EML4-ALK fusion protein in Lung cancer cells enhances venous thrombogenicity through the pERK1/2-AP-1-tissue factor axis.

BACKGROUND: Accumulating evidence links the echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) rearrangement to venous thromboembolism (VTE) in non-small cell lung cancer (NSCLC) patients. However, the corresponding mechanisms remain unclear. METHOD: High-throughput sequencing analysis of H3122 human ALK-positive NSCLC cells treated with ALK inhibitor/ dimethyl sulfoxide (DMSO) was performed to identify coagulation-associated differential genes between EML4-ALK fusion protein inhibited cells and control cells. Sequentially, we confirmed its expression in NSCLC patients' tissues and in the plasma of a subcutaneous xenograft mouse model. An inferior vena cava (IVC) ligation model was used to assess clot formation potential. Additionally, pathways involved in tissue factor (TF) regulation were explored in ALK-positive cell lines H3122 and H2228. Statistical significance was determined by Student t-test and one-way ANOVA using SPSS. RESULTS: Sequencing analysis identified a significant downregulation of TF after inhibiting EML4-ALK fusion protein activity in H3122 cells. In clinical NSCLC cases, TF expression was increased especially in ALK-positive NSCLC tissues. Meanwhile, H3122 and H2228 with high TF expression exhibited shorter plasma clotting time and higher TF activity versus ALK-negative H1299 and A549 in cell culture supernatant. Mice bearing H2228 tumor showed a higher concentration of tumor-derived TF and TF activity in plasma and the highest adjusted IVC clot weights. Limiting EML4-ALK protein phosphorylation downregulated extracellular regulated protein kinases 1/2 (ERK1/2)-activating the protein-1(AP-1) signaling pathway and thus attenuated TF expression. CONCLUSION: EML4-ALK fusion protein may enhance venous thrombogenicity by regulating coagulation factor TF expression. There was potential involvement of the pERK1/2-AP-1 pathway in this process.

Resection of rectal metastasis after previous radical surgery for pancreatic cancer: Case report and literature review.

RATIONALE: Pancreatic ductal adenocarcinoma (PDAC) is the main type of pancreatic cancer with a poor prognosis. Rectal metastasis after radical resection of PDAC is comparatively rare, and the understanding of such cases is currently not unified. This study presents the entire process of diagnosis and treatment of a patient with PDAC metastasized to the rectal. We propose the viewpoint of exploring potential biomarkers or establishing effective predictive models to assist in the clinical decision-making of such cases. PATIENT CONCERNS: We present the case of a 71-year-old man with slight abdominal distension and dull pain. He underwent surgical treatment for a malignant tumor of the pancreatic body, which was discovered through computed tomography and magnetic resonance imaging examinations. Nine months after the pancreatectomy, a rectal mass was identified by digital rectal examination and diagnosed as a malignant lesion through a puncture biopsy. After a multidisciplinary joint consultation, the patient underwent radical surgery. It was later confirmed as rectal adenocarcinoma based on postoperative pathological results. DIAGNOSIS: The pathological result after pancreatic surgery was PDAC, which had invaded the peripheral nerves and abdominal arteries. A diagnosis of rectal metastasis was determined ultimately by combining with the medical history and immunohistochemical staining results. INTERVENTIONS AND OUTCOMES: Treatment of the PDAC included laparoscopic resection of the body and tail of the pancreas combined with splenectomy, and postoperative systemic chemotherapy. In addition, treatment of the rectal metastasis included laparoscopic radical resection and postoperative systemic chemotherapy. The patient's current living condition was good. LESSONS: As a rare metastatic site of PDAC, rectal metastasis should be avoided because of misdiagnosis and missed diagnosis. Surgical resection is still an effective treatment strategy for localized pancreatic tumors and isolated metastases. Furthermore, the mining of potential biomarkers or the establishment of predictive models for pancreatic cancer and its metastases may contribute to better clinical decision-making in the future.

