USP19 and RPL23 as Candidate Prognostic Markers for Advanced-Stage High-Grade Serous Ovarian Carcinoma.
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ABSTRACT:
SUBMITTER: Kang H
PROVIDER: S-EPMC8391231 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Ovarian cancer is one of the leading causes of death among patients with gynecological malignancies worldwide. To identify prognostic markers for ovarian cancer, we performed RNA-sequencing and analyzed the transcriptome data from 51 patients who received conventional therapies for high-grade serous ovarian carcinoma (HGSC). Patients with early-stage (I or II) HGSC exhibited higher immune gene expression than patients with advanced stage (III or IV) HGSC. To predict the prognosis of HGSC patients, we created machine learning-based models and identified RPL23 and USP19 as candidate prognostic markers. Specifically, patients with higher RPL23 mRNA levels had a worse prognosis and patients with higher USP19 mRNA levels had a better prognosis. This model was then used to analyze HGSC patient data hosted on The Cancer Genome Atlas; this exercise validated the prognostic abilities of these two genes with respect to patient survival. Taken together, the transcriptome profiles of RPL23 and USP19 determined using a machine-learning model could serve as prognostic markers in HGSC patients receiving conventional therapy.
2021-08-09 | GSE165808 | GEO
Project description:USP19 and RPL23 as candidate prognostic markers in advanced-stage high-grade serous ovarian carcinoma
| PRJNA697947 | ENA
Project description:With regard to relapse and survival, early-stage high-grade serous ovarian (HGSOC) patients comprise a heterogeneous group and there is no clear consensus on first-line treatment. Currently, no prognostic markers are available for risk assessment by standard targeted immunohistochemistry and novel approaches are urgently required. Here, we applied MALDI-imaging mass spectrometry (MALDI-IMS), a new method to identify distinct mass profiles including protein signatures on paraffin-embedded tissue sections. In search of prognostic biomarker candidates, we compared proteomic profiles of primary tumor sections from early-stage HGSOC patients with either recurrent (RD) or non-recurrent disease (N = 4; each group) as a proof of concept study. In total, MALDI-IMS analysis resulted in 7537 spectra from the malignant tumor areas. Using receiver operating characteristic (ROC) analysis, 151 peptides were able to discriminate between patients with RD and non-RD (AUC > 0.6 or < 0.4; p < 0.01), and 13 of them could be annotated to proteins. Strongest expression levels of specific peptides linked to Keratin type1 and Collagen alpha-2(I) were observed and associated with poor prognosis (AUC > 0.7). These results confirm that in using IMS, we could identify new candidates to predict clinical outcome and treatment extent for patients with early-stage HGSOC.
| S-EPMC7463791 | biostudies-literature
Project description:Low-grade ovarian serous carcinomas are believed to arise via an adenoma-serous borderline tumor-serous carcinoma sequence. In this study, we found that advanced-stage, low-grade ovarian serous carcinomas both with and without adjacent serous borderline tumor shared similar regions of loss of heterozygosity. We then analyzed 91 ovarian tumor samples for mutations in TP53, BRAF, and KRAS. TP53 mutations were not detected in any serous borderline tumors (n = 30) or low-grade serous carcinomas (n = 43) but were found in 73% of high-grade serous carcinomas (n = 18). BRAF (n = 9) or KRAS (n = 5) mutation was detected in 47% of serous borderline tumors, but among the low-grade serous carcinomas (39 stage III, 2 stage II, and 2 stage I), only one (2%) had a BRAF mutation and eight (19%) had a KRAS mutation. The low frequency of BRAF mutations in advanced-stage, low-grade serous carcinomas, which contrasts with previous findings, suggests that aggressive, low-grade serous carcinomas are more likely derived from serous borderline tumors without BRAF mutation. In addition, advanced-stage, low-grade carcinoma patients with BRAF or KRAS mutation have