scholarly journals Differentially methylated CpG sites associated with the high-risk group of prostate cancer

2020 ◽  
Vol 17 (4) ◽  
Author(s):  
Anastasiya Kobelyatskaya ◽  
Elena Pudova ◽  
Maria Fedorova ◽  
Kirill Nyushko ◽  
Boris Alekseev ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dna Methylation ◽  
High Risk ◽  
Risk Group ◽  
Mrna Level ◽  
High Risk Group ◽  
Response To Therapy ◽  
The Cancer Genome Atlas ◽  
Intermediate Risk ◽  
Cpg Sites

AbstractProstate cancer (PC) is one of the most common and socially significant oncological diseases among men. Bioinformatic analysis of omics data allows identifying molecular genetic changes associated with the disease development, as well as markers of prognosis and response to therapy. Alterations in DNA methylation and histone modification profiles widely occur in malignant tumors. In this study, we analyzed changes in DNA methylation in three groups of PC patients based on data from The Cancer Genome Atlas project (TCGA, https://portal.gdc.cancer.gov): (1) high- and intermediate-risk of the tumor progression, (2) favorable and unfavorable prognoses within the high-risk group, and (3) TMPRSS2-ERG-positive (tumors with TMPRSS2-ERG fusion transcript) and TMPRSS2-ERG-free cases within the high-risk group. We found eight CpG sites (cg07548607, cg13533340, cg16643088, cg18467168, cg23324953, cg23753247, cg25773620, and cg27148952) hypermethylated in the high-risk group compared with the intermediate-risk group of PC. Seven differentially methylated CpG sites (cg00063748, cg06834698, cg18607127, cg25273707, cg01704198, cg02067712, and cg02157224) were associated with unfavorable prognosis within the high-risk group. Six CpG sites (cg01138171, cg14060519, cg19570244, cg24492886, cg25605277, and cg26228280) were hypomethylated in TMPRSS2-ERG-positive PC compared to TMPRSS2-ERG-negative tumors within the high-risk group. The CpG sites were localized, predominantly, in regulatory genome regions belonging to promoters of the following genes: ARHGEF4, C6orf141, C8orf86, CLASP2, CSRNP1, GDA, GSX1, IQSEC1, MYOF, OR10A3, PLCD1, PLEC1, PRDM16, PTAFR, RP11-844P9.2, SCYL3, VPS13D, WT1, and ZSWIM2. For these genes, analysis of differential expression and its correlation with CpG site methylation (β-value level) was also performed. In addition, STK33 and PLCD1 had similar changes in colorectal cancer. As for the CSRNP1, the ARHGEF4, and the WT1 genes, misregulated expression levels were mentioned in lung, liver, pancreatic and androgen-independent prostate cancer. The potential impact of changed methylation on the mRNA level was determined for the CSRNP1, STK33, PLCD1, ARHGEF4, WT1, SCYL3, and VPS13D genes. The above CpG sites could be considered as potential prognostic markers of the high-risk group of PC.

Expression of Four Major WT1 Splicing Variants in AML and CML: Development of Quantitative Real-Time PCRs and Preliminary Results in Patient Samples.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1631-1631
Author(s):  
Tereza Lopotova ◽  
Jana Moravcova ◽  
Vaclava Polivkova ◽  
Jaroslav Polak ◽  
Jiri Schwarz ◽  
...  
Keyword(s):  
High Risk ◽  
Real Time ◽  
Risk Group ◽  
Mrna Level ◽  
High Risk Group ◽  
Response To Therapy ◽  
Target Sequence ◽  
Qrt Pcr ◽  
Splicing Variant ◽  
Splicing Variants

