Gene expression profiling of paired ovarian tumors obtained prior to and following adjuvant chemotherapy: Molecular signatures of chemoresistant tumors

L’Espérance, Sylvain; Popa, Ion; Bachvarova, Magdalena; Plante, Marie; Patten, Nancy; Wu, Lin; Têtu, Bernard; Bachvarov, Dimcho

doi:10.3892/ijo.29.1.5

Cited by 88 publications

(115 citation statements)

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“…13 A serious constraint was their commercial availability. The antibodies are presented in the Table 1.…”

Section: Methodsmentioning

confidence: 99%

“…11 We recently analyzed the gene expression patterns in advanced (FIGO stages III and IV) primary serous papillary carcinomas of the ovary displaying different response to first line chemotherapy in an attempt to identify specific molecular signatures associated with clinical response to chemotherapy. 12,13 Initially, the expression profiles of 15 chemoresistant serous papillary carcinomas (recurrence r6 months) and 10 chemosensitive serous papillary carcinomas (recurrence Z30 months) tumors were independently analyzed which allowed the identification of 155 genes with different expression in the chemoresistant or the chemosensitive phenotype. The 155 genes differently expressed at a P-value cutoff of 0.01 were upregulated or downregulated at least 2-fold in chemoresistant tumors in comparison with chemosensitive tumors.…”

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confidence: 99%

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Immunohistochemical analysis of possible chemoresistance markers identified by micro-arrays on serous ovarian carcinomas

et al. 2008

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Using the DNA microarray technology, we have identified genes that are differentially expressed in chemosensitive and chemoresistant ovarian serous papillary carcinomas and could potentially distinguish ovarian cancer patients based on their response to chemotherapy. The present study aims to evaluate the clinical usefulness of overexpression of selected genes by immunohistochemistry. Our cohort included 158 women who were operated on and received chemotherapy for an advanced serous papillary ovarian carcinoma (FIGO stages III and IV). The end point used in this study was progression-free survival. Immunohistochemistry was performed on microarray blocks containing all 158 cases. Twelve commercially available antibodies were selected. Of them, 10 corresponded to differentially expressed genes in our micro-array study and p53 and Ki67 were included. Antibodies were obtained for the following selected genes: GSTA1, MMP1, FOSB, CTSL2, HSP10, CD36, CXCL2, RBBP7, Siva, and PTGDS. Cox proportional hazards models, adjusted for standard risk factors, were used to estimate the associations between the markers and progression-free survival. No association was found between mRNA level and protein expression by immunohistochemistry. In multivariate analyses, patients whose tumors overexpressed HSP10 had a lower risk of progression than those with low expression (HR: 0.6; CI: 0.42-0.87; P ¼ 0.007). High level of proliferation (Ki67) tended to be associated with a lower risk of progression (HR: 0.72; CI: 0.51-1.03; P ¼ 0.07) whereas MMP1 overexpression tended to be associated with a higher risk of progression (HR: 1.61; CI: 0.94-2.79; P ¼ 0.08). Our study shows that gene expression analysis coupled with immunohistochemistry allowed the identification of HSP10 as an independent factor of progression-free survival. Modern Pathology (2008Pathology ( ) 21, 1002Pathology ( -1010 doi:10.1038/modpathol.2008 published online 23 May 2008 Keywords: serous ovarian carcinoma; chemoresistance; HSP10; DNA microarray; immunohistochemistry Ovarian cancer is responsible for more cancer deaths among women in the Western world than any other gynecologic malignancy. 1 An initial surgical approach is essential for aggressive cytoreduction and proper staging of the disease, since minimal residual tumor after surgery is a major factor of better response to chemotherapy and survival. 2 Intravenous combinated chemotherapy with taxol plus carboplatin is the current regimen of choice for the treatment of advanced ovarian cancer and is followed by a 50% complete pathologic remission rate. 3 Resistance to chemotherapy is, however, a major concern. Indeed, although significant proportions of women respond to chemotherapy, the majority of responders (approximately 60-75%) eventually relapses and dies from recurrent disease while 20-30% of patients never experience a clinical remission. 4 Chemotherapy resistance in ovarian

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“…13 A serious constraint was their commercial availability. The antibodies are presented in the Table 1.…”

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Immunohistochemical analysis of possible chemoresistance markers identified by micro-arrays on serous ovarian carcinomas

et al. 2008

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“…COX-1 and COX-2 have been reported to be the potential target for the treatment of epithelial ovarian cancer. [31][32][33] Peroxisome proliferator-activated receptor gamma, which is known to negatively regulate COX-2 (a prostaglandin synthetase), can be a potential therapeutic target, especially in recurrent tumors. 34 In the current study, COX-2 overexpression was found to be the only independent molecular prognostic factor in type II tumors among the 5 inflammatory molecules investigated.…”

