scholarly journals Consensus on Molecular Subtypes of Ovarian Cancer

2017 ◽  
Author(s):  
Gregory M Chen ◽  
Lavanya Kannan ◽  
Ludwig Geistlinger ◽  
Victor Kofia ◽  
Zhaleh Safikhani ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ovarian Cancer ◽  
Overall Survival ◽  
Molecular Subtypes ◽  
Meta Analysis ◽  
Gene Signature ◽  
Ovarian Tumors ◽  
Fitting In ◽  
Microarray Datasets

AbstractINTRODUCTIONVarious computational methods for gene expression-based subtyping of high-grade serous (HGS) ovarian cancer have been proposed. This resulted in the identification of molecular subtypes that are based on different datasets and were differentially validated, making it difficult to achieve consensus on which definitions to use in follow-up studies. We assess three major subtype classifiers for their robustness and association to outcome by a meta-analysis of publicly available expression data, and provide a classifier that represents their consensus.METHODSWe use a compendium of 15 microarray datasets consisting of 1,774 HGS ovarian tumors to assess 1) concordance between published subtyping algorithms, 2) robustness of those algorithms to re-clustering across datasets, and 3) association of subtypes with overall survival. A consensus classifier is trained on concordantly classified samples, and validated by leave-one-dataset-out validation.RESULTSEach subtyping classifier identified subsets significantly differing in overall survival, but were not robust to re-fitting in independent datasets and grouped only approximately one third of patients concordantly into four subtypes. We propose a consensus classifier to identify the minority of unambiguously classifiable tumors across multiple gene expression platforms, using a 100-gene signature. The resulting consensus subtypes correlate with patient age, survival, tumor purity, and lymphocyte infiltration.CONCLUSIONSOur analysis demonstrates that most HGS ovarian cancers are not able to be subtyped. A minority of tumors can be classified and our proposed consensus classifier consolidates and improves on the robustness of three previously proposed subtype classifiers. It provides reliable stratification of patients with HGS ovarian tumors of clearly defined subtype, and will assist in studying the role of polyclonality in the majority of tumors that are not robustly classifiable.

scholarly journals The prognostic role of microRNA in epithelial ovarian cancer: a systematic review of literature with an overall survival meta-analysis

Oncotarget ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 1085-1095 ◽  
Author(s):  
Patricia Ferreira ◽  
Rosimeire Aparecida Roela ◽  
Rossana Veronica Mendoza Lopez ◽  
Maria Del Pilar Estevez-Diz
Keyword(s):  
Systematic Review ◽  
Ovarian Cancer ◽  
Overall Survival ◽  
Epithelial Ovarian Cancer ◽  
Meta Analysis ◽  
Review Of Literature ◽  
Prognostic Role

The role of proinflammatory immune (IFN-gamma) gene signature in predicting prognosis and response to chemotherapy in uterine carcinoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14209-e14209
Author(s):  
Haider Mahdi ◽  
Peter Graham Rose ◽  
Fadi W Abdul-Karim ◽  
Bradley J. Monk ◽  
Ying Ni
Keyword(s):  
Gene Expression ◽  
Ovarian Cancer ◽  
Overall Survival ◽  
T Cells ◽  
Progression Free Survival ◽  
Gene Signature ◽  
Free Survival ◽  
High Stage ◽  
Response To Chemotherapy ◽  
Ifn Γ

e14209 Background: Immunotherapy is promising option given low toxicity and potential durable response. In mismatch repair proficient endometrial and ovarian cancers, the reported response rate is ranging from 10-15% in recurrent setting. We need to better identify subset of patients who benefits from immunotherapy. Multigene immune signatures represent a robust means of capturing a complex, T cell–inflamed phenotype necessary for the clinical activity of PD-1–/PD-L1–directed monoclonal antibodies. IFN-γ is a key cytokine produced by activated T cells, as well as natural killer (NK) and NK T cells, in the tumor microenvironment. An immune-related IFN-γ 18-gene profile was derived through a cross-validated penalized regression modeling strategy to predict response to anti-PD1 therapy across 9 different tumor types. We want to test if this gene panel can also predict cancer outcome and response to chemotherapy. Methods: We used whole transcriptome sequencing of RNA matched tumor-normal samples from 38 high stage (Stage III and IV) uterine serous cancer patients. All patients received chemotherapy with platinum and taxanes. IFN-18 gene expression score was calculated by averaging the normalized and log transformed individual gene read counts. The optimized score cut off was selected to best separating the progression free survival. Then the cut off score was tested in The Cancer Genomic Atlas (TCGA) uterine and ovarian cancer RNAseq datasets. Results: The IFN score of 2.46 was determined based on 18-gene expression derived from 38 high-stage uterine serous cancer samples. Average age was 67 years (range: 56-82 years). Uterine serous cancer is known to be MSI stable. Patients with score higher than 2.46 showed significantly longer progression free survival (PFS – 57.6 months vs 15months, p = 0.002) and longer overall survival (73.1 months vs 51.1 months), not statistically significant given our small sample size, p = 0.13) compared to the patients with score lower than 2.46. Then this IFN based gene signature was then applied to TCGA 541 uterine cancer samples with RNAseq data. Similarly, this signature predicted significant improvement in both progression-free survival (p = 0.001) and overall survival (p = 0.005). Interestingly, this score cannot separate outcome for TCGA ovarian cancer cohort. Conclusions: Immune-related IFN-γ gene signature predicted prognosis and response to chemotherapy. We plan to assess if this signature will predict endometrial cancer patients who benefits from anti-PD1 therapy.