Abstract Abstract 1631 Poster Board I-657 WT1 expression has proved to be of prognostic significance in AML, MDS and according to our unpublished data also in CML patients. There are four major WT1 isoforms with distinct functions in cells. Splicing variants encoding the WT1 isoforms differ from each other by the presence or absence of both the exon 5 and KTS region in the exon 9 of WT1 gene. It was shown that exon 5 containing isoforms appear to cause cell cycle arrest. Therefore, differences in WT1 splicing variant ratios might be associated with prognosis and response to therapy. All currently used primer/probe systems quantify all major splicing variants as expression of total WT1. The aim of our study was to develop specific quantitative real-time PCRs (qRT-PCRs) for quantification of the four major WT1 splicing variants (+5+KTS; +5-KTS; -5+KTS; -5-KTS) at mRNA level and to apply these techniques for initial screening of WT1 splicing variants expression in AML and CML patients. We designed several sequence variants of two forward (specific for +/-5) and two reverse primers (specific for +/-KTS) and one common TaqMan probe. After in silico analyses, selected primers were subjected for testing with plasmids each carrying target sequence of the splicing variant. The qRT-PCRs were performed on RotorGene (Corbett Research). GUS was used as housekeeping gene; primers, probes and protocols were adopted from Gabert et al. (Leukemia 2003, 17:2318). Absolute quantification was applied for data evaluation (reported in percentage). Most of these tests focused on qRT-PCR specificity. The main test of quantification utility and specificity was performed by using 25 plasmid mixtures that simulate different ratios of particular variants (copies of each variant were in five different ratios to the remaining three variants; from 10/100000 to 100000/10 copies). Finally, total leukocytes from 45 AML and 13 CML patients at diagnosis were analysed to test system utility on real samples. The splicing ratio stability during the time was checked, because there were some specimens of peripheral blood not processed immediately but preserved at 4°C overnight. Our results showed high specificity and utility of all four qRT-PCRs. We were able to quantify up to 100 copies of each variant. Even in case that one of the variants was in minority compared to others in the plasmid mixture, expected number of plasmid copies was assessed by the qRT-PCR. Splicing variant ratio was found to be conserved, when the blood was preserved overnight in refrigerator. Observed differences fall within the ranges of the technical variability of the four qRT-PCRs (12-50%). In general, our preliminary data in patient samples showed the +5/-KTS variant as the most abundant in patients with CML and AML. Expression of the +5/-KTS and -5/+KTS highly varied among AML patients within the same FAB subtype. Low level of +5/+KTS variant (median 18% from total WT1) distinguished the high risk group patients (cytogenetic-based risk stratification) from the remaining groups (median 30% from total WT1). Our data also indicate that +KTS/-KTS variant expression levels independent of the presence of exon 5 may be of importance. While in low and intermediate risk groups +KTS and –KTS variants were expressed without significant differences, in the high risk group of patients the expression of –KTS variants was significantly higher. At the same time, the high risk group showed significantly decreased +5 variants levels (independent of the presence of KTS sequence). In conclusion, we have developed the specific qRT-PCRs detecting the four WT1 splicing variants on mRNA level. Further research is ongoing to confirm the aforementioned significance of different expression of the particular WT1 isoforms. Supported by MZOUHKT2005. Disclosures No relevant conflicts of interest to declare.

scholarly journals Obesity and menopause modify the epigenomic profile of breast cancer

2017 ◽  
pp. 351-363 ◽  
Author(s):  
Ana B Crujeiras ◽  
Angel Diaz-Lagares ◽  
Olafur A Stefansson ◽  
Manuel Macias-Gonzalez ◽  
Juan Sandoval ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
High Risk ◽  
Risk Group ◽  
Menopausal Status ◽  
Breast Tumors ◽  
Methylation Pattern ◽  
High Risk Group ◽  
Cpg Sites ◽  
The Impact

Obesity is a high risk factor for breast cancer. This relationship could be marked by a specific methylome. The current work was aimed to explore the impact of obesity and menopausal status on variation in breast cancer methylomes. Data from Infinium 450K array-based methylomes of 64 breast tumors were coupled with information on BMI and menopausal status. Additionally, DNA methylation results were validated in 18 non-tumor and 81 tumor breast samples. Breast tumors arising in either pre- or postmenopausal women stratified by BMI or menopausal status alone were not associated with a specific DNA methylation pattern. Intriguingly, the DNA methylation pattern identified in association with the high-risk group (postmenopausal women with high BMI (>25) and premenopausal women with normal or low BMI < 25) exclusively characterized by hypermethylation of 1287 CpG sites as compared with the low-risk group. These CpG sites included the promoter region of fourteen protein-coding genes of which CpG methylation over the ZNF577 promoter region represents the top scoring associated event. In an independent cohort, the ZNF577 promoter methylation remained statistically significant in association with the high-risk group. Additionally, the impact of ZNF577 promoter methylation on mRNA expression levels was demonstrated in breast cancer cell lines after treatment with a demethylating agent (5-azacytidine). In conclusion, the epigenome of breast tumors is affected by a complex interaction between BMI and menopausal status. The ZNF577 methylation quantification is clearly relevant for the development of novel biomarkers of precision therapy in breast cancer.