[Terpinen-4-ol inhibits proliferation of VSMCs exposed to high glucose via regulating KLF4/NF-κB signaling pathway].

This study aimed to observe the effect of terpinen-4-ol(T4O) on the proliferation of vascular smooth muscle cells(VSMCs) exposed to high glucose(HG) and reveal the mechanism via the Krüppel-like factor 4(KLF4)/nuclear factor kappaB(NF-κB) signaling pathway. The VSMCs were first incubated with T4O for 2 h and then cultured with HG for 48 h to establish the model of inflammatory injury. The proliferation, cell cycle, and migration rate of VSMCs were examined by MTT method, flow cytometry, and wound healing assay, respectively. The content of inflammatory cytokines including interleukin(IL)-6 and tumor necrosis factor-alpha(TNF-α) in the supernatant of VSMCs was measured by enzyme-linked immunosorbent assay(ELISA). Western blot was employed to determine the protein levels of proliferating cell nuclear antigen(PCNA), Cyclin D1, KLF4, NF-κB p-p65/NF-κB p65, IL-1ß, and IL-18. The KLF4 expression in VSMCs was silenced by the siRNA technology, and then the effects of T4O on the cell cycle and protein expression of the HG-induced VSMCs were observed. The results showed that different doses of T4O inhibited the HG-induced proliferation and migration of VSMCs, increased the percentage of cells in G_1 phase, and decreased the percentage of cells in S phase, and down-regulated the protein levels of PCNA and Cyclin D1. In addition, T4O reduced the HG-induced secretion and release of the inflammatory cytokines IL-6 and TNF-α and down-regulated the expression of KLF4, NF-κB p-p65/NF-κB p65, IL-1ß, and IL-18. Compared with si-NC+HG, siKLF4+HG increased the percentage of cells in G_1 phase, decreased the percentage of cells in S phase, down-regulated the expression of PCNA, Cyclin D1, and KLF4, and inhibited the activation of NF-κB signaling pathway. Notably, the combination of silencing KLF4 with T4O treatment further promoted the changes in the above indicators. The results indicate that T4O may inhibit the HG-induced proliferation and migration of VSMCs by down-regulating the level of KLF4 and inhibiting the activation of NF-κB signaling pathway.

Inflammatory pseudotumor-like follicular dendritic cell sarcoma with first clinical manifestation of thrombocytopenia: A case report.

BACKGROUND: Inflammatory pseudotumor-like follicular dendritic cell sarcoma (IPT-like FDCS) is often associated with Epstein-Barr (EB) virus infection. The tumor is commonly found in the spleen and liver, and it has been reported in the literature that it can be associated with paraneoplastic pemphigus, myasthenia gravis, and other diseases. A case of IPT-like FDCS with clinical features of thrombocytopenia has not been reported. PATIENT CONCERNS: A 59-year-old male patient visited our hospital in September 2020 due to bleeding gums and epistaxis. DIAGNOSIS: Splenic lymphoma with marked thrombocytopenia was initially diagnosed. The patient underwent pathological examination after splenectomy. Microscopic examination showed spindle-shaped or oval cells arranged in loose bundles, a large number of lymphocytes and plasma cells infiltrating the interstitium, and fibrin-like changes in the blood vessel wall. Immunohistochemical detection of tumor cells was positive for CD21, CD35, and Epstein-Barr virus in situ hybridization, and the patient was diagnosed with IPT-like FDCS. INTERVENTIONS: The patient underwent a splenectomy. The patient received platelet-raising therapy postoperatively. OUTCOMES: No tumor recurrence or metastasis was found during the 17-month follow-up period, and the platelet count returned to normal. CONCLUSION: IPT-like FDCS is an uncommon tumor, and its first presentation with marked thrombocytopenia is even rarer. The tumor was clinically and radiographically nonspecific. Definitive diagnosis relies on histopathological and immunohistochemical staining. IPT-like FDCS is biologically indolent and has a favorable prognosis.

