a risk factor. Upregulated mRNA levels and mutated SYNJ2 might cause a poorer outcome. The C-index of the nomogram model constructed by SYNJ2 level, age, gender, TNM classification, grade, and stage was evaluated as 0.643 (95%CI = 0.619-0.668) with well-calibrated plots. A total of 2,533 DCGs were extracted and mainly functioned together with SYNJ2 in metabolic pathways. Possible transcriptional axis of CTCF/POLR2A-SYNJ2/INPP5B (transcription factor-target) in metabolic pathways was discovered based on ChIP-seq datasets. In summary, transcriptional regulatory axis CTCF/POLR2A-SYNJ2 might influence SYNJ2 expression levels. Increased SYNJ2 expression level could be utilized for predicting HCC prognosis and potentially accelerates the occurrence and development of HCC via metabolic perturbations pathways.

Expression and clinical significance of neuropilin-1 in Epstein-Barr virus-associated lymphomas.

BACKGROUND: The expression of neuropilin-1 (NRP-1) in Epstein-Barr virus (EBV)-associated lymphomas and its relationships with clinicopathological parameters was investigated. METHODS: The researchers compared 111 cases of patients with lymphoma to 20 cases of reactive lymphoid hyperplasia. In situ hybridization was applied to observe the expression of EBV-encoded RNA (EBER) in lymphomas, and immunohistochemistry was used to detect the NRP-1 expression in lymphoma tissues and lymph node tissues with reactive hyperplasia. RESULTS: In these 111 cases, the EBER of 62 cases (55.9%) appeared positive. NRP-1 was relatively highly expressed in lymphomas (P= 0.019). Further, NRP-1 showed higher expression in lymphomas with positive EBER than in negative ones. A comprehensive analysis revealed that NRP-1 was differently expressed in NK/T-cell lymphoma, Hodgkin's lymphoma, diffuse large B-cell lymphoma, and anaplastic large cell lymphoma (P= 0.027). Moreover, highly expressed NRP-1 was found to be a useful independent prognostic factor in assessing overall survival and progression-free survival rates in cases of non-Hodgkin's lymphoma (NHL). CONCLUSIONS: NRP-1 exhibited higher expression in lymphomas, and it was positively expressed in EBV-positive lymphomas. Moreover, highly expressed NRP-1 can be used as an undesirable independent prognostic factor in NHL.

Erratum: Expression of exportin-1 in diffuse large B-cell lymphoma: immunohistochemistry and TCGA analyses.

[This corrects the article on p. 5547 in vol. 11, PMID: 31949642.].

Expression and clinical significance of ubiquitin­specific­processing protease 34 in diffuse large B­cell lymphoma.

Ubiquitin­specific­processing protease 34 (USP34) is a deubiquitinase that is involved in the pathogenesis of various cancers. Its roles in diffuse large B­cell lymphoma (DLBCL) are unknown. The present study aimed to determine the level of USP34 expression and to explore its association with clinicopathological features and prognosis in patients with DLBCL; a total of 30 cases of reactive lymphoid hyperplasia and 131 cases of DLBCL were included in this study. The level of USP34 expression was examined by immunohistochemistry (IHC), and correlations between USP34 expression and clinicopathological features and prognosis were analyzed. In addition, mutations, expression and clinical significance of USP34 in DLBCL were evaluated using data from The Cancer Genome Atlas (TCGA). USP34 expression was significantly higher in DLBCL compared with expression in reactive lymphoid hyperplasia. In DLBCL, overexpression of USP34 was associated with older age, germinal center B cell­like (GCB) subtype, multiple extranodal involvements and higher International Prognostic Index (IPI) scores. No significant association was identified between USP34 protein level and patient survival. In the TCGA dataset, low USP34 mRNA expression was demonstrated to be associated with a poor disease­free survival (DFS), but not with overall survival (OS) in patients with DLBCL. In conclusion, high expression of USP34 protein in DLBCL was associated with older age, GCB subtype, multiple extranodal involvement and high IPI scores of DLBCL. USP34 may be a valuable marker for the assessment of patients with DLBCL, and further studies are needed to clarify USP34 expression on DLBCLs.

