Lack of p21/Waf-1 expression and lymphocyte infiltration in primary ovarian cancer correlate with the somatic HLA-A2 expression

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21059-21059
Author(s):  
E. Andersson ◽  
L. Villabona ◽  
L. Kanter ◽  
Z. Gamzatova ◽  
R. Kiessling ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Risk Group ◽  
High Risk Group ◽  
Lymphocyte Infiltration ◽  
Serous Adenocarcinoma ◽  
Primary Ovarian Cancer ◽  
Hybridization Procedure ◽  
Oligonucleotide Hybridization ◽  
Adenocarcinoma Of The Ovary ◽  
Negative Factors

21059 Background: HLA-A2 allele is highly prevalent in Scandinavia and decreases with latitude in Europe. Similarly, ovarian cancer mortality decreases with latitude in European countries. We have previously shown that HLA-A2 is associated to a severe prognosis in serous adenocarcinoma of the ovary in stage III-IV. Others have shown that lack of p21/Waf-1 and lymphocyte infiltration in this tumour is correlated to poorer prognosis as well. Here we analyse a possible linkage between these variables. Methods: Thirty eight Swedish women with epithelial ovarian cancer were analyzed for the HLA-A genotype locus by PCR/sequence-specific oligonucleotide hybridization procedure (PCR/SSOP). Tissue slides from paraffin embedded tumour material were stained with haematoxylin and antibodies anti-p21 and -p53. Results: Twenty two patients were HLA-A2 positive. Fourteen of them (37%) lacked lymphocyte infiltration wich differed significantly from HLA-A2 negative patients (n=4, 11 %) (p=0.002). All of the HLA-A2 positive patients, with serous adenocarcinoma that showed absence of tumour lymphocyte infiltration, did not express p21/waf-1 (n=7 18 %). No cases in the HLA-A2 negative group with the same parameters were identified (p=0.009). Conclusions: These observations identify a high risk group of patients by linking together the somatic expression of HLA-A2 to the lack of lymphocyte infiltration and absence of p21/Waf-1 expression at the tumour level as prognostic negative factors. The information might have a relevant impact on the patient management.. In order to obtain a stronger power the analysis will be extended to a larger group of patients. No significant financial relationships to disclose.

Swedish ovarian cancer patients are found with a high frequency of human leucocyte antigen (HLA) A2, -B7, -B12, -B15 -B44 and -DRB1–4 haplotypes

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 20100-20100
Author(s):  
K. Bergfeldt ◽  
Z. Gamzatova ◽  
B. Tholander ◽  
M. Bergdahl ◽  
B. Nordström ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Clinical Stage ◽  
Median Frequency ◽  
High Concentration ◽  
Swedish Population ◽  
Hybridization Procedure ◽  
Comparison Results ◽  
Oligonucleotide Hybridization ◽  
Adenocarcinoma Of The Ovary

20100 Background: There is an increased interest on the association between HLA markers and prognostic outcome in several cancer forms. We have previously reported that the high prevalence of the A2 allele in Scandinavia, which decreases with latitude in Europe, correlates to a similar decrease in ovarian cancer mortality among European countries. We have also published the association of this allele with severe prognosis in serous adenocarcinoma of the Ovary in stage III-IV. We now present a complete distribution of the HLA- A, -B -C and DRB1 alleles and haplotypes in relation to histology and clinical stage. Methods: An unbiased selection of epithelial ovarian cancer patients (n = 56) recorded by age, histology, stage and treatment were analyzed for HLA-A, -B, -C and -DRB1 genotypes by PCR/sequence-specific oligonucleotide hybridization procedure (PCR/SSOP). HLA frequencies from healthy Swedish bone marrow donors were used as comparison. Results: HLA-A2, -B7, -B15, -B44 as well as the A2, -B15, -DR4 haplotypes frequency are significantly higher than in the healthy Swedish population. We noticed a high concentration of this haplotypes among the serous adenocarcinomas. Seven patients were homozygotes for A2 allele (23%), two times the healthy Swedish population (12%), and 3 times the median frequency in Europe (8%). Six of these had the haplotype -A2, -B7. Conclusions: HLA-A2 homozygotes and some HLA-A2 -B and -DRb1 haplotypes are higher expressed than in healthy individuals. These observations corroborate the relevance of HLA in association with ovarian cancer, previously partially investigated. Ongoing studies consider the relationship of HLA-A2 and its haplotypes to possible oncogenes and prognosis in ovarian cancer. No significant financial relationships to disclose.

scholarly journals Prediction of a high-risk group based on postoperative nadir CA-125 levels in patients with advanced epithelial ovarian cancer

