Gene expression profile association with poor prognosis in epithelial ovarian cancer patients.
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ABSTRACT:
SUBMITTER: Oliveira DVNP
PROVIDER: S-EPMC7940404 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:ATP-binding cassette (ABC) transporters play various roles in cancer biology and drug resistance, but their association with outcomes in serous epithelial ovarian cancer (EOC) is unknown. METHODS:The relationship between clinical outcomes and ABC transporter gene expression in two independent cohorts of high-grade serous EOC tumors was assessed with real-time quantitative polymerase chain reaction, analysis of expression microarray data, and immunohistochemistry. Associations between clinical outcomes and ABCA transporter gene single nucleotide polymorphisms were tested in a genome-wide association study. Impact of short interfering RNA-mediated gene suppression was determined by colony forming and migration assays. Association with survival was assessed with Kaplan-Meier analysis and log-rank tests. All statistical tests were two-sided. RESULTS:Associations with outcome were observed with ABC transporters of the "A" subfamily, but not with multidrug transporters. High-level expression of ABCA1, ABCA6, ABCA8, and ABCA9 in primary tumors was statistically significantly associated with reduced survival in serous ovarian cancer patients. Low levels of ABCA5 and the C-allele of rs536009 were associated with shorter overall survival (hazard ratio for death = 1.50; 95% confidence interval [CI] =1.26 to 1.79; P = 6.5e-6). The combined expression pattern of ABCA1, ABCA5, and either ABCA8 or ABCA9 was associated with particularly poor outcome (mean overall survival in group with adverse ABCA1, ABCA5 and ABCA9 gene expression = 33.2 months, 95% CI = 26.4 to 40.1; vs 55.3 months in the group with favorable ABCA gene expression, 95% CI = 49.8 to 60.8; P = .001), independently of tumor stage or surgical debulking status. Suppression of cholesterol transporter ABCA1 inhibited ovarian cancer cell growth and migration in vitro, and statin treatment reduced ovarian cancer cell migration. CONCLUSIONS:Expression of ABCA transporters was associated with poor outcome in serous ovarian cancer, implicating lipid trafficking as a potentially important process in EOC.
| S-EPMC4110473 | biostudies-literature
Project description:Epithelial ovarian cancer (EOC) is one of the deadly gynecological malignancies. The function of protein kinase CK2? (CK2?) in EOC is still unknown. Our study aimed to investigate the relationship between the protein expression of CK2? and the tumor progression, the prognosis of human EOC. In this study, we analyzed the expression levels of CK2? through Western blot, using EOC cell lines like A2780, HO8910, COV644, OVCAR3, SKOV3, and the primary normal ovarian surface epithelial (NOSE) cells. Furthermore, OVCAR3 and SKOV3 EOC cells were employed as a cellular model to study the role of CK2? on cell growth, migration, invasion, apoptosis, and cell cycle distribution. In addition, we investigated CK2? protein expression in tumor tissues from patients with EOC by immunohistochemistry and analyzed the association between CK2? expression and clinicopathologic parameters and prognosis of EOC patients. And we found that compared with NOSE cells, CK2? protein expression was increased in A2780, HO8910, OVCAR3, and SKOV3 ovarian cancer cell lines. Decreased CK2? expression suppressed OVCAR3 and SKOV3 cell growth and induced more apoptosis. CK2? knockdown using specific siRNAs inhibited migration and invasion ability of OVCAR3 and SKOV3 cells. In addition, high CK2? protein expression was found in 68.4% (80/117) of EOC patients. Increased CK2? expression of was significantly correlated with FIGO staging and peritoneal cytology. Patients with higher CK2? expression had a significantly poorer overall survival compared with those with lower CK2? expression. Multi-variate Cox regression analysis proved that increased CK2? expression was an independent prognostic marker for EOC. Taken together, our data displayed that CK2? may play a role in tumor aggressive behavior of EOC and could be used as a marker for predicting prognosis of EOC patient. High CK2? expression might predict poor patient survival.