The role of altered long noncoding RNAs in overall survival of ovarian cancer: A systematic review and meta-analysis

2021 ◽  
Vol 219 ◽  
pp. 153363
Author(s):  
Elahe Seyed Hosseini ◽  
Marziyeh Alizadeh Zarei ◽  
Hamed Haddad Kashani ◽  
Alireza Milajerdi ◽  
Zahra Zare Dehghanani ◽  
...  
Keyword(s):  
Systematic Review ◽  
Ovarian Cancer ◽  
Overall Survival ◽  
Meta Analysis ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas

scholarly journals Comparison of the survival outcomes of laparoscopy versus laparotomy in treatment of early-stage ovarian cancer: a systematic review and meta-analysis

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Qingduo Kong ◽  
Hongyi Wei ◽  
Jing Zhang ◽  
Yilin Li ◽  
Yongjun Wang
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Early Stage ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Cochrane Library ◽  
Survival Outcomes ◽  
Free Survival ◽  
Review Manager ◽  
Early Stage Ovarian Cancer

Abstract Background Laparoscopy has been widely used for patients with early-stage epithelial ovarian cancer (eEOC). However, there is limited evidence regarding whether survival outcomes of laparoscopy are equivalent to those of laparotomy among patients with eEOC. The result of survival outcomes of laparoscopy is still controversial. The aim of this meta-analysis is to analyze the survival outcomes of laparoscopy versus laparotomy in the treatment of eEOC. Methods According to the keywords, Pubmed, Embase, Cochrane Library and Clinicaltrials.gov were searched for studies from January 1994 to January 2021. Studies comparing the efficacy and safety of laparoscopy versus laparotomy for patients with eEOC were assessed for eligibility. Only studies including outcomes of overall survival (OS) were enrolled. The meta-analysis was performed using Stata software (Version 12.0) and Review Manager (Version 5.2). Results A total of 6 retrospective non-random studies were included in this meta-analysis. The pooled results indicated that there was no difference between two approaches for patients with eEOC in OS (HR = 0.6, P = 0.446), progression-free survival (PFS) (HR = 0.6, P = 0.137) and upstaging rate (OR = 1.18, P = 0.54). But the recurrence rate of laparoscopic surgery was lower than that of laparotomic surgery (OR = 0.48, P = 0.008). Conclusions Laparoscopy and laparotomy appear to provide comparable overall survival and progression-free survival outcomes for patients with eEOC. Further high-quality studies are needed to enhance this statement.

scholarly journals Prognostic Role of MicroRNAs in Human Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis

2018 ◽  
Vol 2018 ◽  
pp. 1-17 ◽  
Author(s):  
Shree Ram Lamichhane ◽  
Thanuja Thachil ◽  
Paolo De Ieso ◽  
Harriet Gee ◽  
Simon Andrew Moss ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Subgroup Analysis ◽  
Meta Analysis ◽  
Small Cell ◽  
Cancer Tissue ◽  
Small Cell Lung

Background. MicroRNAs (miRNAs) have been found to play an important role in the development and outcomes for multiple human cancers. Their role as a prognostic biomarker in non-small-cell lung cancer (NSCLC) remains unclear. This meta-analysis aims to clarify the role of various miRNAs in the survival of NSCLC patients. Materials and Methods. All studies were identified through medical database search engines. A meta-analysis was conducted to assess the correlation between miRNAs expressions and overall survival among those NSCLC studies. Relevant data were extracted from each eligible study regarding baseline characteristics and key statistics such as hazard ratio (HR), 95% confidence interval (CI), and P value, which were utilized to calculate a pooled effect size. Result. Thirty-two studies were included in the meta-analysis. Using a random effect model, the combined HR and 95% CI for overall survival (OS) was calculated as 1.59 (1.39–1.82), predicting a poor overall survival. Five miRNAs (miR-21, miR-155, miR-let-7, miR-148a, and miR-148b) were found to be of significance for predicting OS in at least two studies, hence, selected for subgroup analysis. Subgroup analysis disclosed that elevated levels of miR-21 and miR-155 in both cancer tissue and blood samples were associated with worse OS. Compared to American studies (I-squared: <0.001% and P value: 0.94), Asian and European studies exhibited greater heterogeneity in miRNA expression and relationship to OS (I-squared, P values were approximately 78.85%, <0.001 and 61.28%, 0.006, respectively). These subgroup analyses also highlighted that elevated expression of miR-21 and miR-155 and low levels of expression of miR-148a, miR-148b, and miR-let-7 were associated with poor prognosis in NSCLC. Conclusion. miR-21, miR-155, miR-148a, miR-148b, and miR-let-7 are consistently up- or downregulated in NSCLC and are associated with poor OS. These miRNAs show potential as useful prognostic biomarkers in the diagnosis, treatment, and follow-up of NSCLC.