The expression of CCL18 in diffuse large B cell lymphoma and its mechanism research.

BACKGROUND: Molecular target therapy has become a hot spot in cancer treatment, finding effective targets for diffuse large B cell lymphoma (DLBCL) is an urgent problem. OBJECTIVE: To detect the expression level of C-C motif chemokine ligand 18 (CCL18) in DLBCL and clarify its potential role in the progression of DLBCL. METHODS: Gene expression datas of DLBCL were obtained from TCGA and GEO databases. The relationship between CCL18 and clinicopathologic information of DLBCL was assessed using meta-analysis method. Then we conducted bioinformatics analysis to uncover the biological function of CCL18 and its co-expression genes. Immunohistochemistry was applied to detect expression of CCL18 in DLBCL and reactive hyperplasia lymphoid tissues. RESULTS: The expression of CCL18 in DLBCL was higher than negative control group. The levels of CCL18 were distinct in different molecular subtypes and ages, and patients with higher level of CCL18 had a shorter overall survival than those with lower level. CCL18 and its co-expression genes were enriched in biological function such as cell proliferation, migration, apoptotic, and correlated with NF-κB, pathway in cancer, PI3K-AKT pathway. CONCLUSIONS: CCL18 was up-regulated in DLBCL and related to poor prognosis. CCL18 may act as a valuable target for diagnosis and treatment of DLBCL.

LncRNA UCHL1-AS1 prevents cell mobility of hepatocellular carcinoma: a study based on in vitro and bioinformatics.

We set out to investigate biological functions and potential molecular mechanisms of long non-coding RNA (lncRNA) in hepatocellular carcinoma (HCC). HCC cell line Bel-7404 was cultured and transfected with antisense to the ubiquitin carboxyl-terminal hydrolase L1 (UCHL1-AS1). Viability and mobility were detected by MTT and wound healing assays. Additionally, enrichment analysis and functional networks of UCHL1-AS1 related genes in HCC were performed. Results showed that high level UCHL1-AS1 could effectively inhibit HCC cell migration. However, there was no significant correlation between overexpressed UCHL1-AS1 and HCC proliferation. Meanwhile, BMP4, CALM3, and HRAS were selected from 204 genes that related to UCHL1-AS1. All of these hub genes play critical roles in HCC occurrence and development. Thus, underlying molecular mechanisms among hub genes and UCHL1-AS1 in HCC might be valuable for prognosis and treatment.

Expression of exportin-1 in diffuse large B-cell lymphoma: immunohistochemistry and TCGA analyses.

Exportin-1 (XPO1) is an essential nuclear export receptor that is involved in the pathogenesis of multiple tumors. However, the role of XPO1 in diffuse large B-cell lymphoma (DLBCL) requires clarification. This study aims to detect XPO1 expression in DLBCL and to explore its relationships with clinicopathologic parameters and prognoses. METHODS: A total of 131 cases of DLBCL and 30 cases of reactive lymphoid hyperplasia were selected for immunohistochemistry to examine XPO1 expression and analyze the relationships of XPO1 expression with clinicopathologic parameters and prognosis. DLBCL datasets downloaded from The Cancer Genome Atlas (TCGA) were used to analyze the mutations, expressions, and clinical values of XPO1 in DLBCL. RESULTS: XPO1 expression was markedly upregulated in DLBCL compared to the reactive lymphoid hyperplasia group (χ2 = 10.734, P = 0.001). High XPO1 expression was associated with an advanced clinical stage (χ2 = 4.036, P = 0.045) and a risky International Prognostic Index (IPI) score (χ2 = 5.301, P = 0.025). Moreover, high XPO1 expression was associated with a lower overall survival rate compared with low expression (P = 0.043). XPO1 was an independent prognostic factor for DLBCL (risk ratio, RR = 3.772, P = 0.006). Furthermore, XPO1 overexpression in DLBCL was correlated with a high IPI score (P = 0.024) in TCGA datasets. CONCLUSION: High XPO1 expression in DLBCL was related to an advanced clinical stage, poor IPI score, and poor prognosis. Thus, XPO1 may be useful for condition identification and prognostic assessment.