| S-EPMC5371331 | biostudies-literature
Project description:Tumor microenvironment plays an important role in regulating cell growth and metastasis. Recently we developed an ex vivo lung cancer model (4D) that forms perfusable tumor nodules on a lung matrix that mimics human lung cancer histopathology and protease secretion pattern. We compared the gene expression profile (Human OneArray v5 chip) of A549 cells, a human lung cancer cell line, grown on petri dish (2D), and of the same cells grown in the matrix of our ex vivo model (4D). Furthermore, we obtained gene expression data of A549 cells grown on petri dish (2D) and matrigel (3D) from a previous study and compared the 3D expression profile with that of 4D. Expression array analysis showed 2954 genes differentially expressed between 2D and 4D. Gene Ontology (GO) analysis showed up-regulation of several genes associated with extracellular matrix, polarity, and cell fate and development. Moreover, expression array analysis of 2D versus 3D showed 269 genes that were most differentially expressed, with only 35 genes (13%) having similar expression patterns as observed between 2D and 4D. Finally, the differential gene expression signature of 4D cells (versus 2D) correlated significantly with poor survival in patients with lung cancer (n=1492), while the expression signature of 3D versus 2D correlated with better survival in lung cancer patients. Since patients with larger tumors tend to have worse survival, the ex vivo 4D model may offer additional features over the 3D model, to better mimic of natural progression of tumor growth in lung cancer patients. We compared the gene expression profile (Human OneArray v5 chip) of A549 cells, human lung cancer cell line, grown on petri dish (2D) and same cells grown in the matrix of our ex vivo model (4D).
| S-ECPF-GEOD-45142 | biostudies-other
Project description:BACKGROUND:Low expression of NCALD(neurocalcin delta) in peripheral blood of ovarian cancer patients predicts poor prognosis. However, the molecular mechanism of NCALD in ovarian cancer and its relationship with chemotherapy outcomes is unclear. The aim of this study was to investigate the potential signaling pathways of NCALD and to evaluate its ability to predict chemotherapy outcomes and prognosis. METHODS:High-throughput RNA sequencing data were downloaded from TCGA. GSEA explored the potential signaling pathways of NCALD. The expression of NCALD in chemotherapy sensitive and chemotherapy resistant ovarian cancer patients was detected by TCGA data and clinical samples. ROC analysis confirmed the ability of NCALD to predict chemotherapy outcomes. The association between NCALD expression and prognosis in ovarian cancer patients was assessed using Kaplan-Meier plotter. RESULTS:In patients with NCALD overexpression, genes expression related to ERK1 / 2 signaling pathway, NF-kappaB signaling pathway, TGF-? signaling pathway and immune response pathway was increased, especially ERK1 / 2 signaling pathway. The expression of NCALD in chemoresistant patients was significantly lower than chemosensitive patients. In TCGA data and immunohistochemical samples, the AUC of NCALD expression predicting chemotherapy outcome was 0.59 and 0.64, respectively. In clinical samples, low expression of NCALD was associated with poor OS and PFS. CONCLUSIONS:NCALD may activate the ERK1 / 2 signaling pathway in ovarian cancer. As a new biomarker of chemotherapy sensitivity, NCALD was significantly down-regulated in chemotherapy resistance ovarian cancer patients. Low expression of NCALD in ovarian cancer is associated with poor OS and PFS. In the future, further research will be needed on the potential mechanism and clinical application value of NCALD in ovarian cancer.