2011 ◽  
Vol 22 (4) ◽  
pp. 269 ◽  
Author(s):  
Sokbom Kang ◽  
Tae-Joong Kim ◽  
Sang-Soo Seo ◽  
Byoung-Gie Kim ◽  
Duk-Soo Bae ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
High Risk ◽  
Epithelial Ovarian Cancer ◽  
Risk Group ◽  
High Risk Group ◽  
Ca 125 ◽  
Advanced Epithelial Ovarian Cancer

scholarly journals Pharmacogenetic score predicts overall survival, progression-free survival and platinum sensitivity in ovarian cancer

2020 ◽  
Vol 21 (14) ◽  
pp. 995-1010
Author(s):  
Sara Gagno ◽  
Michele Bartoletti ◽  
Chiara Romualdi ◽  
Elena Poletto ◽  
Simona Scalone ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Germ Line ◽  
Risk Group ◽  
Prognostic Score ◽  
Progression Free Survival ◽  
High Risk Group ◽  
Free Survival ◽  
Estrogen Activity ◽  
The Impact

Aim: To define the impact of polymorphisms in genes involved in platinum-taxane and estrogen activity in the outcome of platinum-based treated ovarian cancer patients (OCP). Patients & Methods: Two hundred and thirty OCP were analyzed for 124 germ-line polymorphisms to generate a prognostic score for overall survival (OS), progression-free survival (PFS) and platinum-free interval (PFI). Results: ABCG2 rs3219191D>I, UGT1A rs10929302G>A and UGT1A rs2741045T>C polymorphisms were significantly associated with all three parameters (OS, PFS and PFI) and were used to generate a score. Patients in high-risk group had a poorer OS (hazard ratio [HR]: 1.8; 95% CI: 1.3–2.7; p = 0.0019), PFS (HR: 2.0; 95% CI: 1.4–2.9; p < 0.0001) and PFI (HR: 1.9; 95% CI: 1.4–2.8; p = 0.0002) compared with those in low-risk group. Conclusion: The prognostic-score including polymorphisms involved in drug and estrogen pathways stratifies OCP according to OS, PFS and PFI.

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.

scholarly journals Integrated Analysis of Ferroptosis-Related Biomarker Signatures to Improve the Diagnosis and Prognosis Prediction of Ovarian Cancer

2022 ◽  
Vol 9 ◽  
Author(s):  
Huan Wang ◽  
Qi Cheng ◽  
Kaikai Chang ◽  
Lingjie Bao ◽  
Xiaofang Yi
Keyword(s):  
Ovarian Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
Risk Group ◽  
High Risk Group ◽  
The Cancer Genome Atlas ◽  
Integrated Analysis ◽  
M2 Macrophage ◽  
Gynecological Malignancy

Ovarian cancer remains the most lethal gynecological malignancy. Ferroptosis, a specialized form of iron-dependent, nonapoptotic cell death, plays a crucial role in various cancers. However, the contribution of ferroptosis to ovarian cancer is poorly understood. Here, we characterized the diagnostic, prognostic, and therapeutic value of ferroptosis-related genes in ovarian cancer by analyzing transcriptomic data from The Cancer Genome Atlas and Gene Expression Omnibus databases. A reliable 10-gene ferroptosis signature (HIC1, ACSF2, MUC1, etc.) for the diagnosis of ovarian cancer was identified. Notably, we constructed and validated a novel prognostic signature including three FRGs: HIC1, LPCAT3, and DUOX1. We also further developed a risk score model based on these three genes which divided ovarian cancer patients into two risk groups. Functional analysis revealed that immune response and immune-related pathways were enriched in the high-risk group. Meanwhile, the tumor microenvironment was distinct between the two groups, with more M2 Macrophage infiltration and higher expression of key immune checkpoint molecules in the high-risk group than in the other group. Low-risk patients exhibited more favorable immunotherapy and chemotherapy responses. We conclude that crosstalk between ferroptosis and immunity may contribute to the worse prognosis of patients in the high-risk group. In particular, HIC1 showed both diagnostic and prognostic value in ovarian cancer. In vitro experiments demonstrated that inhibition of HIC1 improved drug sensitivity of chemotherapy and immunotherapy agents by inducing ferroptosis. Our findings provide new insights into the potential role of FRGs in the early detection, prognostic prediction, and individualized treatment decision-making for ovarian cancer patients.

scholarly journals Construction of a Macrophage Infiltration Regulatory Network and Related Prognostic Model of High-Grade Serous Ovarian Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Hua Chang ◽  
Yuyan Zhu ◽  
Jiahui Zheng ◽  
Lian Chen ◽  
Jiaxing Lin ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Prognostic Model ◽  
Risk Group ◽  
High Risk Group ◽  
Macrophage Infiltration ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
M1 Macrophages ◽  
High Infiltration