Potential role of microRNA­223­3p in the tumorigenesis of hepatocellular carcinoma: A comprehensive study based on data mining and bioinformatics.

The aims of the present study were to examine the potential role of microRNA­233­3p (miR)­223­3p in the tumorigenesis of hepatocellular carcinoma (HCC), and to investigate its diagnostic accuracy and potential molecular mechanisms. The expression data of miR­223­3p in HCC were obtained from the Gene Expression Omnibus (GEO). Data for the precursor miR­223 were obtained from The Cancer Genome Atlas (TCGA). The diagnostic role of miR­223­3p was identified by the receiver operating curve (ROC), and the diagnostic value of miR­223­3p in HCC was calculated from qualified reports in the literature. In addition, associated data from the GEO, TCGA and qualified experiments were pooled for comprehensive meta­analysis. Genes, which intersected between online prediction databases, natural language processing and differentially expressed genes from TCGA were regarded as potential targets of miR­223­3p in HCC. The Gene Ontology enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes pathways of potential targets were performed using the Database for Annotation, Visualization and Integrated Discovery. The protein­protein interactions were mapped using the Search Tool for the Retrieval of Interacting Genes. Among 15 qualified microarray data sets from GEO, seven showed that a significantly lower level of miR­223­3p was present in the HCC tissues, compared with that in non­cancerous tissues (P<0.05). In addition, five GEO data sets revealed diagnostic values of miR­223­3p, with an area under the curve (AUC) of >0.80 (P<0.05). The diagnostic accuracy of the precursor miR­223 in TCGA was also calculated (AUC=0.78, P<0.05). Similarly, the precursor miR­223 showed a higher level of downregulation in HCC tissues, compared with that in healthy controls in TCGA (P<0.001). A summary ROC was also calculated as 0.89 (95% CI, 0.85­0.91) in the meta­analysis. A total of 72 potential targets were extracted, mainly involved in the terms 'microRNAs in cancer', 'ATP binding' and 'prostate cancer'. Five potential target genes were considered the hub genes of miR­223­3p in HCC, including checkpoint kinase 1, DNA methyltransferase 1, baculoviral IAP repeat containing 5, kinesin family member 23, and collagen, type I, α1. Based on TCGA, the hub genes were significantly upregulated in HCC (P<0.05). Collectively, these results showed that miR­223­3p may be crucial in HCC carcinogenesis showing high diagnostic accuracy, and may be mediated by several hub genes.

Potential Targets and Clinical Value of MiR-224-5p in Cancers of the Digestive Tract.

BACKGROUND/AIMS: MicroRNAs participate in various biological processes in malignant tumors. However, the mechanisms of miR-224-5p in digestive system cancers are not fully understood. A comprehensive investigation of the clinical value and potential targets of miR-224-5p in cancers of the digestive tract is necessary. METHODS: Expression profiling data and related-prognostic data of miR-224-5p were acquired from Gene Expression Omnibus, The Cancer Genome Atlas, ArrayExpress, and published literature. The potential target mRNAs of miR-224-5p were predicted using bioinformatics methods and finally annotated using Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. RESULTS: MiR-224-5p is up-regulated in digestive system cancers (SMD=0.69, 95% CI: 0.43-0.96, P<0.0001) and exhibits a moderate diagnostic ability (AUC=0.84, 95% CI: 0.80-0.87). Our data also demonstrated that miR-224-5p is statistically significantly correlated with overall survival univariate analysis (HR=1.69, 95% CI: 1.15-2.49, P=0.007) and multivariate analysis (HR=2.39, 95% CI: 1.74-3.30, P<0.0001). In total, 388 potential miR-224-5p target mRNAs were predicted by bioinformatics methods. GO annotation analysis revealed that the top terms of miR-224-5p in biological process, cellular component and molecular function were system development, neuron part, and transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding, respectively. Moreover, eight pathways were identified in KEGG pathway enrichment analysis. CONCLUSIONS: MiR-224-5p is up-regulated and has the potential to become a diagnostic and prognostic biomarker in digestive system cancers. MiR-224-5p might play vital roles in cancers of the digestive tract but the exact molecular mechanisms need further study and verification.