| S-EPMC7106630 | biostudies-literature
Project description:The tumor microenvironment plays an important role in regulating cell growth and metastasis. Recently, we developed an ex vivo lung cancer model (four dimensional, 4D) that forms perfusable tumor nodules on a lung matrix that mimics human lung cancer histopathology and protease secretion pattern. We compared the gene expression profile (Human OneArray v5 chip) of A549 cells, a human lung cancer cell line, grown in a petri dish (two-dimensional, 2D), and of the same cells grown in the matrix of our ex vivo model (4D). Furthermore, we obtained gene expression data of A549 cells grown in a petri dish (2D) and matrigel (three-dimensional, 3D) from a previous study and compared the 3D expression profile with that of 4D. Expression array analysis showed 2,954 genes differentially expressed between 2D and 4D. Gene ontology (GO) analysis showed upregulation of several genes associated with extracellular matrix, polarity and cell fate and development. Moreover, expression array analysis of 2D vs. 3D showed 1,006 genes that were most differentially expressed, with only 36 genes (4%) having similar expression patterns as observed between 2D and 4D. Finally, the differential gene expression signature of 4D cells (vs. 2D) correlated significantly with poor survival in patients with lung cancer (n = 1,492), while the expression signature of 3D vs. 2D correlated with better survival in lung cancer patients with lung cancer. As patients with larger tumors have a worse rate of survival, the ex vivo 4D model may be a good mimic of natural progression of tumor growth in lung cancer patients.
| S-EPMC4070715 | biostudies-literature
Project description:The cancer testis antigen, melanoma-associated antigen A9 (MAGE-A9), is expressed in many kinds of different human cancers, and is an important target for immunotherapy. However, the clinicopathologic significance of MAGE-A9 in epithelial ovarian cancer (EOC) is unknown. In this study, real-time PCR (12 carcinomas of high FIGO stage, 12 carcinomas of low FIGO stage, and 20 normal ovary or fallopian tube tissues) and immunohistochemistry by tissue microarrays (128 carcinomas and 112 normal ovary or fallopian tube tissues, benign or borderline ovarian tumor tissues) were performed to characterize expression of MAGE-A9 in EOC. We found that significantly higher MAGE-A9 mRNA expression in EOC tumors than that in normal ovary or fallopian tube tissues (all P < 0.05). Protein expression of MAGE-A9 was significantly associated with FIGO stage, high histological grade, level of CA-125 and metastasis. Consistent with the associated poor clinicopathologic features, patients with MAGE-A9(H (high-expressing)) tumors had a worse overall survival as compared to patients with MAGE-A9(L (low or none-expressing)) tumors. Further studies revealed that MAGE-A9 overexpression was an independent prognostic factor for overall survival (OS). Multivariate analysis showed that patients with MAGE-A9 overexpressing tumors had extremely poor OS. These findings indicate that MAGE-A9 expression may be helpful in predicting EOC prognosis.
| S-EPMC4502509 | biostudies-other
Project description:Collagen triple helix repeat-containing 1 (CTHRC1) is aberrantly overexpressed in multiple malignant tumors. However, the expression characteristics and function of CTHRC1 in epithelial ovarian cancer (EOC) remain unclear. We found that CTHRC1 expression was up-regulated in the paraffin-embedded EOC tissues compared to borderline or benign tumor tissues. CTHRC1 expression was positively correlated with tumor size (p = 0.008), menopause (p = 0.037), clinical stage (p = 0.002) and lymph node metastasis (p < 0.001) and was also an important prognostic factor for the overall survival of EOC patients, as revealed by Kaplan-Meier analysis. CTHRC1 increased the invasive capabilities of EOC cells in vitro by activating the Wnt/β-catenin signaling pathway. We showed that ectopic transfection of CTHRC1 in EOC cells up-regulated the expression of EMT markers such as N-cadherin and vimentin, and EMT-associated transcriptional factor Snail. Knockdown of CTHRC1 expression in EOC cells resulted in down-regulation of N-cadherin, vimentin, Snail and translocation of β-catenin. Collectively, CTHRC1 may promote EOC metastasis through the induction of EMT process and serve as a potential biomarker for prognosis as well as a target for therapy.