Detection significance of miR-3662, miR-146a, and miR-1290 in serum exosomes of breast cancer patients.

CONTEXT: The potential relationship between exosomal microRNAs (miRNAs) and clinical symptoms in breast cancer patients and the expression levels of exosomal miRNAs in patients undergoing surgery and chemotherapy are still unclear. AIMS: The aim of this study was to explore the correlation among exosomal miRNAs and clinical features and treatment in breast cancer patients. MATERIALS AND METHODS: First, exosomes were isolated from the serum of patients with breast cancer and healthy controls. Next, the features of exosomes were identified by transmission electron microscopy, nanoparticle tracking analysis, and Western blot assays. Then, we detected the expression of the top-ranked miRNAs (miR-3662, miR-16-1, miR-146a, miR-1290, and miR-29c) in sixty breast cancer patients and twenty healthy controls using quantitative real-time polymerase chain reaction. STATISTICAL ANALYSIS USED: The differential expression was measured by the Mann-Whitney U-test. RESULTS: The relative expression of miR-3662, miR-146a, and miR-1290 in serum exosomes was significantly higher in patients than healthy controls. Moreover, significant differences were found in the lymph node metastasis and clinical stage of breast cancer as the miRNA levels changed, but their expression levels in exosomes and sera were not correlated. In addition, exosomal miR-3662, miR-146a, and miR-1290 were shown to be valuable biomarkers to monitor patient condition in the course of surgery and chemotherapy. CONCLUSIONS: Exosomal miR-3662, miR-146a, and miR-1290 may have promising predictive value and could be utilized as biomarkers for diagnosis and preventative strategy development.

Identification of common signatures in idiopathic pulmonary fibrosis and lung cancer using gene expression modeling.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is associated with an increased risk for lung cancer, but the underlying mechanisms driving malignant transformation remain largely unknown. This study aimed to identify differentially expressed genes (DEGs) distinguishing IPF and lung cancer from healthy individuals and common genes driving the transformation from healthy to IPF and lung cancer. METHODS: The gene expression data for IPF and non-small cell lung cancer (NSCLC) were retrieved from the Gene Expression Omnibus (GEO) database. The DEG signatures were identified via unsupervised two-way clustering (TWC) analysis, supervised support vector machine analysis, dimensional reduction, and mutual exclusivity analysis. Gene enrichment and pathway analyses were performed to identify common signaling pathways. The most significant signature genes in common among IPF and lung cancer were further verified by immunohistochemistry. RESULTS: The gene expression data from GSE24206 and GSE18842 were merged into a super array dataset comprising 86 patients with lung disorders (17 IPF and 46 NSCLC) and 51 healthy controls and measuring 23,494 unique genes. Seventy-nine signature DEGs were found among IPF and NSCLC. The peroxisome proliferator-activated receptor (PPAR) signaling pathway was the most enriched pathway associated with lung disorders, and matrix metalloproteinase-1 (MMP-1) in this pathway was mutually exclusive with several genes in IPF and NSCLC. Subsequent immunohistochemical analysis verified enhanced MMP1 expression in NSCLC associated with IPF. CONCLUSIONS: For the first time, we defined common signature genes for IPF and NSCLC. The mutually exclusive sets of genes were potential drivers for IPF and NSCLC.