An impact of pelvic MRI (PMRI) to radiotherapy (RT) target volumes definition in prostate cancer patients (pts).

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 78-78
Author(s):  
Keren Rouvinov ◽  
Wilmosh Mermershtain ◽  
Olga Beloshicki ◽  
Shmuel Ariad ◽  
Konstantin Lavrenkov
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Risk Group ◽  
High Risk Group ◽  
Evaluation Procedure ◽  
High Dose ◽  
Intermediate Risk ◽  
Group Affiliation ◽  
High Risk Prostate Cancer ◽  
Risk Prostate Cancer

78 Background: PMRI is a standard pre-RT evaluation procedure in pts with intermediate and high-risk prostate cancer. We conducted a retrospective study to evaluate an influence of PMRI to delineation of RT clinical target volume (CTV). Methods: Medical records of prostate cancer pts treated with intensity-modulated RT (IMRT) in single institution retrieved and examined retrospectively. Initial risk group affiliation was defined using D'Amico method. PMRI reports of pts with intermediate and high-risk prostate cancer were reviewed and risk group affiliation was re-defined in regards of T- and N-stage. IMRT treatment plans were re-assessed. In regards to PMRI T-stage, extra-capsular extension (ECE) and seminal vesicles invasion (SVI) were included to high-dose CTV. Pelvic lymph nodes (PLN) were planned to treat in all high-risk pts. PLN considered pathological by PMRI were included to separate CTV to receive RT dose higher than unaffected PLN stations. Results: Between 2008 and 2014, 169 pts with intermediate and high-risk prostate cancer underwent PMRI at around 1 month before commencing IMRT. Initially, 89 pts were affiliated to intermediate-risk and 80 to high-risk group. In general, PTV-changes based on PMRI data required in 77 pts (45.5%). Thirty seven of 89 intermediate-risk pts (41.6%) have been switched to high-risk group, necessitating irradiation of PLN. ECE and SVI were included to high-dose CTV in 64 (37.8%) and 29 pts (17.2%) respectively. PLN were thought pathological in 10 pts (5.9%), which demanded contouring of a separate CTV. Conclusions: In our series PMRI-scans had a significant impact on RT target coverage decision in pts with intermediate and high-risk prostate cancer.

scholarly journals Glycolysis-Related Gene Expression Profiling Screen for Prognostic Risk Signature of Pancreatic Ductal Adenocarcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Wenjing Song ◽  
Xin He ◽  
Pengju Gong ◽  
Yan Yang ◽  
Sirui Huang ◽  
...  
Keyword(s):  
High Risk ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Risk Group ◽  
Mrna Level ◽  
High Risk Group ◽  
Low Risk ◽  
The Cancer Genome Atlas ◽  
Risk Scores ◽  
Ductal Adenocarcinoma ◽  
Related Gene