a better apparent clinical outcome. However, further investigation is needed. Low-grade ovarian serous carcinomas are believed to arise via an adenoma-serous borderline tumor-serous carcinoma sequence. In this study, we found that advanced-stage, low-grade ovarian serous carcinomas both with and without adjacent serous borderline tumor shared similar regions of loss of heterozygosity. We then analyzed 91 ovarian tumor samples for mutations in TP53, BRAF, and KRAS. TP53 mutations were not detected in any serous borderline tumors (n = 30) or low-grade serous carcinomas (n = 43) but were found in 73% of high-grade serous carcinomas (n = 18). BRAF (n = 9) or KRAS (n = 5) mutation was detected in 47% of serous borderline tumors, but among the low-grade serous carcinomas (39 stage III, 2 stage II, and 2 stage I), only one (2%) had a BRAF mutation and eight (19%) had a KRAS mutation. The low frequency of BRAF mutations in advanced-stage, low-grade serous carcinomas, which contrasts with previous findings, suggests that aggressive, low-grade serous carcinomas are more likely derived from serous borderline tumors without BRAF mutation. In addition, advanced-stage, low-grade carcinoma patients with BRAF or KRAS mutation have a better apparent clinical outcome. However, further investigation is needed. Gene expression analysis was performed on five serous borderline tumors with BRAF mutation and five serous borderline tumors without BRAF mutation randomly. RNA was extracted from microdissected tumor cells. Expression profiling was carried out with Affymetrix GeneChip Human Genome U133 Plus 2.0 arrays
2011-03-04 | E-GEOD-27659 | biostudies-arrayexpress
Project description:Low-grade ovarian serous carcinomas are believed to arise via an adenoma-serous borderline tumor-serous carcinoma sequence. In this study, we found that advanced-stage, low-grade ovarian serous carcinomas both with and without adjacent serous borderline tumor shared similar regions of loss of heterozygosity. We then analyzed 91 ovarian tumor samples for mutations in TP53, BRAF, and KRAS. TP53 mutations were not detected in any serous borderline tumors (n = 30) or low-grade serous carcinomas (n = 43) but were found in 73% of high-grade serous carcinomas (n = 18). BRAF (n = 9) or KRAS (n = 5) mutation was detected in 47% of serous borderline tumors, but among the low-grade serous carcinomas (39 stage III, 2 stage II, and 2 stage I), only one (2%) had a BRAF mutation and eight (19%) had a KRAS mutation. The low frequency of BRAF mutations in advanced-stage, low-grade serous carcinomas, which contrasts with previous findings, suggests that aggressive, low-grade serous carcinomas are more likely derived from serous borderline tumors without BRAF mutation. In addition, advanced-stage, low-grade carcinoma patients with BRAF or KRAS mutation have a better apparent clinical outcome. However, further investigation is needed. Low-grade ovarian serous carcinomas are believed to arise via an adenoma-serous borderline tumor-serous carcinoma sequence. In this study, we found that advanced-stage, low-grade ovarian serous carcinomas both with and without adjacent serous borderline tumor shared similar regions of loss of heterozygosity. We then analyzed 91 ovarian tumor samples for mutations in TP53, BRAF, and KRAS. TP53 mutations were not detected in any serous borderline tumors (n = 30) or low-grade serous carcinomas (n = 43) but were found in 73% of high-grade serous carcinomas (n = 18). BRAF (n = 9) or KRAS (n = 5) mutation was detected in 47% of serous borderline tumors, but among the low-grade serous carcinomas (39 stage III, 2 stage II, and 2 stage I), only one (2%) had a BRAF mutation and eight (19%) had a KRAS mutation. The low frequency of BRAF mutations in advanced-stage, low-grade serous carcinomas, which contrasts with previous findings, suggests that aggressive, low-grade serous carcinomas are more likely derived from serous borderline tumors without BRAF mutation. In addition, advanced-stage, low-grade carcinoma patients with BRAF or KRAS mutation have a better apparent clinical outcome. However, further investigation is needed.