HYAL1 Is Downregulated in Idiopathic Pulmonary Fibrosis and Inhibits HFL-1 Fibroblast Proliferation When Upregulated.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF), the most common interstitial lung disease, arises from transforming growth factor beta 1- (TGFß1-) induced aberrant fibroproliferation in response to epithelial injury. The TGFß1-) induced aberrant fibroproliferation in response to epithelial injury. The TGF. METHODS: We first performed microarray data mining of previously published gene expression datasets to identify key gene signatures in IPF lung tissues. HYAL1 expression levels in IPF and normal lung tissues were then characterized using immunohistochemistry followed by real-time quantitative reverse transcription-PCR (qRT-PCR) and western blot analysis on isolated fibroblasts from fresh lung tissues of IPF and healthy donors. A human fetal lung fibroblast HFL-1 cell line, which was used in place of primary lung fibroblasts, was used to assess the proliferative or apoptotic effects associated with lentiviral-induced HYAL1 overexpression using CCK-8 cell proliferation assay and Annexin V-APC staining. The identification of potentially associated molecular pathways was performed using microarray analysis followed by qRT-PCR and western blot analysis. RESULTS: Lung tissue microarray data mining and immunohistochemistry revealed significantly downregulation of HYAL1 in IPF lung tissue. However, HYAL1 in IPF lung tissue. However, HYAL1 in IPF lung tissue. However, HYAL1 in IPF lung tissue. However, ß1-) induced aberrant fibroproliferation in response to epithelial injury. The TGFß1-) induced aberrant fibroproliferation in response to epithelial injury. The TGF. CONCLUSIONS: We showed that HYAL1 overexpression could prevent HFL-1 fibroproliferation. Furthermore, our findings suggest that transcriptional regulators and BMP receptor signaling may be involved in HYAL1 modulation in IPF therapy.HYAL1 in IPF lung tissue. However.

In silico analysis identifies CRISP3 as a potential peripheral blood biomarker for multiple myeloma: From data modeling to validation with RT-PCR.

Octamer-binding protein 2 (Oct2) binds to the ATGCAAAT octamer on the IgH enhancer and stimulates IgH expression in human multiple myeloma (MM). Cysteine-rich secreted protein 3 (CRISP3) possesses the ATGCAAAT sequence and thus is activated by Oct2 in mouse B cells, suggesting that CRISP3 may be activated in and be a potential biomarker for MM. The present study involved a meta-analysis of the gene expression profiling data of human MM peripheral blood. Significantly expressed genes were analyzed on merged super array microarray data and selected sample data with significantly expressed genes were additionally analyzed by principal component analysis and Bayesian probit regression. CRISP3, Oct2, Apha-1B-glycoprotein (A1GB) and Cyclin D2 (CCND2) were validated in clinical MM peripheral blood samples using reverse transcription quantitative polymerase chain reaction. In the gene expression profiling data, CRISP3 was significantly upregulated and had certain proportions on the discriminated principal component of significantly expressed gene sample data. RT-qPCR analysis revealed CRISP3 was significantly upregulated in MM. Therefore, CRISP3 is a potential peripheral blood biomarker for MM.

DNA methylation signatures of pulmonary arterial smooth muscle cells in chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening disease, which is often underpinned by vascular remodeling. Pulmonary arterial smooth muscle cells (PASMCs) are the main participants in vascular remodeling. However, their biological role in CTEPH is not entirely clear. In the present study, we analyzed the whole epigenome-wide DNA methylation profile of cultured PASMCs from CTEPH and control cell lines with the Illumina Human Methylation 450K BeadChip. A total of 6,829 significantly differentially methylated probes (DMPs) were detected between these two groups. Among these, 4,246 DMPs were hypermethylated, while 2,583 DMPs were hypomethylated. The functional enrichment analysis of 1,743 DMPs in the promoter regions and corresponding genes indicated that DNA hypermethylation and hypomethylation might be involved in the regulation of genes that have multifarious biological roles, including roles in cancer-related diseases, the regulation of the actin cytoskeleton, cell adhesion, and pattern specification processes. The observed methylations were categorized into the most important functions, including those involved in cell proliferation, immunity, and migration. We speculate that these methylations were most likely involved in the possible pathophysiology of CTEPH. Gene interaction analysis pertaining to signal networks confirmed that PIK3CA and PIK3R1 were important mediators in these whole networks. The mRNA levels of PIK3CA, HIC1, and SSH1 were verified by qPCR and corresponded with DNA methylation differences. Understanding epigenetic features associated with CTEPH may provide new insights into the mechanism that underlie this condition.