scholarly journals The forkhead box L2 transcription factor (FOXL2) is differentially expressed in high-grade serous ovarian cancers.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Gene Expression ◽  
Ovarian Cancer ◽  
Expression Profiles ◽  
Gynecologic Cancer ◽  
Ovarian Tumors ◽  
High Grade ◽  
Normal Ovary ◽  
Primary Tumors ◽  
Forkhead Box ◽  
Ovarian Cancers

Ovarian cancer is the most lethal gynecologic cancer (1). We sought to identify genes associated with high-grade serous ovarian cancer (HGSC) by comparing global gene expression profiles of normal ovary with that of primary tumors from women diagnosed with HGSC using published microarray data (2, 3). We identified the forkhead box L2, (FOXL2) (4) as among the genes whose expression was most different in HGSC ovarian tumors. FOXL2 expression was significantly lower in ovarian tumors relative to normal ovary. FOXL2 has established roles in ovarian development (4, 5), and the FOXL2 gene is mutated in granulosa-cell tumors of the ovary (6). These data indicate FOXL2 might also be perturbed, at the level of gene expression, in high-grade serous ovarian cancers.

MYC as a candidate upstream controller involved in TYMS gene expression and 5-FU/folate treatment efficacy in colorectal cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15512-e15512
Author(s):  
David A. Drubin ◽  
Anne-Katrin Hess ◽  
Natalie L. Catlett ◽  
Alessandro Di Cara ◽  
Yvonne Wettergren ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Immune Cell ◽  
Stage Iv ◽  
Gene Signature ◽  
Immune Cell Population ◽  
Potential Biomarker ◽  
Cancer Genome Atlas ◽  
Classical Monocytes

e15512 Background: One of the target enzymes of 5-fluorouracil (5-FU)-based therapies is thymidylate synthase (TS) encoded by the TYMS gene. To enhance the effect of 5-FU, a folate analogue is often provided as part of the treatment. In this context, it has previously been shown in the ISO-CC-005 clinical study that TYMS gene expression can be predictive of response to 5-FU + folate analogue Arfolitixorin. Methods: To better understand the role of TYMS expression as a predictor of response to 5-FU + folate-based therapies and identify potential mechanisms and biomarkers of sensitivity/resistance, we leveraged data from the publicly available cancer genome atlas database (TCGA). We combined this information with a knowledgebase of causal biological relationships extracted from peer reviewed publications, to identify other relevant genes and candidate upstream controllers directly or indirectly related to TYMS expression and 5-FU + folate efficacy. Results: In TCGA subjects suffering from colorectal cancer (CRC) (stage IV tumors, treated with FOLFOX/FOLFIRI (n = 38)), lower TYMS expression was associated with a better overall survival (OS). This is consistent with what has been observed in the ISO-CC-005 study. Applying our causal biology knowledgebase to both genes identified as correlated to TYMS expression in TCGA CRC tumors and other published sets of genes associated with FOLFOX or FOLFIRI efficacy, we identified overlap with a MYCN signature. Notably MYC has been shown to directly activate TYMS expression. Thus, the MYC family is a compelling candidate upstream controller of these genes. We scored TCGA CRC tumors for inferred MYC activity, using this MYCN gene signature, and evaluated the inferred activity with respect to OS. In stage IV tumors, higher inferred MYC activity appears to be associated with worse OS. To further characterize this inferred MYC activity, we employed a transcriptomics-based cell deconvolution estimation of immune cell population proportions in the TCGA CRC cohort. We found inferred MYC activity inversely correlated with immune cell proportions overall, specifically strongest with those of pDCs and classical monocytes. Conclusions: MYC activation, a known transcriptional regulator of TYMS, has been identified as a potentially relevant common upstream controller of a group of genes involved in 5-FU + folate analogue efficacy. Here we have also observed a similar relationship to OS between TYMS and inferred MYC activity in Stage IV CRC. MYC family activity (and activated protein forms), genes of the MYCN signature, or the identified immune cell proportions are all potential biomarker candidates to explore as factors in 5-FU + folate analogue efficacy.