Objective: Pancreatic ductal adenocarcinoma (PDAC) is highly lethal. Although progress has been made in the treatment of PDAC, its prognosis remains unsatisfactory. This study aimed to develop novel prognostic genes related to glycolysis in PDAC and to apply these genes to new risk stratification.Methods: In this study, based on the Cancer Genome Atlas (TCGA) PAAD cohort, the expression level of glycolysis-related gene at mRNA level in PAAD and its relationship with prognosis were analyzed. Non-negative matrix decomposition (NMF) clustering was used to cluster PDAC patients according to glycolytic genes. Prognostic glycolytic genes, screened by univariate Cox analysis and LASSO regression analysis were established to calculate risk scores. The differentially expressed genes (DEGs) in the high-risk group and the low-risk group were analyzed, and the signal pathway was further enriched to analyze the correlation between glycolysis genes. In addition, based on RNA-seq data, CIBERSORT was used to evaluate the infiltration degree of immune cells in PDAC samples, and ESTIMATE was used to calculate the immune score of the samples.Results: A total of 319 glycolysis-related genes were retrieved, and all PDAC samples were divided into two clusters by NMF cluster analysis. Survival analysis showed that PDAC patients in cluster 1 had shorter survival time and worse prognosis compared with cluster 2 samples (P &lt; 0.001). A risk prediction model based on 11 glycolysis genes was constructed, according to which patients were divided into two groups, with significantly poorer prognosis in high-risk group than in low-risk group (P &lt; 0.001). Both internal validation and external dataset validation demonstrate good predictive ability of the model (AUC = 0.805, P &lt; 0.001; AUC = 0.763, P &lt; 0.001). Gene aggregation analysis showed that DEGs highly expressed in high-risk group were mainly concentrated in the glycolysis level, immune status, and tumor cell proliferation, etc. In addition, the samples in high-risk group showed immunosuppressed status and infiltrated by relatively more macrophages and less CD8+T cell.Conclusions: These findings suggested that the gene signature based on glycolysis-related genes had potential diagnostic, therapeutic, and prognostic value for PDAC.

scholarly journals SARS-CoV-2 Seroprevalence in Healthcare Workers in Germany: A Follow-Up Study

2021 ◽  
Vol 18 (9) ◽  
pp. 4540
Author(s):  
Johannes Korth ◽  
Benjamin Wilde ◽  
Sebastian Dolff ◽  
Jasmin Frisch ◽  
Michael Jahn ◽  
...  
Keyword(s):  
High Risk ◽  
Healthcare Workers ◽  
Risk Group ◽  
Close Contact ◽  
Virus Transmission ◽  
High Risk Group ◽  
Low Risk ◽  
University Hospital ◽  
Intermediate Risk ◽  
Igg Antibody

SARS-CoV-2 is a worldwide challenge for the medical sector. Healthcare workers (HCW) are a cohort vulnerable to SARS-CoV-2 infection due to frequent and close contact with COVID-19 patients. However, they are also well trained and equipped with protective gear. The SARS-CoV-2 IgG antibody status was assessed at three different time points in 450 HCW of the University Hospital Essen in Germany. HCW were stratified according to contact frequencies with COVID-19 patients in (I) a high-risk group with daily contacts with known COVID-19 patients (n = 338), (II) an intermediate-risk group with daily contacts with non-COVID-19 patients (n = 78), and (III) a low-risk group without patient contacts (n = 34). The overall seroprevalence increased from 2.2% in March–May to 4.0% in June–July to 5.1% in October–December. The SARS-CoV-2 IgG detection rate was not significantly different between the high-risk group (1.8%; 3.8%; 5.5%), the intermediate-risk group (5.1%; 6.3%; 6.1%), and the low-risk group (0%, 0%, 0%). The overall SARS-CoV-2 seroprevalence remained low in HCW in western Germany one year after the outbreak of COVID-19 in Germany, and hygiene standards seemed to be effective in preventing patient-to-staff virus transmission.

Association of pathological response to neoadjuvant pembrolizumab with tumor PD-L1 expression and high disease-free survival (DFS) in patients with resectable, local-regionally advanced, head and neck squamous cell carcinoma (HNSCC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6006-6006
Author(s):  
Trisha Michel Wise-Draper ◽  
Vinita Takiar ◽  
Michelle Lynn Mierzwa ◽  
Keith Casper ◽  
Sarah Palackdharry ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Group ◽  
Disease Free Survival ◽  
Immune Checkpoint Blockade ◽  
Skin Wound ◽  
High Risk Group ◽  
Pathological Response ◽  
Intermediate Risk ◽  
Positive Margins ◽  
Post Surgery