Identification of miR-101-3p targets and functional features based on bioinformatics, meta-analysis and experimental verification in hepatocellular carcinoma.

BACKGROUND: MiR-101-3p has been reported to suppress invasion and metastasis in hepatocellular carcinoma (HCC) cells. However, the relevant mechanisms are still unclear. The research seeks to determine systematic value of miR-101-3p in HCC, and comprehensively summarize the predicted target genes as well as their potential function, pathways and networks in HCC. METHODS: The miR-101-1 profiles in 353 HCC patients from The Cancer Genome Atlas (TCGA) were analyzed. Meta-analysis was performed to estimate relationship of miR-101 (including precursor and mature miR-101) with clinical features and prognosis in HCC. Further, the promising targets of miR-101-3p were predicted and followed with Gene Ontology (GO), pathway and network analysis. In addition, the functional impact of miR-101-3p was confirmed with in vitro experiments in HCC cells. RESULTS: In TCGA data, low-expression of miR-101-1 might be a diagnostic (AUC: 0.924, 95% CI: 0.894-0.953) and prognostic (HR=1.55) marker for HCC. Down-regulated miR-101-1 also correlated with poor differentiation, advanced TNM stage, lymph node metastasis and high AFP level of HCC. Meta-analysis revealed that miR-101 down-regulation were associated with poor prognosis, high AFP level and advanced TNM stage of HCC. Moreover, 343 hub genes were filtered and miR-101-3p may be involved in intracellular signaling cascade, transcription, metabolism and cell proliferation. Focal adhesion and pathways in cancer were also significantly enriched. In vitro experiments demonstrated that miR-101-3p inhibited proliferation and promoted apoptosis in HCC cells. CONCLUSIONS: MiR-101-1 may be a prospective biomarker for diagnosis and prognosis of HCC. Potential targets of miR-101-3p could regulate genesis and development of HCC. The data offers insights into biological significances and promising targets of miR-101-3p for further investigation and potential therapies in HCC.

miR-204 regulates the biological behavior of breast cancer MCF-7 cells by directly targeting FOXA1.

MicroRNAs (miRNAs) are short, non-protein-coding RNAs and transcripts that are 18-24 nt in length. miR-204 was first identified as an anti-oncogene and is reported to be downregulated in non-small cell lung cancer, glioma, gastric and thyroid cancer. Recent studies have proposed that a low level of miR-204 expression is associated with tumor progression and disease outcome in breast cancer. Forkhead box A1 (FOXA1), a transcription factor, plays a crucial role in breast cancer and has been predicted as a target of miR-204. In the present study, we integrated the results of microarray analyses of breast cancer tissues obtained from an online database with our own determination of the expression of miR-204 in breast cancer MCF-7 cells using real-time qPCR (RT-qPCR). The proliferative capacity of the cells was assessed using MTT assays, and cell mobility and invasiveness were evaluated using cell migration and invasion assays, respectively. Flow cytometry was used to analyze apoptosis. FOXA1 levels were detected using RT-qPCR and western blot analysis. Luciferase assays were performed to confirm that FOXA1 is directly targeted by miR-204. The results showed that miR-204 was downregulated in breast cancer cells, and we found that miR-204 was expressed at a lower level in MCF-7 cells than that observed in normal breast epithelial HBL-100 cells. Overexpression of miR-204 inhibited cell proliferation, migration and invasion and promoted apoptosis. Western blot analysis revealed that the expression of FOXA1 at the protein level was significantly reduced after cells were transfected with miR-204-expressing viruses. Luciferase assays demonstrated that FOXA1 is a direct target of miR-204, which binds to FOXA1 in a complementary region. In conclusion, miR-204 regulates the biological behavior of breast cancer cells, including cell proliferation, invasion, metastasis and apoptosis, by directly targeting FOXA1. Thus, miR-204 may act as a tumor-suppressor, and the results of the present study provide a reference for future research into the potential mechanisms underlying breast cancer progression.

