Immune-related gene expression profiling of Epithelial Ovarian Cancer after Neoadjuvant chemotherapy
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE181597 | GEO | 2022/01/27
REPOSITORIES: GEO
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Project description:In the last decades platinum-based neo-adjuvant chemotherapy (NACT) has been recognized as a reliable therapeutic strategy in patients with un-resectable advanced epithelial ovarian cancer (EOC). However, the molecular changes induced by NACT at miRNA level, and their prognostic role has not been clarified until now. In order to uncover miRNAs that are altered in EOC tumor which received NACT, we performed whole-miRNA analysis on 82 FIGO Stage IIIC-IV high-grade serous (HGS) tumors, whose samples had been collected at complete primary debulking (PDS) and at interval-debulking surgery (IDS) after fter 4 courses of NACT.
2016-01-20 | E-MTAB-3696 | biostudies-arrayexpress
Project description:Optimal cytoreduction to no residual disease (R0) correlates with improved disease outcome in the management of high-grade serous ovarian cancer (HGSOC) patients. Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) offers an alternate approach to management of HGSOC patients to achieve complete resection. This study assessed proteomic alterations in matched, chemotherapy naïve and NACT-treated patients tumors obtained from HGSOC patients with suboptimal (R1) versus optimal (R0) debulking at IDS. We describe distinct proteome profiles in pre- and post-NACT HGSOC tumors correlating with residual disease status providing prognostic biomarkers for residual disease at IDS as well as candidate proteins associated with NACT resistance warranting further pre-clinical investigation.
2022-10-05 | PXD031929 | Pride
Project description:Ovarian cancer is a difficult-to-treat malignancy with a high recurrence rate of 70–80% in the late stage and 20–25% in the early stage. Primary debulking surgery (PDS) or interval debulking surgery (IDS), followed by platinum-based adjuvant chemotherapy, is the standard of care for ovarian cancer. Patients with ovarian cancer who underwent PDS or IDS for a newly diagnosed disease, diagnostic laparoscopy, or secondary debulking for a recurrent disease at the Yonsei Cancer Center, Seoul, Republic of Korea, were prospectively recruited between October 2019 and March 2022 (NCT 05504174). For the non-cancer control group, patients who underwent surgery for a suspicious ovarian mass with a CA-125 level of > 35 U/mL were enrolled. Patients with ovarian cancer received adjuvant therapy based on the current standard of care as clinicians were blinded to the ctDNA results. We aimed to assess the clinical utility of ctDNA testing using tumor-naïve, small-sized next-generation sequencing (NGS) panels. A total of 296 patients, including 201 with ovarian cancer and 95 with benign or borderline disease, were enrolled. Patients received adjuvant therapy based on the current standard of care. Cell-free DNA was extracted and sequenced using an NGS panel of nine genes: TP53, BRCA1, BRCA2, ARID1A, CCNE1, KRAS, MYC, PIK3CA, and PTEN.
2023-11-23 | E-MTAB-13555 | biostudies-arrayexpress
Project description:Pemetrexed is a drug largely used in lung cancer, mesothelioma and proposed in some cases of ovarian cancers, a particularly severe cancer type. In this latest tumor type, therapy relies on debulking surgery and platinum-based chemotherapy. Despite the initial high response rates to platinum drugs, most patients relapse and die from the disease. Considering the high levels of thymidylate synthase, dhydrofolate reductase and other folate related proteins in platinum drug resistant patients, pemetrexed was proposed as a second line drugs due to its known mechanism of action that engage the mentioned proteins. However a successful outcome could only be expected on the basis of patients’ stratifications. In the present study, a discovery proteomics approach was applied to tissue samples collected beforepemetrexed treatment from platinum resistant patients who relapsed after the first-line carboplatin-based chemotherapy but responded differently to the pemetrexed treatment.
2018-06-06 | PXD007056 | Pride
Project description:The diversity and heterogeneity within high-grade serous ovarian cancer (HGSC) is not well understood. Comprehensive molecular analyses were performed including high-pass whole-genome sequencing, targeted deep DNA sequencing, RNA sequencing, reverse-phase protein arrays, mass spectrometry-based proteomics and phosphoproteomics, and immune profiling on primary and metastatic sites from highly clinically annotated HGSC samples. Samples were obtained pre-treatment based on a laparoscopic triage algorithm from patients who underwent R0 tumor debulking or received neoadjuvant chemotherapy (NACT) with excellent or poor response.
2020-05-27 | PXD014980 | Pride
Project description:Neoadjuvant chemotherapy (NACT) followed by radical surgery for patients in FIGO stages IB2-IIB has proven to reduce tumor volume and numbers. However, NACT followed by radical surgery has not been found to improve overall survival. In this study, 35 paired pre/post-NACT cervical cancer tissues and 167 cervical cancer samples were examined by immunohistochemical analysis, SLUG expression was potentially increased in cervical cancer tissues after neoadjuvant chemotherapy, which in turn positively correlated with pelvic lymph node metastasis. The expression of SLUG following neoadjuvant chemotherapy was identified as a poor survival indicator. Functional assays, Agilent microarray hybridization and CHIP assay were performed to determine SLUG’s downstream genes and pathways. SLUG overexpression promoted metastasis in cervical cancer in both in vitro and in vivo models, whereas SLUG silencing had the opposite effect. Mechanically, SLUG is not a prerequisite for EMT activation in cervical cancer models, but contributes to the invasiveness and metastasis of cervical cancer cells by directly tethering to the recognition sequence GCCAGGTGC in the MMP3 promoter region. Our results provide mechanistic insight into the potential pro-cancer effect of neoadjuvant chemotherapy, and demonstrates that the SLUG-MMP3 axis could serve as a target for improving the efficacy of chemotherapy.