6006 Background: Patients with resected HNSCC, with high-risk (positive margins, extracapsular spread [ECE]) or intermediate-risk pathological features have an estimated 1-year DFS of 65% and 69%, respectively. Immune checkpoint blockade improved survival of patients with recurrent/metastatic HNSCC, and preclinical models indicate radiotherapy (RT) synergizes with anti-PD-1. Therefore, we administered the PD-1 inhibitor pembrolizumab (pembro) pre- and post-surgery with adjuvant RT +/- cisplatin in patients with resectable, locoregionally advanced (clinical T3/4 and/or ≥2 nodal metastases) HNSCC (NCT02641093). Methods: Eligible patients received pembro (200 mg I.V. x 1) 1-3 weeks before resection. Adjuvant pembro (q3 wks x 6 doses) was administered with RT (60-66Gy) with or without weekly cisplatin (40mg/m2 X 6) for patients with high-risk and intermediate-risk features, respectively. The primary endpoint was 1-year DFS estimated by Kaplan Meier curves. Safety was evaluated by CTCAE v5.0. Pathological response (PR) to neoadjuvant pembro was evaluated by comparing pre- and post-surgical tumor specimens for treatment effect (TE), defined as tumor necrosis and/or histiocytic inflammation and giant cell reaction to keratinaceous debris. PR was classified as no (NPR, < 20%), partial (PPR, ≥20% and < 90%) and major (MPR, ≥90%). Tumor PD-L1 immunohistochemistry was performed with 22c3 antibody and reported as combined positive score (CPS). Results: Ninety-two patients were enrolled. Seventy-six patients received adjuvant pembro and were evaluable for DFS. Patient characteristics included: median age 58 (range 27 – 80) years; 32% female; 88% oral cavity, 8% larynx, and 3% human papillomavirus negative oropharynx; 86% clinical T3/4 and 65% ≥2N; 49 (53%) high-risk (positive margins, 45%; ECE, 78%); 64% (44/69 available) had PD-L1 CPS ≥1. At a median follow-up of 20 months, 1-year DFS was 67% (95%CI 0.52-0.85) in the high-risk group and 93% (95%CI 0.84-1) in the intermediate-risk group. Among 80 patients evaluable for PR, TE scoring resulted in 48 NPR, 26 PPR and 6 MPR. Patients with PPR/MPR had significantly improved 1-year DFS when compared with those with NPR (100% versus 68%, p = 0.01; HR = 0.23). PD-L1 CPS ≥ 1 was not independently associated with 1-year DFS, but was highly associated with MPR/PPR (p = 0.0007). PPR/MPR in PD-L1 CPS < 1, ≥1 and ≥20, were estimated as 20, 55 and 90%, respectively. Grade ≥ 3 adverse events occurred in 62% patients with most common including dysphagia (15%), neutropenia (15%), skin/wound infections (10%), and mucositis (9%). Conclusions: PR to neoadjuvant pembro is associated with PD-L1 CPS≥1 and high DFS in patients with resectable, local-regionally advanced, HNSCC. Clinical trial information: NCT02641093.

P3609Temporal trends of the management and outcomes of patients after myocardial infarction according to the risk for recurrent cardiovascular events

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
T Grinberg ◽  
T Bental ◽  
Y Hammer ◽  
A R Assali ◽  
H Vaknin-Assa ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
High Risk ◽  
Cardiovascular Events ◽  
Risk Group ◽  
Temporal Trends ◽  
High Risk Group ◽  
Low Risk ◽  
Intermediate Risk ◽  
High Risk Patients ◽  
Risk Patients

Abstract Background Following Myocardial Infarction (MI), patients are at increased risk for recurrent cardiovascular events, particularly during the immediate period. Yet some patients are at higher risk than others, owing to their clinical characteristics and comorbidities, these high-risk patients are less often treated with guideline-recommended therapies. Aim To examine temporal trends in treatment and outcomes of patients with MI according to the TIMI risk score for secondary prevention (TRS2°P), a recently validated risk stratification tool. Methods A retrospective cohort study of patients with an acute MI, who underwent percutaneous coronary intervention and were discharged alive between 2004–2016. Temporal trends were examined in the early (2004–2010) and late (2011–2016) time-periods. Patients were stratified by the TRS2°P to a low (≤1), intermediate (2) or high-risk group (≥3). Clinical outcomes included 30-day MACE (death, MI, target vessel revascularization, coronary artery bypass grafting, unstable angina or stroke) and 1-year mortality. Results Among 4921 patients, 31% were low-risk, 27% intermediate-risk and 42% high-risk. Compared to low and intermediate-risk patients, high-risk patients were older, more commonly female, and had more comorbidities such as hypertension, diabetes, peripheral vascular disease, and chronic kidney disease. They presented more often with non ST elevation MI and 3-vessel disease. High-risk patients were less likely to receive drug eluting stents and potent anti-platelet drugs, among other guideline-recommended therapies. Evidently, they experienced higher 30-day MACE (8.1% vs. 3.9% and 2.1% in intermediate and low-risk, respectively, P<0.001) and 1-year mortality (10.4% vs. 3.9% and 1.1% in intermediate and low-risk, respectively, P<0.001). During time, comparing the early to the late-period, the use of potent antiplatelets and statins increased among the entire cohort (P<0.001). However, only the high-risk group demonstrated a significantly lower 30-day MACE (P=0.001). During time, there were no differences in 1-year mortality rate among all risk categories. Temporal trends in 30-day MACE by TRS2°P Conclusion Despite a better application of guideline-recommended therapies, high-risk patients after MI are still relatively undertreated. Nevertheless, they demonstrated the most notable improvement in outcomes over time.