Microarray Analysis and Detection of MicroRNAs Associated with Chronic Thromboembolic Pulmonary Hypertension.

The aim of this study was to understand the importance of chronic thromboembolic pulmonary hypertension- (CTEPH-) associated microRNAs (miRNAs). miRNAs differentially expressed in CTEPH samples compared with control samples were identified, and the target genes were predicted. The target genes of the key differentially expressed miRNAs were analyzed, and functional enrichment analyses were carried out. Finally, the miRNAs were detected using RT-PCR. Among the downregulated miRNAs, MiR-3148 regulated the most target genes and was significantly enriched in pathways in cancer, glioma, and ErbB signaling pathway. Furthermore, the number of target genes coregulated by miR-3148 and other miRNAs was the most. AR (androgen receptor), a target gene of hsa-miR-3148, was enriched in pathways in cancer. PRKCA (Protein Kinase C Alpha), also a target gene of hsa-miR-3148, was enriched in 15 of 16 KEGG pathways, such as pathways in cancer, glioma, and ErbB signaling pathway. In addition, the RT-PCR results showed that the expression of hsa-miR-3148 in CTEPH samples was significantly lower than that in control samples (P < 0.01). MiR-3148 may play an important role in the development of CTEPH. The key mechanisms for this miRNA may be hsa-miR-3148-AR-pathways in cancer or hsa-miR-3148-PRKCA-pathways in cancer/glioma/ErbB signaling pathway.

MicroRNA-29c Prevents Pulmonary Fibrosis by Regulating Epithelial Cell Renewal and Apoptosis.

Successful repair and renewal of alveolar epithelial cells (AECs) are critical in prohibiting the accumulation of myofibroblasts in pulmonary fibrogenesis. MicroRNAs (miRNAs) are multifocal regulators involved in lung injury and repair. However, the contribution of miRNAs to AEC2 renewal and apoptosis is incompletely understood. We report that miRNA-29c (miR-29c) expression is lower in AEC2s of individuals with idiopathic pulmonary fibrosis than in healthy lungs. Epithelial cells overexpressing miR-29c show higher proliferative rates and viability. miR-29c protects epithelial cells from apoptosis by targeting forkhead box O3a (Foxo3a). Both overexpression of miR-29c conventionally and AEC2s specifically lead to less fibrosis and better recovery in vivo. Furthermore, deficiency of miR-29c in AEC2s results in higher apoptosis and reduced epithelial renewal. Interestingly, a gene network including a subset of apoptotic genes was coregulated by both Toll-like receptor 4 and miR-29c. Taken together, miR-29c maintains epithelial integrity and promotes recovery from lung injury, thereby attenuating lung fibrosis in mice.

Microarray expression profile of circular RNAs in chronic thromboembolic pulmonary hypertension.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare but debilitating and life-threatening complication of acute pulmonary embolism. Circular RNAs (circRNAs), presenting as covalently closed continuous loops, are RNA molecules with covalently joined 3'- and 5'-ends formed by back-splicing events. circRNAs may be significant biological molecules to understand disease mechanisms and to identify biomarkers for disease diagnosis and therapy. The aim of this study was to investigate the potential roles of circRNAs in CTEPH. METHODS: Ten human blood samples (5 each from CTEPH and control groups) were included in the Agilent circRNA chip. The differentially expressed circRNAs were evaluated using t test, with significance set at a P value of < .05. A functional enrichment analysis for differentially expressed circRNAs was performed using DAVID online tools, and a Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis for target genes of miRNAs was performed using the R package clusterProfiler. Furthermore, miRNAs that interacted with differentially expressed circRNAs were predicted using the miRanda package. mRNAs that had clear biological functions and were regulated by miRNAs were predicted using miRWalk2.0 and then combined into a circRNA-miRNA-mRNA network. RESULTS: In total, 351 differentially expressed circRNAs (122 upregulated and 229 downregulated) between CTEPH and control groups were obtained; among these circRNAs, hsa_circ_0002062 and hsa_circ_0022342 might be important because they can regulate 761 (e.g., hsa-miR-942-5p) and 453 (e.g., hsa-miR-940) miRNAs, respectively. Target genes (e.g., cyclin-dependent kinase 6) of hsa-miR-942-5p were mainly enriched in cancer-related pathways, whereas target genes (e.g., CRK-Like Proto-Oncogene, Adaptor Protein) of hsa-miR-940 were enriched in the ErbB signaling pathway. Therefore, these pathways are potentially important in CTEPH. CONCLUSIONS: Our findings suggested that hsa_circ_0002062 and hsa_circ_0022342 may be key circRNAs for CTEPH development and that their targeted regulation may be an effective approach for treating CTEPH.