Development and validation of an unfolded protein response-related gene signature to predict overall survival in HNSCC.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18033-e18033
Author(s):  
Jun Chen ◽  
Bei Zhang
Keyword(s):  
Gene Expression ◽  
Overall Survival ◽  
Unfolded Protein Response ◽  
Cox Regression ◽  
Risk Group ◽  
Gene Signature ◽  
Related Gene ◽  
Hallmarks Of Cancer ◽  
Unfolded Protein ◽  
Protein Response

e18033 Background: Genomic expression profiles have enabled the classification of head and neck squamous cell carcinoma (HNSCC) into molecular sub-types and provide prognostic information, which have implications for the personalized treatment of HNSCC beyond clinical and pathological features. Methods: Gene-expression profiling was identified in TCGA- HNSCC (n = 492) and validated with the Gene Expression Ominibus (GEO) dataset(n = 270) for which RNA sequencing data and clinical covariates were available. A single-sample gene set enrichment analysis (ssGSEA) algorithm were used to quantified the levels of various hallmarks of cancer. And LASSO Cox regression model was used to screen robust prognostic biomarkers to identify the best set of survival-associated gene signatures in HNSCC. Statistical analyses were performed using R version 3.4.4. Results: We identified unfolded protein response as the primary risk factor for survival（cox coefficient = 17.4 [8.4-26.3], P < 0.001）among various hallmarks of cancer in TCGA- HNSCC. And unfolded protein response ssGESA scores were significantly elevated in patients who died during follow up (P = 0.009). Kaplan-Meier analysis showed that patients with low ssGSEA scores of unfolded protein response exhibited better OS (HR = 0.69, P = 0.008). And we established an unfolded protein response-related gene signature based on lasso cox. We then apply the unfolded protein response -related gene signature to classify patients into the high risk group and the low risk group with the cutoff of 0.18. Adjusted for stage，age，gender, our signature was an independent risk factor for overall survival in TCGA cohorts (HR = 0.39 [0.28-0.53],P = < 0.001). In external independent cohorts, similar results were observed. In the validation cohort GEO65858, the patients with high unfolded protein response score showed longer survival (HR = 0.62 [0.38-1.0], P = 0.049). And adjusted for stage，age，HPV state, the multivariate cox regression analysis showed that unfolded protein response-related gene signature exhibited an independent risk prediction for overall survival in 270 patients with HNSCC (HR = 0.57 [0.35-0.94], P = 0.026). Conclusions: By analyzing the gene-expression data with bioinformation approach, we developed and validated a risk prediction model with unfolded protein response -related expression scores in HNSCC, which have the potential to identify patients who could have better overall survival.

scholarly journals Circulating MicroRNAs as Prognostic Molecular Biomarkers in Human Head and Neck Cancer: A Systematic Review and Meta-Analysis

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Shree Ram Lamichhane ◽  
Thanuja Thachil ◽  
Harriet Gee ◽  
Natalie Milic
Keyword(s):  
Systematic Review ◽  
Overall Survival ◽  
Head And Neck Cancer ◽  
Head And Neck ◽  
Cancer Patients ◽  
Neck Cancer ◽  
Meta Analysis ◽  
Prognostic Role ◽  
Circulating Micrornas

Background. Circulating microRNAs (miRNAs) are potential molecular biomarkers for cancer detection; however, little is known about their prognostic role in head and neck cancer. This current study is aimed at evaluating the role of novel miRNAs in the survival of head and neck cancer patients. Materials and Methods. We performed a systematic literature search using online databases for articles published between December 2006 and February 2019. A meta-analysis was conducted to assess the correlation between miRNA expressions and overall survival (OS) among the selected head and neck cancer studies. After multilevel screening by reviewers, meta-analysis was performed using hazard ratios (HR) and associated 95% confidence interval (CI) of survival to calculate a pooled effect size. Result. A total of 1577 patients across 13 studies were included in the literature review, with 18 miRNAs upregulated and 4 miRNAs downregulated predicting a poor overall survival. The forest plot generated using cumulated survival data resulted in a pooled HR value of 2.943 (95% CI: 2.394-3.618) indicating a strong association of dysregulated miRNA expression with a poor outcome. Only 2 miRNAs—low levels of miR-9 and high levels of miR-483-5p—were observed in two studies, both showing a significant association with overall cancer survival. Conclusion. To our knowledge, this is the first comprehensive systematic review and meta-analysis that examines the prognostic role of circulating miRNAs from blood in head and neck cancer patients. The combined effect estimates a HR across multiple studies and also supports the previous individual findings that an alteration in miRNA expression is highly associated with poor prognosis. This has the potential to use serum and/or plasma miRNAs as biomarkers and become novel tools for predicting the prognosis of head and neck cancer patients in the near future.

Sign in / Sign up

Export Citation Format

Share Document