scholarly journals The Impact of Preoperative Risk on the Association between Hypotension and Mortality after Cardiac Surgery: An Observational Study

2020 ◽  
Vol 9 (7) ◽  
pp. 2057
Author(s):  
Vanja Ristovic ◽  
Sophie de Roock ◽  
Thierry G. Mesana ◽  
Sean van Diepen ◽  
Louise Y. Sun
Keyword(s):  
Cardiac Surgery ◽  
Risk Factor ◽  
High Risk ◽  
Hospital Mortality ◽  
Risk Group ◽  
High Risk Group ◽  
Group Care ◽  
Intermediate Risk ◽  
Intraoperative Hypotension ◽  
The Impact

Background: Despite steady improvements in cardiac surgery-related outcomes, our understanding of the physiologic mechanisms leading to perioperative mortality remains incomplete. Intraoperative hypotension is an important risk factor for mortality after noncardiac surgery but remains relatively unexplored in the context of cardiac surgery. We examined whether the association between intraoperative hypotension and in-hospital mortality varied by patient and procedure characteristics, as defined by the validated Cardiac Anesthesia Risk Evaluation (CARE) mortality risk score. Methods: We conducted a retrospective cohort study of consecutive adult patients who underwent cardiac surgery requiring cardiopulmonary bypass (CPB) from November 2009–March 2015. Those who underwent off-pump, thoracic aorta, transplant and ventricular assist device procedures were excluded. The primary outcome was in-hospital mortality. Hypotension was categorized by mean arterial pressure (MAP) of <55 and between 55–64 mmHg before, during and after CPB. The relationship between hypotension and death was modeled using multivariable logistic regression in the intermediate and high-risk groups. Results: Among 6627 included patients, 131 (2%) died in-hospital. In-hospital mortality in patients with CARE scores of 1, 2, 3, 4 and 5 was 0 (0%), 7 (0.3%), 35 (1.3%), 41 (4.6%) and 48 (13.6%), respectively. In the intermediate-risk group (CARE = 3–4), MAP < 65 mmHg post-CPB was associated with increased odds of death in a dose-dependent fashion (adjusted OR 1.30, 95% CI 1.13–1.49, per 10 min exposure to MAP < 55 mmHg, p = 0.002; adjusted OR 1.18 [1.07–1.30] per 10 min exposure to MAP 55–64 mmHg, p = 0.001). We did not observe an association between hypotension and mortality in the high-risk group (CARE = 5). Conclusions: Post-CPB hypotension is a potentially modifiable risk factor for mortality in intermediate-risk patients. Our findings provide impetus for clinical trials to determine if hemodynamic goal-directed therapies could improve survival in these patients.

scholarly journals A novel signature of two long non-coding RNAs in BRCA mutant ovarian cancer to predict prognosis and efficiency of chemotherapy

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Yinglian Pan ◽  
Li Ping Jia ◽  
Yuzhu Liu ◽  
Yiyu Han ◽  
Qian Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
High Risk ◽  
Cox Regression ◽  
Risk Group ◽  
Gynecologic Cancer ◽  
High Risk Group ◽  
Low Risk ◽  
The Cancer Genome Atlas ◽  
Chemotherapy Treatment ◽  
Prognostic Signature