Section: Recently Kurman Et Al Proposed a New Classification Ofmentioning

confidence: 99%

Molecular typing of epithelial ovarian carcinomas using inflammatory markers

Ali-Fehmi

Semaan

Sethi

et al. 2010

Cancer

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BACKGROUND: Ovarian epithelial carcinomas have recently been classified as slow growing type I tumors and rapidly growing highly aggressive type II tumors. The present study sought to molecularly characterize type I and II tumors using known molecular markers. METHODS: Specimens from 213 patients with ovarian carcinoma were categorized as type I or type II, and evaluated by immunohistochemistry for the inflammatory markers glucose transporter protein-1 (Glut-1), inducible nitric oxide synthase (iNOS), cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), and nuclear factor kappa B. Statistical analysis was performed to investigate whether these molecular markers could distinguish between type I and type II tumors. Kaplan-Meier survival curves and COX regression analysis were used to determine the prognostic effect of these markers on survival in the 2 types of tumors. RESULTS: Overexpression of COX-1, COX-2, iNOS, and Glut-1 was significantly higher in type II tumors (P < .05). Women with type II tumors had a poorer median survival (60 months) as compared with those with type I tumors (141 months) (P ¼.0001). Multivariate analysis revealed type II tumors, late stage, and age >60 years as significant predictors of poor survival. For type II tumors, median survival of patients with tumors overexpressing COX-2 was 44 compared with 85 months for those with tumors with low COX-2 expression (P ¼.029). Looking at both type I and II tumors, the number of markers simultaneously overexpressed in each tumor was a significant predictor of poor patient survival (P ¼.005). CONCLUSIONS: The present study demonstrates that the new proposed histologic classification of ovarian epithelial carcinomas correlates with a distinct expression of inflammatory pathway proteins. High expression of these markers may explain the different biologic behavior of these 2 tumor types and provide targets for therapy. Cancer 2011;117:301-9.

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“…AXIN1 serves as a scaffold protein through interacting with numerous proteins, enabling it to facilitate the degradation β-catenin, which suggests that it has a tumor suppressor function (22). Several signaling pathways, including that of Wnt, TGF-β, JNK1 and p53, have been reported to be associated with AXIN1 (23)(24)(25). A previous study suggested that AXIN1 mutation may be associated with germ cell tumors (17).…”

Section: Discussionmentioning

confidence: 99%

AXIN1 protects against testicular germ cell tumors via the PI3K/AKT/mTOR signaling pathway

Yan

Jia

et al. 2017

Oncology Letters

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Abstract. Axis inhibition protein 1 (AXIN1) is characterized as a tumor suppressor in numerous types of cancer. However, the functional role of AXIN1 in the testicular germ cell tumors (TGCTs) remains unclear. The human embryonal carcinoma-derived cell line NTera2 was transfected with a recombinant AXIN1 expression vector (pcDNA3.1-AXIN1) and/or a small interfering RNA (siRNA) directed against AXIN1 (siAXIN). Following transfection, the mRNA and protein levels of AXIN1 were determined via reverse transcription-quantitative polymerase chain reaction analysis and western blotting, respectively. In addition, cell viability, apoptosis and the expression of apoptosis-associated proteins [apoptosis regulator Bax (Bax) and B-cell lymphoma (Bcl)-2] and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway proteins [phosphorylated (p)-mTOR, mTOR, p-AKT, AKT, P-70S ribosomal protein S6 (S6) and S6] were assessed. AXIN1 mRNA and protein levels were increased following transfection with pcDNA3.1-AXIN1 and decreased following transfection with siAXIN1 compared with their respective control groups. After overexpression of AXIN1, NTera2 cell viability and expression of Bcl-2, p-mTOR p-AKT and p-S6 protein was decreased, while apoptosis and Bax protein levels were increased, compared with the control group. However, there was no significant difference in AXIN1 mRNA expression, apoptosis or Bax/Bcl-2 protein expression when NTera2 cells were simultaneously transfected with pcDNA3.1-AXIN1+siAXIN1. In conclusion, the results of the present study indicate that overexpression of AXIN1 protects against TGCTs via inhibiting the PI3K/AKT/mTOR signaling pathway, suggesting that AXIN1 may be a potential target for gene therapy in TGCTs.

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Gene expression profiling of paired ovarian tumors obtained prior to and following adjuvant chemotherapy: Molecular signatures of chemoresistant tumors

Cited by 88 publications

References 42 publications

Immunohistochemical analysis of possible chemoresistance markers identified by micro-arrays on serous ovarian carcinomas

Immunohistochemical analysis of possible chemoresistance markers identified by micro-arrays on serous ovarian carcinomas

Molecular typing of epithelial ovarian carcinomas using inflammatory markers

AXIN1 protects against testicular germ cell tumors via the PI3K/AKT/mTOR signaling pathway

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