| S-EPMC4742143 | biostudies-literature
Project description:Epithelial ovarian carcinomas (EOC) cause more mortality than any other cancer of the female reproductive system. New therapeutic approaches to reduce EOC mortality have been largely unsuccessful due to the poor understanding of the mechanisms underlying EOC proliferation and metastasis. Progress in EOC treatment is further hampered by a lack of reliable prognostic biomarkers for early risk assessment. In this study, we identify that Migration-Inducting Gene 7 (MIG-7) is specifically induced in human EOC tissues but not normal ovaries or ovarian cyst. Ovarian MIG-7 expression strongly correlated with EOC progression. Elevated MIG-7 level at the time of primary cytoreductive surgery was a strong and independent predictor of poor survival of EOC patients. Cell and murine xenograft models showed that MIG-7 was required for EOC proliferation and invasion, and MIG-7 enhanced EOC-associated angiogenesis by promoting the expression of vascular endothelial growth factor. Inhibiting MIG-7 by RNA interference in grafted EOC cells retarded tumor growth, angiogenesis and improved host survival, and suppressing MIG-7 expression with a small molecule inhibitor D-39 identified from the medicinal plant Liriope muscari mitigated EOC growth and invasion and specifically abrogated the expression of vascular endothelial growth factor. Our data not only reveal a critical function of MIG-7 in EOC growth and metastasis and support MIG-7 as an independent prognostic biomarker for EOC, but also demonstrate that therapeutic targeting of MIG-7 is likely beneficial in the treatment of EOC.
| S-EPMC5053671 | biostudies-literature
Project description:Stress-induced phosphoprotein1 (STIP1) is a candidate biomarker in epithelial ovarian cancer (EOC). In this study, we investigated in detail the expression of STIP1, as well as its functions, in EOC. STIP1 expression was assessed by immunohistochemistry (IHC) and the results were compared with clinicopathologic factors, including survival data. The effects of STIP1 gene silencing via small interfering RNA (siRNA) were examined in EOC cells and a xenograft model. The expression of STIP1 protein in EOC was significantly higher than in the other study groups (P?<?0.001), and this increase of expression was significantly associated with tumor stage (P?=?0.005), tumor grade (P?=?0.029), and lymph node metastasis (P?=?0.020). In multivariate analysis, overall survival in EOC was significantly shorter in cases with high STIP1 expression (HR?=?2.78 [1.01-7.63], P?=?0.047). STIP1 silencing in EOC cells resulted in inhibition of cell proliferation and invasion. In addition, in vivo experiments using STIP1 siRNA clearly showed a strong inhibition of tumor growth and a modulation of expression of prosurvival and apoptotic genes, further suggesting that STIP1 silencing can prevent cell proliferation and invasion. In conclusion, increased STIP1 expression is associated with poor survival outcome in EOC, and STIP1 may represent a useful therapeutic target in EOC patients.
| S-EPMC7665810 | biostudies-literature
Project description:Circulating microRNAs have recently emerged as a new class of promising non-invasive cancer biomarkers. The purpose of this study was the identification by a high-throughput approach (miRNA microarray) of circulating miRNAs associated with breast cancer-derived distant metastasis. To achieve this goal, we resorted to archival plasma samples collected from patients in the control arm of a randomized clinical trial on stage I breast cancer. We compared plasma miRNA levels in patients that developed distant metastasis after a radical or conservative surgery and in those long-term disease-free. Microarray results were technically and independently validated by Real Time PCR. Subsequent in vitro, in vivo and in silico analyses were performed to investigate the miRNA biological/clinical significance in relation with breast cancer progression. We demonstrated that high circulating miR-1246 levels were associated to distant metastasis and that high tissue expression of this miRNA was correlated with unfavorable outcome in ER+HER2- breast cancer patients. In addition, miR-1246 expression was also found to be related with stem-like features. 64 samples (32 patients with metastasis and 32 patients with no metastasis) were considered from a total of 208 hybridized samples collected between 1987 and 2004 (including 94 paired samples according to tumor ER status, age at drawing, drawing year, time from surgery, 7 additional samples from 'no evidence of disease' (NED) patients, 10 references, 1 healthy donor and 2 replicated samples)
2015-08-31 | E-GEOD-68373 | biostudies-arrayexpress