Abstract Background In this study we aimed to identify a prognostic signature in BRCA1/2 mutations to predict disease progression and the efficiency of chemotherapy ovarian cancer (OV), the second most common cause of death from gynecologic cancer in women worldwide. Methods Univariate Cox proportional-hazards and multivariate Cox regression analyses were used to identifying prognostic factors from data obtained from The Cancer Genome Atlas (TCGA) database. The area under the curve of the receiver operating characteristic curve was assessed, and the sensitivity and specificity of the prediction model were determined. Results A signature consisting of two long noncoding RNAs(lncRNAs), Z98885.2 and AC011601.1, was selected as the basis for classifying patients into high and low-risk groups (median survival: 7.2 years vs. 2.3 years). The three-year overall survival (OS) rates for the high- and low-risk group were approximately 38 and 100%, respectively. Chemotherapy treatment survival rates indicated that the high-risk group had significantly lower OS rates with adjuvant chemotherapy than the low-risk group. The one-, three-, and five-year OS were 100, 40, and 15% respectively in the high-risk group. The survival rate of the high-risk group declined rapidly after 2 years of OV chemotherapy treatment. Multivariate Cox regression associated with other traditional clinical factors showed that the 2-lncRNA model could be used as an independent OV prognostic factor. Analyses of data from the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) indicated that these signatures are pivotal to cancer development. Conclusion In conclusion, Z98885.2 and AC011601.1 comprise a novel prognostic signature for OV patients with BRCA1/2 mutations, and can be used to predict prognosis and the efficiency of chemotherapy.

Molecular Load of Pathologically Occult Metastases in Pelvic Lymph Nodes Is an Independent Prognostic Marker of Biochemical Failure After Localized Prostate Cancer Treatment

2006 ◽  
Vol 24 (19) ◽  
pp. 3081-3088 ◽  
Author(s):  
Anna C. Ferrari ◽  
Nelson N. Stone ◽  
Ralf Kurek ◽  
Elizabeth Mulligan ◽  
Roy McGregor ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Lymph Nodes ◽  
Prognostic Marker ◽  
Risk Group ◽  
High Risk Group ◽  
Biochemical Failure ◽  
Localized Prostate Cancer ◽  
Pelvic Lymph Nodes ◽  
Independent Prognostic Marker

Purpose Thirty percent of patients treated with curative intent for localized prostate cancer (PC) experience biochemical recurrence (BCR) with rising serum prostate-specific antigen (sPSA), and of these, approximately 50% succumb to progressive disease. More discriminatory staging procedures are needed to identify occult micrometastases that spawn BCR. Patients and Methods PSA mRNA copies in pathologically normal pelvic lymph nodes (N0-PLN) from 341 localized PC patients were quantified by real-time reverse-transcriptase polymerase chain reaction. Based on comparisons with normal lymph nodes and PLN with metastases and on normalization to 5 × 106 glyceraldehyde-3′-phosphate dehydrogenase mRNA copies, normalized PSA copies (PSA-N) and a threshold of PSA-N 100 or more were selected for continuous and categorical multivariate analyses of biochemical failure-free survival (BFFS) compared with established risk factors. Results At median follow-up of 4 years, the BFFS of patients with PSA-N 100 or more versus PSA-N less than 100 was 55% and 77% (P = .0002), respectively. The effect was greatest for sPSA greater than 20 ng/mL, 25% versus 60% (P = .014), Gleason score 8 or higher, 21% versus 66% (P = .0002), stage T3c, 18% versus 64% (P = .001), and high-risk group (50% v 72%; P = .05). By continuous analysis PSA-N was an independent prognostic marker for BCR (P = .049) with a hazard ratio of 1.25 (95% CI, 1.001 to 1.57). By categorical analysis, PSA-N 100 or more was an independent variable (P = .021) with a relative risk of 1.98 (95% CI, 1.11 to 3.55) for BCR compared with PSA-N less than 100. Conclusion PSA-N 100 or more is a new, independent molecular staging criterion for localized PC that identifies high-risk group patients with clinically relevant occult micrometastases in N0-PLN, who may benefit from additional therapy to prevent BCR.

Sign in / Sign up

Export Citation Format

Share Document