Clinical value and potential targets of miR-224-5p in hepatocellular carcinoma validated by a TCGA- and GEO- based study.

OBJECTIVE: to explore clinical value and potential targets of MicroRNA-224-5p in the tumorigenesis and progression of hepatocellular carcinoma (HCC). METHODS: We evaluated the clinical value of MicroRNA-224-5p from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Meanwhile, target genes of MicroRNA-224-5p were predicted by bioinformatics method. The target genes of MicroRNA-224-5p were finally analyzed in Gene Ontology (GO) terms, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation, and Protein-Protein Interaction (PPI) network annotation. RESULTS: MicroRNA-224-5p expression level in HCC was higher than in non-tumor tissues (SMD=1.24; 95% CI, 0.68 to 1.81; P<0.0001) and MicroRNA-224-5p might represent a diagnostic marker (overall AUC=0.92; 95% CI, 0.90 to 0.94). 262 target genes were acquired by overlapping 4927 genes predicted by more than four computational prediction tools with 1,123 down-regulated DEGs in HCC. Furthermore, gene sets enrichment analysis of the 262 overlapping genes was implemented. The mostly significant GO terms within the overlapping target genes of MicroRNA-224-5p were cellular response to chemical stimulus, plasma membrane part and coenzyme binding. KEGG pathway annotation showed the overlapping genes mostly took part in metabolic pathways. In PPI analysis, one hub gene, GNA14, stood out cause for the significant negative correlation with MicroRNA-224. CONCLUSION: MicroRNA-224-5p is upregulated in HCC and may be a prospective biomarker for diagnosis. Moreover, MicroRNA-224-5p might play an oncogenic role in HCC by targeting GNA14.

Tetraploidy/near-tetraploidy acute myeloid leukemia.

A tetraploid/near tetraploid (T/NT) karyotype is a rare finding in acute myeloid leukemia (AML). Here we report 38 AML patients with a T/NT karyotype, including 26 men and 12 women with a median age of 65 years. T/NT karyotype was detected at initial diagnosis of AML in 16 patients, and acquired during the course of disease in 22 patients. All patients showed large blasts with frequent prominent nucleoli, cytoplasmic vacuoles and/or inclusions, nuclear irregularity and/or budding. Eleven patients had a non-complex and 27 had a complex T/NT karyotype; 21 patients also had pseudodiploid and/or triploid clones. After T/NT karyotype detection, 32 patients received chemotherapy and 10 also received stem cell transplant. After a median of 6.2 months follow-up, 32 patients died of disease or complications, 5 were alive with complete remission, and 1 alive with persistent AML. Median overall survival (OS) was 5 months. Patients with a non-complex T/NT karyotype had a significantly superior OS compared to those with a complex T/NT karyotype (10.7 vs. 3.4 months, p=0.0280). We conclude that T/NT karyotype in AML is often associated with distinctive morphologic features and conveys generally poor outcomes. Distinction of complex versus non-complex T/NT karyotype provides further prognostic information.

Well-differentiated systemic mastocytosis showed excellent clinical response to imatinib in the absence of known molecular genetic abnormalities: A case report.

INTRODUCTION: Well-differentiated systemic mastocytosis (WDSM) is a rare, recently recognized provisional subvariant of systemic mastocytosis (SM). We report a case of WDSM that showed excellent clinical and cutaneous response to imatinib in the absence of known molecular genetic abnormalities. CLINICAL FINDINGS/DIAGNOSES: We present a 24-year-old woman with childhood onset of skin manifestations that progressed to mediator-related systemic events, and a gastrointestinal tract mastocytoma. A subsequent bone marrow examination showed WDSM. Treatment with imatinib resulted in complete resolution of cutaneous lesions and systemic symptoms, which relapsed with the discontinuation of the drug. Targeted next-generation sequencing-based mutation analysis did not demonstrate any mutations in the coding regions of KIT or other genes commonly associated with myeloid neoplasms. CONCLUSIONS: The diagnosis of WDSM is challenging in the absence of spindle-shaped mast cells, CD2 or CD25 expression, and KIT D816 mutation. This case illustrated the need for recognizing this unique variant of SM for diagnostic and therapeutic implications.