miR-130b-3p Modulates Epithelial-Mesenchymal Crosstalk in Lung Fibrosis by Targeting IGF-1.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and usually lethal fibrotic lung disease with largely unknown etiology and pathogenesis. Evidence suggests microRNAs (miRNA) contribute to pathogenesis of IPF. In this study, we sought to identify miRNA expression signatures and determine the role of miR-130b-3p in lung fibrosis. The miRNA expression profile of the lungs from patients with IPF and normal donors was determined by Affymetrix microarray, and transcriptome with Affymetrix array. The functions and signal pathways as well as miRNA-mRNA networks were established by bioinformatics analysis. Luciferase assays and ELISA were used to confirm the miRNA target gene. The effect of miRNA-transfected epithelium on fibroblast activities was assessed using a co-culture system. The fibroblast activities were determined by qRT-PCR, western blotting, Transwell and BrdU assays. Seven miRNAs were significantly decreased in IPF lungs, with miR-130b-3p being the highest in the miRNA-mRNA network. Insulin-like growth factor (IGF-1) was a target gene of miR-130b-3p in the epithelium. miR-130b-3p inhibition in the epithelium induced collagen I expression and enhanced the proliferation and migration ability of fibroblast in co-culture systems, which mimicked the functions of exogenous IGF-1 on fibroblasts. Neutralizing IGF-1 with an antibody significantly reduced the modulatory effects of miR-130b-3p inhibitor-transfected epithelium on the activation of fibroblasts. Our results show that miR-130b-3p was downregulated in IPF lungs. miR-130b-3p downregulation contributed to the activation of fibroblasts and the dysregulated epithelial-mesenchymal crosstalk by promoting IGF-1 secretion from lung epithelium, suggesting a key regulatory role for this miRNA in preventing lung fibrosis.

G protein-coupled receptor 56 regulates matrix production and motility of lung fibroblasts.

Idiopathic pulmonary fibrosis is a chronic, progressive, and fatal fibrotic lung disease with a poor prognosis, but no effective treatment is available. G protein-coupled receptor 56 (GPR56) plays a role in cell adhesion and tumor progression, but its function in fibrogenesis has not been explored. In this in vitro study, we found that GPR56 in IPF fibroblasts was lower than in normal fibroblasts. GPR56 regulated the production of fibronectin and type I collagen, and also changed the migratory and invasive capacity of lung fibroblasts. However, it was not sufficient to activate some classic markers of fibroblast and myofibroblast, such as α-smooth muscle actin and fibroblast specific protein 1. These findings demonstrate that reduced expression of GPR56 in lung fibroblasts may be an important link with pulmonary fibrosis, playing a role in regulating some important fibroblast functions.

[Meta-analysis of oral squamous cell carcinoma on gene expression level].