2020-12-11 | GSE163002 | GEO
Project description:PURPOSE: We investigated whether tumor tissue obtained at diagnosis expresses a specific gene profile that is predictive of findings at second-look surgery in patients with epithelial ovarian cancer (EOC). PATIENTS AND METHODS: Tumor tissue obtained at the time of diagnosis was profiled with oligonucleotide microarrays. Class prediction analysis was performed in a training set of 24 patients who had undergone a second-look procedure. The resultant predictive signature was then tested on an independent validation set comprised of 36 patients. RESULTS: A 93-gene signature referred to as the Chemotherapy Response Profile (CRP) was identified through its association with pathologic complete response. When applied to a separate validation set, the CRP distinguished between patients with unfavorable versus favorable overall survival (median 41 months v not yet reached, respectively, log-rank P = .007), with a median follow-up of 52 months. The signature maintained independent prognostic value in multivariate analysis, controlling for other known prognostic factors such as age, stage, grade, and debulking status. There was no genetic overlap between the CRP and our previously described Ovarian Cancer Prognostic Profile (OCPP), which demonstrated similar prognostic value. The combination of the CRP and OCPP yielded better prognostic discrimination then either profile alone. Genes present in the CRP include BAX, a proapoptotic protein previously associated with chemotherapy response in ovarian cancer. CONCLUSION: Identification of a gene expression profile based on pathologic response in EOC provides independent prognostic information and offers potential insights into the mechanism of drug resistance. Efforts to identify a more tailored profile using selected genes from both the CRP and OCPP are underway. keyword(s): Correlation with outcome All microarray experiments were performed at the BIDMC Genomics Center. Ovarian cancer samples were collected at the time of primary debulking surgery and frozen at 80°C. Tumor samples were pulverized in liquid nitrogen and homogenized in Trizol solution, followed by RNA isolation, probe labeling, and Affymetrix GeneChip hybridization using standard manufacturer protocols. The dChip algorithm was used for data normalization and for generating gene expression signal values. Two outlier arrays as identified by the dChip software were excluded from further analysis.
2011-08-11 | E-GEOD-31245 | biostudies-arrayexpress
Project description:The goal of the study was to identify molecular subgroups that might predict clinical outcomes in serous epithelial ovarian cancer (EOC) patients. A second objective was to identify potential therapeutic targets for serous EOC based on improved understanding of the molecular diversity of the disease. Ovarian tissues and matched peripheral blood samples were prospectively obtained from sequential patients undergoing planned gynecologic surgery at Cedars-Sinai Medical Center between 1989 and 2005. All patients underwent surgery and received adjuvant chemotherapy with a contemporaneous standard-of-care regimen.
2013-12-26 | GSE51088 | GEO
Project description:The goal of the study was to identify molecular subgroups that might predict clinical outcomes in serous epithelial ovarian cancer (EOC) patients. A second objective was to identify potential therapeutic targets for serous EOC based on improved understanding of the molecular diversity of the disease. Ovarian tissues and matched peripheral blood samples were prospectively obtained from sequential patients undergoing planned gynecologic surgery at Cedars-Sinai Medical Center between 1989 and 2005. All patients underwent surgery and received adjuvant chemotherapy with a contemporaneous standard-of-care regimen. Ovarian tissue samples (n=172) were compared to a reference pool of 106 ovarian samples. Mixed reference includes normal, benign, borderline, and malignant samples.
2013-12-26 | E-GEOD-51088 | biostudies-arrayexpress
Project description:Background: It has been shown that based on gene expression profiles, subgroups within epithelial ovarian cancers (EOC) can be identified. We studied a well characterized series of ovarian carcinomas from patients treated at our institute using gene expression profiling to better define clinically significant subgroups. Methods: Gene expression profiling was performed using RNA of 90 primary fresh frozen EOC samples representing all histological subtypes and stages (FIGO I-IV). Patients underwent either primary or interval debulking surgery and if indicated taxane-based chemotherapy. Pathology was reviewed for all cased and complete follow-up, including treatment response and recurrences was available for all patients. Results: Unsupervised and supervised analysis of gene expression data showed distinct subtypes correlating with histology. Mucinous carcinoma was the most distinct subtype based on gene expression profile. No significant differences in gene expression profile between high and low grade serous carcinomas could be observed. No gene expression signatures associated with survival or treatment response could be identified. Conclusion: Histological subtypes of ovarian adenocarcinomas are characterized by distinct gene expression profiles. In order to find signatures correlated to outcome of treatment it is essential that gene expression profiling studies are performed in histological homogeneous groups.
2023-05-18 | GSE61883 | GEO