Prognostic Values of Vimentin Expression and Its Clinicopathological Significance in Non-Small Cell Lung Cancer: A Meta-Analysis of Observational Studies with 4118 Cases.

BACKGROUND: Vimentin is a member of the intermediate filament proteins and a canonical marker of the epithelial-mesenchymal transition (EMT), which is pivotal in tumorigenesis, metastasis and invasion in non-small cell lung cancer (NSCLC). The current meta-analysis aimed to investigate the associations between vimentin and prognosis and progression in NSCLC. METHODS: Databases with literature published in English, including PubMed, Web of Science, Embase, Science Direct, Wiley Online Library, Ovid, Cochrane Central Register of Controlled Trials, LILACS and Google Scholar, and the CNKI, VIP, CBM and WanFang databases in Chinese were used for the literature search. The key terms included (1) 'vimentin' OR 'vim' OR 'vmt' OR 'vm' OR 'hel113' OR 'ctrct30' and (2) 'pulmon*' OR 'lung' OR 'alveolar' and (3) 'cancer' OR 'carcinoma' OR 'tumor' OR 'adenocarcinoma' OR 'squamous' OR 'neoplas*' OR 'malignan*'. The data were combined by random effect model and the H value and I2 were used to assess the heterogeneity. All the meta-analysis was conducted using Stata 12.0. RESULTS: Thirty-two qualified studies (4118 cases) were included in the current meta-analysis. Twelve studies with 1750 patients were included to assess the significance of vimentin in the overall survival (OS) of NSCLC; the pooled hazard ratio (HR) was 1.831 (confidence interval (CI): 1.315-2.550, P<0.001) in the univariate analysis and 1.266 (CI: 0.906-1.768, P = 0.167) in the multivariate analysis. Four studies with 988 cases were applicable to determine the significance of vimentin in the disease-free survival (DFS) of NSCLC; the pooled HR of the DFS was 1.224 (CI: 0.921-1.628, P = 0.164) in the univariate analysis and 1.254 (CI: 0.985-1.956, P = 0.067) in the multivariate analysis. Regarding the relationships between vimentin and clinicopathological factors, the pooled odds ratio (OR) with 3406 NSCLCs indicated that up-regulated vimentin was associated with smoking (OR = 1.359, CI: 1.098-1.683, P = 0.004), poor differentiation (OR = 2.133, CI: 1.664-2.735, P<0.001), an advanced TNM stage (OR = 3.275, CI: 1.987-5.397, P<0.001), vascular invasion (OR = 3.492, CI: 1.063-11.472, P = 0.039), lymph node metastasis (OR = 2.628, CI: 1.857-3.718, P<0.001), recurrence (OR = 1.631, CI: 1.052-2.528, P = 0.029) and pleural invasion (OR = 2.346, CI: 1.397-3.941, P = 0.001). There was no significant correlation between vimentin and age, gender, diameter, T stage, distant metastasis, or marginal invasion (P>0.05). CONCLUSION: An overexpression of vimentin may predict the progression and an unfavorable survival of NSCLC. Vimentin may represent a helpful biomarker and a potential target for the treatment strategies of NSCLC. Additional, prospective studies with large samples are necessary to confirm the significance of vimentin in NSCLC.

Cytogenetic Evolution Associated With Disease Progression in Hematopoietic Neoplasms With t(8;22)(p11;q11)/BCR-FGFR1 Rearrangement.