2011-03-04 | GSE27659 | GEO
Project description:BackgroundMechanisms of development and progression of high-grade serous ovarian cancer (HGSOC) are poorly understood. EVI1 and PARP1, part of TGF-ß pathway, are upregulated in cancers with DNA repair deficiencies with DNA repair deficiencies and may influce disease progression and survival. Therefore we questioned the prognostic significance of protein expression of EVI1 alone and in combination with PARP1 and analyzed them in a cohort of patients with HGSOC.MethodsFor 562 HGSOC patients, we evaluated EVI1 and PARP1 expression by immunohistochemical staining on tissue microarrays with QuPath digital semi-automatic positive cell detection.ResultsHigh EVI1 expressing (> 30% positive tumor cells) HGSOC were associated with improved progression-free survival (PFS) (HR = 0.66, 95% CI: 0.504-0.852, p = 0.002) and overall survival (OS) (HR = 0.45, 95% CI: 0.352-0.563, p < 0.001), including multivariate analysis. Most interestingly, mutual high expression of both proteins identifies a group with particularly good prognosis. Our findings were proven technically and clinically using bioinformatical data sets for single-cell sequencing, copy number variation and gene as well as protein expression.ConclusionsEVI1 and PARP1 are robust prognostic biomarkers for favorable prognosis in HGSOC and imply further research with respect to their reciprocity.
| S-EPMC10388497 | biostudies-literature
Project description:OBJECTIVE:To examine outcomes of patients having treatments for newly diagnosed advanced stage low-grade serous ovarian cancer (LGSC). METHODS:We conducted a retrospective case series of women affected by advanced stage (stage IIIB or more) LGSC undergoing surgery in a single oncologic center between January 2000 and December 2017. Survival outcomes were assessed using Kaplan-Meier and Cox models. RESULTS:Data of 72 patients were retrieved. Primary cytoreductive surgery was attempted in 68 (94.4%) patients: 19 (27.9%) had residual disease (RD) >1 cm after primary surgery. Interval debulking surgery (IDS) was attempted in 15 of these 19 (78.9%) patients and the remaining 4 patients having not primary debulking surgery. Twelve out of 19 (63.1%) patients having IDS had RD. After a mean (±standard deviation) follow-up was 61.6 (±37.2) months, 50 (69.4%) and 22 (30.5%) patients recurred and died of disease, respectively. Via multivariate analysis, non-optimal cytoreduction (hazard ratio [HR]=2.79; 95% confidence interval [CI]=1.16-6.70; p=0.021) and International Federation of Obstetrics and Gynecologists (FIGO) stage IV (HR=3.15; 95% CI=1.29-7.66; p=0.011) were associated with worse disease-free survival. Via multivariate analysis, absence of significant comorbidities (HR=0.56; 95% CI=0.29-1.10; p=0.093) and primary instead of IDS (HR=2.95; 95% CI=1.12-7.74; p=0.027) were independently associated with an improved overall survival. CONCLUSION:LGSC is at high risk of early recurrence. However, owing to the indolent nature of the disease, the majority of patients are long-term survivors. Further prospective studies and innovative treatment modalities are warranted to improve patients care.
| S-EPMC6304412 | biostudies-other
Project description:High-grade serous ovarian cancer (HGSOC) is an aggressive disease with different clinical outcomes and poor prognosis. This could be due to tumor heterogeneity. The 18F-FDG PET radiomic parameters permit addressing tumor heterogeneity. Nevertheless, this has been not well studied in ovarian cancer. The aim of our work was to assess the prognostic value of pretreatment 18F-FDG PET radiomic features in patients with HGSOC. A review of 36 patients diagnosed with advanced HGSOC between 2016 and 2020 in our center was performed. Radiomic features were obtained from pretreatment 18F-FDGPET. Disease-free survival (DFS) and overall survival (OS) were calculated. Optimal cutoff values with receiver operating characteristic curve/median values were used. A correlation between radiomic features and DFS/OS was made. The mean DFS was 19.6 months and OS was 37.1 months. Total Lesion Glycolysis (TLG), GLSZM_ Zone Size Non-Uniformity (GLSZM_ZSNU), and GLRLM_Run Length Non-Uniformity (GLRLM_RLNU) were significantly associated with DFS. The survival-curves analysis showed a significant difference of DSF in patients with GLRLM_RLNU > 7388.3 versus patients with lower values (19.7 months vs. 31.7 months, p = 0.035), maintaining signification in the multivariate analysis (p = 0.048). Moreover, Intensity-based Kurtosis was associated with OS (p = 0.027). Pretreatment 18F-FDG PET radiomic features GLRLM_RLNU, GLSZM_ZSNU, and Kurtosis may have prognostic value in patients with advanced HGSOC.
