Multi-omics Analyses Reveal Function of Apolipoprotein E in Alternative Splicing and Tumor Immune Microenvironment in Kidney Renal Clear Cell Carcinoma via Pan-cancer Analysis.

Apolipoprotein E (APOE) regulates lipid metabolism, associated with the development of various cancers. However, its precise prognostic significance and functions in alternative splicing and the tumor immune microenvironment remain unclear. In this study, we extracted APOE expression in pan-cancer from TCGA and analyzed mRNA transcriptome, cell lines, and protein levels. Furthermore, we analyzed the alternative splicing expression of the APOE gene transcript with prognostic profiles using the OncoSplicing database. We obtained 73 common APOE genes to perform functional enrichment analysis, assess the correlation between genes and immune cells using TIMER, EPIC, and ssGSEA methods, and examine the prognostic significance using the UALCAN database. Finally, single-cell data was employed to assess the correlation between APOE genes and cell functions. Our findings revealed that APOE expression varies across different tumor types and cancer cell lines. The alternative splicing analysis demonstrated that APOE transcript expression levels have prognostic value in cancers such as LGG, KIRC, and KIRP. Functional enrichment analysis indicated significant associations between APOE and various immune cells, such as macrophages, CD8 T cells, and NK cells, with significant implications for prognosis. Moreover, single-cell data indicated that APOE was primarily expressed in renal epithelial cells among stromal cells and in macrophages among immune cells, significantly negatively correlated with five functional states. Our study represents the first comprehensive exploration of APOE's function in pan-cancers and identifies APOE as a potential biomarker in cancer pathogenesis, prognosis, and immune therapeutic target.

Berberine targets epidermal growth factor receptor signaling to suppress prostate cancer proliferation in vitro.

Berberine is a well­known component of the Chinese herbal medicine Huanglian (Coptis chinensis), and is capable of inhibiting the proliferation of multiple cancer cell lines. However, information available regarding the effect of berberine on prostate cancer cell growth is limited. In the present study, LnCaP and PC­3 human prostate cancer cell lines were selected as in vitro models in order to assess the efficacy of berberine as an anticancer agent. A cell proliferation assay demonstrated that berberine inhibited cell growth in a dose­and time­dependent manner. Further investigation revealed berberine significantly accumulated inside cells that were in the G1 phase of the cell cycle and enhanced apoptosis. Western blot analysis demonstrated that berberine inhibited the expression of prostate­specific antigen and the activation of epidermal growth factor receptor (EGFR), and it attenuated EGFR activation following EGF treatment in vitro. In conclusion, the results indicate that berberine inhibits the proliferation of prostate cancer cells through apoptosis and/or cell cycle arrest by inactivation of the EGFR signaling pathway.

Diagnostic value of endobronchial ultrasound guided transbronchial needle aspiration in superior vena cava syndrome.

BACKGROUND: The pathological diagnosis is of critical importance to the subsequent treatment for the pathients with superior vena cava syndrome (SVCS). The aim of this study is to report our experience in the diagnosis of SVCS by endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA). METHODS: The data of 520 patients who underwent EBUS-TBNA from September 2009 to May 2012 at our institution were reviewed. Of these, there were 14 males and 6 females (mean age of 59.1 years) with SVCS who received EBUS-TBNA that were included in the analysis. RESULTS: The mean short axis diameter of the paratracheal lesions was (3.32 ± 1.79) cm (range, 1.69 to 9.50 cm) and 6 cases also had subcarinal lymph node enlargement with a mean short axis diameter of (2.14 ± 0.49) cm (range, 1.73 to 3.01 cm). An average of 4.3 punctures was performed per lesion. Malignancy was confirmed in 16 cases (10 small cell carcinomas, 4 adenocarcinomas, 1 squamous cell carcinoma and 1 Hodgkin lymphoma). In two patients, pathological examination of tissue revealed no evidence of malignancy and for 13 to 24 months of follow-up. One patient from whom adequate tissue was not obtained refused further surgical biopsy since he had undergone endovascular stenting of the SVC. One patient in whom a diagnosis was not obtained by EBUS-TBNA underwent thoracoscopic biopsy and the final diagnosis was B cell non-Hodgkin's lymphoma. The diagnosis accuracy of EBUS-TBNA in SVCS was 18/20 patients. CONCLUSION: EBUS-TBNA is a highly effective and safe procedure for the diagnosis of SVCS.

[Gastrointestinal mesenchymal tumors: a clinical pathologic and immunohistochemical study of 210 cases].

OBJECTIVE: To study the clinical pathologic and immunohistochemical features of gastrointestinal mesenchymal tumors (GIMTs), and to investigate the value of molecular markers in GIMTs clinical differentiation diagnosis. METHODS: The clinical and pathological data of 210 cases of GIMTs, collected from Jan. 1987 to Dec. 2005 in our hospital, were investigated retrospectively. GIMTs were rediagnosed by using standard immunostaining technique in paraffin-embedded tissue. The expression level of CD117, CD34, Desmin, SMA and PS100 were detected by immunohistochemical method. RESULTS: Among 210 cases of GIMTs, 127 cases were Gastrointestinal stromal tumors (GISTs) (60.5%), 33 leiomyomas and leiomyosarcomas (15.7%), 27 neurogenic tumours (12.8%), and 23 miscellaneous tumors (11.0%). The incidences of GIST, leiomyoma and leiomyosarcoma were similar among men and women. Men were more likely to develop neurogenic tumors and miscellaneous tumors than women. Of all the GISTs, 51.2% cases originated from stomach, 19.7% from small intestine, 11.0% from esophagus, 10.2% from colon and rectum. The most common location of leiomyomas and leiomyosarcomas was esophagus (45.5%). The most common location of neurogenic tumors was retroperitoneum (74.1%). Common symptoms of GISTs included digestive tract hemorrhage in 36 cases (28.3%), abdominal pain in 27 cases (21.3%) and abdominal mass in 24 cases (18.9%). Other GIMT cases except GISTs had no first symptom of digestive tract hemorrhage. It was noticed that 79.5% of GISTs had no obvious invasion, and 72.7% of leiomyomas and leiomyosarcomas had no obvious invasion. 33.3% of neurogenic tumors invaded the adjacent organs or tissues. No metastases had been found in other GIMT cases except GISTs. The neoplastic cells of GISTs were composed of various percentage of spindle (72.5%), epithelioid (11.8%) and mixed-type cells (15.7%). The percentage of spindle cells in leiomyomas and leiomyosarcomas was 94. The immunohistochemical results of GISTs showed that the positive rate of CD117 was 93.7%, CD34 was 69.3%, Desmin was 13.4%, SMA was 12.6%, and PS100 was 10.2%. The immunohistochemical results of leiomyomas and leiomyosarcomas showed that the positive rate of Desmin was 78.5%, SMA was 63.6%, while as the expressions of CD117, CD34, and PS100 were negative. Diffuse strong positive staining of PS100 was observed in 88.9% of neurogenic tumor patients. CONCLUSIONS: GISTs are the most common tumors among GIMTs. GISTs are different from neurogenic tumors, leiomyomas and leiomyosarcomas in initial symptom, tumor location, biological behavior and immunophenotype. Immunohistochemistry plays an important role in differentiating GISTs from leiomyomas and neurogenic tumors.