Gene expression profiling of ovarian carcinomas and prognostic analysis of outcome.

BACKGROUND: Ovarian cancer (OCA), the fifth leading deaths cancer to women, is famous for its low survival rate in epithelial ovarian cancer cases, which is very complicated and hard to be diagnosed from asymptomatic nature in the early stage. Thus, it is urgent to develop an effective genetic prognostic strategy. METHODS: Current study using the Database for Annotation, Visualization and Integrated Discovery tool for the generation and analysis of quantitative gene expression profiles; all the annotated gene and biochemical pathway membership realized according to shared categorical data from Pathway and Kyoto Encyclopedia of Genes and Genomes; correlation networks based on current gene screening actualize by Weighted correlation network analysis to identify therapeutic targets gene and candidate bio-markers. RESULTS: 3095 differentially expressed genes were collected from genome expression profiles of OCA patients (n = 53, 35 advanced, 8 early and 10 normal). By pathway enrichment, most genes showed contribution to cell cycle and chromosome maintenance.1073 differentially expression genes involved in the 4 dominant network modules are further generated for prognostic pattern establish, we divided a dataset with random OCA cases (n = 80) into 3 groups efficiently (p = 0.0323, 95% CIs in Kaplan-Meier). Finally, 6 prognosis related genes were selected out by COX regression analysis, TFCP2L1 related to cancer-stem cell, probably contributes to chemotherapy efficiency. CONCLUSIONS: Our study presents an integrated original model of the differentially expression genes related to ovarian cancer progressing, providing the identification of genes relevant for its pathological physiology which can potentially be new clinical markers.

Elevated SHOX2 expression is associated with tumor recurrence of hepatocellular carcinoma.

BACKGROUND: SHOX2 (short stature homeobox 2) is a crucial transcriptional regulator in several genetic disorders and has been demonstrated to be an excellent biomarker in the diagnosis and evaluation of lung cancer. However, its expression pattern and prognostic value for hepatocellular carcinoma (HCC) are still unknown. METHODS: Expression of SHOX2 gene and protein in HCC tissues and cell lines were evaluated by RT-qPCR and western blot. Impact of RNAi-mediated SHOX2 silence on the proliferation and invasion ability of Huh7 cell line in vitro was determined by CCK-8 assay and matrigel invasion assay, respectively. RESULTS: Elevated expression of SHOX2 gene was significantly associated with higher incidence of tumor recurrence (n = 60, p = 0.001), absence of tumor capsule (p = 0.015), presence of tumor thrombi (p < 0.0001), and advanced TNM stage (p < 0.0001) of HCC. SHOX2 protein expression was more abundant in HCC cell lines compared with hepatic cell line (p = 0.001), which was associated with tumor recurrence (n = 40, p = 0.046). RNAi-mediated silence of SHOX2 expression significantly inhibited the proliferation (p < 0.001) and invasion (p = 0.006) of Huh7 cell line in vitro. CONCLUSIONS: Elevated SHOX2 expression was associated with HCC recurrence, probably by enhancing proliferation and invasion capability of cancer cells.

Krüppel-like factor 8 is a new Wnt/beta-catenin signaling target gene and regulator in hepatocellular carcinoma.

Krüppel-like factor 8 (KLF8) plays important role in cell cycle and oncogenic transformation. Here we report the mechanisms by which KLF8 crosstalks with Wnt/ß-catenin signaling pathway and regulates hepatocellular carcinoma (HCC) cells proliferation. We show that overexpression of KLF8 and nucleus accumulation of ß-catenin in the human HCC samples are positively correlated. More importantly, KLF8 protein levels plus nucleus accumulation of ß-catenin levels were significantly elevated in high-grade HCC compared to low-grade HCC. Using HCC HepG2 cells we find that, on the one hand both protein and mRNA of KLF8 are up-regulated under Wnt3a stimulation, on the other hand overexpression of KLF8 increases the cytoplasm and nucleus accumulation of ß-catenin, recruits p300 to ß-catenin/T-cell factor 4 (TCF4) transcription complex, enhances TOP flash report gene transcription, and induces Wnt/ß-catenin signaling target genes c-Myc, cyclin D1 and Axin1 expression. Knockdown of KLF8 using shRNA inhibits Wnt3a induced transcription of TOP flash report gene and expression of c-Myc, cyclin D1 and Axin1. Knockdown of ß-catenin by shRNA rescues the enhanced HepG2 and Hep3B cells proliferation ability induced by overexpression of KLF8.