| S-EPMC10670627 | biostudies-literature
Project description:(1) Background: The tumor microenvironment is involved in the growth and proliferation of malignant tumors and in the process of resistance towards systemic and targeted therapies. A correlation between the gene expression profile of the tumor microenvironment and the prognosis of ovarian cancer patients is already known. (2) Methods: Based on data from The Cancer Genome Atlas (379 RNA sequencing samples), we constructed a prognostic 11-gene signature (SNRPA1, CCL19, CXCL11, CDC5L, APCDD1, LPAR2, PI3, PLEKHF1, CCDC80, CPXM1 and CTAG2) for Fédération Internationale de Gynécologie et d'Obstétrique stage III and IV serous ovarian cancer through lasso regression. (3) Results: The established risk score was able to predict the 1-, 3- and 5-year prognoses more accurately than previously known models. (4) Conclusions: We were able to confirm the predictive power of this model when we applied it to cervical and urothelial cancer, supporting its pan-cancer usability. We found that immune checkpoint genes correlate negatively with a higher risk score. Based on this information, we used our risk score to predict the biological response of cancer samples to an anti-programmed death ligand 1 immunotherapy, which could be useful for future clinical studies on immunotherapy in ovarian cancer.
| S-EPMC8268985 | biostudies-literature
Project description:To evaluate the prognostic value of fibroblast growth factor receptor 4 (FGFR4) protein expression in patients with advanced-stage, high-grade serous ovarian cancer, delineate the functional role of FGFR4 in ovarian cancer progression, and evaluate the feasibility of targeting FGFR4 in serous ovarian cancer treatment.Immunolocalization of FGFR4 was conducted on 183 ovarian tumor samples. The collected FGFR4 expression data were correlated with overall survival using Kaplan-Meier and Cox regression analyses. The effects of FGFR4 silencing on ovarian cancer cell growth, survival, invasiveness, apoptosis, and FGF1-mediated signaling pathway activation were evaluated by transfecting cells with FGFR4-specific siRNAs. An orthotopic mouse model was used to evaluate the effect of injection of FGFR4-specific siRNAs and FGFR4 trap protein encapsulated in nanoliposomes on ovarian tumor growth in vivo.Overexpression of FGFR4 protein was significantly associated with decreased overall survival durations. FGFR4 silencing significantly decreased the proliferation, survival, and invasiveness and increased apoptosis of ovarian cancer cells. Also, downregulation of FGFR4 significantly abrogated the mitogen-activated protein kinase (MAPK), nuclear factor-?B (NF-?B), and WNT signaling pathways, which are activated by FGF1. Targeting FGFR4 with the FGFR4-specific siRNAs and FGFR4 trap protein significantly decreased ovarian tumor growth in vivo.FGFR4 is a prognostic marker for advanced-stage, high-grade serous ovarian carcinoma. Silencing FGFR4 and inhibiting ligand-receptor binding significantly decrease ovarian tumor growth both in vitro and in vivo, suggesting that targeting ovarian cancer cells with high levels of FGFR4 protein expression is a new therapeutic modality for this disease and will improve survival of it.
| S-EPMC3577959 | biostudies-literature