OBJECTIVE: To study the differently expressed genes of oral squamous cell carcinoma (OSCC) tissue. METHODS: Gene expression datasets related to oral squamous cell carcinoma in the gene expression omnibus (gene expression omnibus, GEO) repository were retrieved. Datasets were merged by normalization.Significantly expressed genes were obtained by statistical methods, and genes' functions, interactions, signaling pathways were analyzed accordingly. RESULTS: In GEO, there were 1 125 records related to OSCC, and four of them were selected and merged to a super array data, within the super array data, 233 genes were significantly expressed (P < 0.05) , and the top 100 significantly expressed genes were selected as signature genes.Signature genes were more related to cell surface or cell-cell interactive activities. Clusters of interactive signature genes and the related signaling pathways were related with mitosis process. CONCLUSIONS: OSCC signature genes and the corresponding signaling pathways will provide not only an important clue for further research of the disease, but also reference for diagnosis and treatment.

Meta-analysis of genetic programs between idiopathic pulmonary fibrosis and sarcoidosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) and pulmonary sarcoidosis are typical interstitial lung diseases with unknown etiology that cause lethal lung damages. There are notable differences between these two pulmonary disorders, although they do share some similarities. Gene expression profiles have been reported independently, but differences on the transcriptional level between these two entities have not been investigated. METHODS/RESULTS: All expression data of lung tissue samples for IPF and sarcoidosis were from published datasets in the Gene Expression Omnibus (GEO) repository. After cross platform normalization, the merged sample data were grouped together and were subjected to statistical analysis for finding discriminate genes. Gene enrichments with their corresponding functions were analyzed by the online analysis engine "Database for Annotation, Visualization and Integrated Discovery" (DAVID) 6.7, and genes interactions and functional networks were further analyzed by STRING 9.0 and Cytoscape 3.0.0 Beta1. One hundred and thirty signature genes could potentially differentiate one disease state from another. Compared with normal lung tissue, tissue affected by IPF and sarcoidosis displayed similar signatures that concentrated on proliferation and differentiation. Distinctly expressed genes that could distinguish IPF from sarcoidosis are more enriched in processes of cilium biogenesis or degradation and regulating T cell activations. Key discriminative network modules involve aspects of bone morphogenetic protein receptor two (BMPR2) related and v-myb myeloblastosis viral oncogene (MYB) related proliferation. CONCLUSIONS: This study is the first attempt to examine the transcriptional regulation of IPF and sarcoidosis across different studies based on different working platforms. Groups of significant genes were found to clearly distinguish one condition from the other. While IPF and sarcoidosis share notable similarities in cell proliferation, differentiation and migration, remarkable differences between the diseases were found at the transcription level, suggesting that the two diseases are regulated by overlapping yet distinctive transcriptional networks.

[Burkitt's lymphoma of the spermatic cord: a case report and review of the literature].

OBJECTIVE: To investigate the clinicopathological characteristics of primary Burkitt's lymphoma (BL) in the spermatic cord. METHODS: A case of BL of the spermatic cord was studied by histopathology and immunohistochemical techniques. The clinical data and the related literature were reviewed. RESULTS: The patient was a 4-year-old boy, who was accidentally found with a bump in the scrotum. Surgery showed it to be a tumor located in the left spermatic cord and 5 cm x 3 cm x 2 cm in size, gray and fish-like on cross-sectional imaging. Histologically, it was characterized by monotonous infiltration of medium-sized cells with round nuclei, coarse chromatin, 2-5 basophilic nucleoli, and an appreciable rim of basophilic cytoplasm, in a typically starry-sky pattern imparted by interspersed tangible-body macrophages. Immunohistochemically, the tumor cells were diffused, positive for CD20 and CD79, some for CD10 and about 95% with the nuclear expression of Ki-67, but negative for CD3, CD43, bcl-2 and TdT as well as for EBER in situ hybridization. CONCLUSION: Primary spermatic cord BL is extremely rare, highly aggressive and with poor prognosis. Diagnosis of the tumor relies on its pathological characteristics and immunohistochemical staining. It is essential to differentiate BL from other types of lymphomas and malignant small-cell tumors of the non-lymphatic system.