Hematopoietic neoplasms with FGFR1 rearrangements are rare. Clinically, patients often present with a chronic myeloproliferative neoplasm with eosinophilia and an increased risk of transformation to acute leukemia. We report a patient who initially presented with B-cell acute lymphoblastic leukemia (B-ALL) with t(8;22)(p11.2;q11.2) and an additional derivative chromosome 22 [der(22)t(8;22)]. After induction chemotherapy, B-ALL blasts were eradicated; however, a chronic myeloproliferative process emerged showing persistent t(8;22) (p11.2;q11.2) but not der(22)t(8;22). Combined morphologic and fluorescence in situ hybridization revealed that both lymphoblasts and myeloid cells harbored t(8;22)(p11.2;q11.2); but only lymphoblasts carried the additional der(22)t(8;22). This case provides direct evidence to illustrate the clonal relationship of chronic phase and blast phase in myeloid neoplasms with FGFR1 rearrangement, and demonstrates that clonal cytogenetic evolution plays an important role in disease progression.

High Ki-67 Immunohistochemical Reactivity Correlates With Poor Prognosis in Bladder Carcinoma: A Comprehensive Meta-Analysis with 13,053 Patients Involved.

Ki-67 is considered as one of prime biomarkers to reflect cell proliferation and immunohistochemical Ki-67 staining has been widely applied in clinical pathology. To solve the widespread controversy whether Ki-67 reactivity significantly predicts clinical prognosis of bladder carcinoma (BC), we performed a comprehensive meta-analysis by combining results from different literature. A comprehensive search was conducted in the Chinese databases of WanFang, China National Knowledge Infrastructure and Chinese VIP as well as English databases of PubMed, ISI web of science, EMBASE, Science Direct, and Wiley online library. Independent studies linking Ki-67 to cancer-specific survival (CSS), disease-free survival (DFS), overall survival (OS), progression-free survival (PFS), and recurrence-free survival (RFS) were included in our meta-analysis. With the cut-off values literature provided, hazard ratio (HR) values between the survival distributions were extracted and later combined with STATA 12.0. In total, 76 studies (n = 13,053 patients) were eligible for the meta-analysis. It was indicated in either univariate or multivariate analysis for survival that high Ki-67 reactivity significantly predicted poor prognosis. In the univariate analysis, the combined HR for CSS, DFS, OS, PFS, and RFS were 2.588 (95% confidence interval [CI]: 1.623-4.127, P < 0.001), 2.697 (95%CI: 1.874-3.883, P < 0.001), 2.649 (95%CI: 1.632-4.300, P < 0.001), 3.506 (95%CI: 2.231-5.508, P < 0.001), and 1.792 (95%CI: 1.409-2.279, P < 0.001), respectively. The pooled HR of multivariate analysis for CSS, DFS, OS, PFS, and RFS were 1.868 (95%CI: 1.343-2.597, P < 0.001), 2.626 (95%CI: 2.089-3.301, P < 0.001), 1.104 (95%CI: 1.008-1.209, P = 0.032), 1.518 (95%CI: 1.299-1.773, P < 0.001), and 1.294 (95%CI: 1.203-1.392, P < 0.001), respectively. Subgroup analysis of univariate analysis by origin showed that Ki-67 reactivity significantly correlated with all 5 clinical outcome in Asian and European-American patients (P < 0.05). For multivariate analysis, however, the pooled results were only significant for DFS, OS, and RFS in Asian patients, for CSS, DFS, PFS, and RFS in European-American patients (P < 0.05). In the subgroup with low cut-off value (<20%), our meta-analysis indicated that high Ki-67 reactivity was significantly correlated with worsened CSS, DFS, OS, PFS, and RFS on univariate analysis (P < 0.05). For multivariate analysis, the meta-analysis of literature with low cut-off value (<20%) demonstrated that high Ki-67 reactivity predicted shorter DFS, PFS, and RFS in BC patients (P < 0.05). In the subgroup analysis of high cut-off value (≥20%), our meta-analysis indicated that high Ki-67 reactivity, in either univariate or multivariate analysis, significantly correlated with all five clinical outcomes in BC patients (P < 0.05). The meta-analysis indicates that high Ki-67 reactivity significantly correlates with deteriorated clinical outcomes in BC patients and that Ki-67 can be considered as an independent indicator for the prognosis by the meta-analyses of multivariate analysis.