Background. High-grade serous ovarian cancer (HGSOC) carries the highest mortality in the gynecological cancers; however, therapeutic outcomes have not significantly improved in recent decades. Macrophages play an essential role in the occurrence and development of ovarian cancer, so the mechanisms of macrophage infiltration should be elucidated. Method. We downloaded transcriptome data of ovarian cancers from the Gene Expression Omnibus and The Cancer Genome Atlas. After rigorous screening, 1566 HGSOC were used for data analysis. CIBERSORT was used to estimate the level of macrophage infiltration and WGCNA was used to identify macrophage-related modules. We constructed a macrophage-related prognostic model using machine learning LASSO algorithm and verified it using multiple HGSOC cohorts. Results. In the GPL570-OV cohort, high infiltration level of M1 macrophages was associated with a good outcome, while high infiltration level of M2 macrophages was associated with poor outcomes. We used WGCNA to select genes correlated with macrophage infiltration. These genes were used to construct protein-protein interaction maps of macrophage infiltration. IFL44L, RSAD2, IFIT3, MX1, IFIH1, IFI44, and ISG15 were the hub genes in the network. We then constructed a macrophage-related prognostic model composed of CD38, ACE2, BATF2, HLA-DOB, and WARS. The model had the ability to predict the overall survival rate of HGSOC patients in GPL570-OV, GPL6480-OV, TCGA-OV, GSE50088, and GSE26712. In exploring the immune microenvironment, we found that CD4 memory T cells and activated mast cells showed that the degree of infiltration was higher in the high-risk group, while M1 macrophages were the opposite, and HLA molecules were overexpressed in the high-risk group. Conclusion. We constructed a macrophage infiltration-related protein interaction network that provides a basis for studying macrophages in HGSOC. Our macrophage-related prognostic model is robust and widely applicable. It predicts overall survival in HGSOC patients and may improve HGSOC treatment.

scholarly journals A Nine-Immune-Related Gene Prognostic Signature for Predicting Outcomes in High-Grade Serous Ovarian Cancer

2021 ◽  
Author(s):  
Yahui Jiang ◽  
Tianjiao Lyu ◽  
Tianyu Zhou ◽  
Yiwen Shi ◽  
Weiwei Feng
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Cox Regression ◽  
Risk Group ◽  
High Risk Group ◽  
Low Risk ◽  
Risk Scores ◽  
High Grade ◽  
Lasso Regression ◽  
Prognostic Signature

Abstract Background: Recently, immune system has been shown to be indispensable for ovarian cancer progression. The key immune-related genes (IRGs) related to the overall survival of ovarian cancer patients should be taken seriously. Here, we screened 9 survival-related IRGs in high-grade serous ovarian cancer (HGSOC) and build a prognostic signature to predict the outcome of HGSOC patients.Methods: We downloaded RNA-sequence profiles from The Cancer Genome Atlas (TCGA) and Genome Tissue Expression (GTEx) databases to identify differentially expressed genes between normal fallopian tube and HGSOC. Among these genes, IRGs were filtered based on the Immunology Database and Analysis Portal (ImmPort). Using univariate Cox regression, Lasso regression and multivariate Cox regression, we selected 9 survival-related IRGs and established a prognostic signature to compute the risk score. Patients were divided into a low-risk group and a high-risk group, and the immunological feature differences between them were analysed with the ESTIMATE R package, TIMER and GSEA software. Moreover, the prognostic signature was validated by data from Gene Expression Omnibus (GEO) datasets.Results: We obtained 1544 differentially expressed genes in HGSOC compared with normal fallopian tube, among which 99 genes were related to immunology. After univariate Cox regression, Lasso regression and multivariate Cox regression, nine IRGs (HLA-F, PSMC1, PI3, CXCL10, CXCL9, CXCL11, LRP1, STAT1 and OGN) were identified as optimal survival-related IRGs and used to establish a prognostic signature for calculating the risk scores of HGSOC patients. The prognostic signature showed its efficiency in predicting the overall survival of HGSOC patients in TCGA training cohort (p=1.018e-8) and GEO test cohort (p=2.632e-2). Age and risk scores were independent risk factors for overall survival. As the risk scores increased, the proportions of neutrophil, dendritic cells, CD8+ T cells, CD4+ T cells and B cells decreased (p values were 0.026, 1.909e-4, 9.165e-10, 0.003 and 2.658e-4, respectively). In addition, 21 out of 24 HLA-related genes were highly expressed in the low-risk group than in the high-risk group. The above might prompt a stronger immune response in the low-risk group.Conclusions: Our study constructed a nine-IRG-based prognostic signature that could effectively predict the overall survival of HGSOC patients and become a promising therapeutic target for HGSOC treatments.

Characteristics of hematopoiesis in primary and recurrent ovarian cancer

2021 ◽  
pp. 39-45
Author(s):  
S. V. Chulkova ◽  
A. M. Kozhonalieva ◽  
I. S. Stylidi ◽  
I. V. Poddubnaya ◽  
A. D. Palladina ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Bone Marrow ◽  
Deep Understanding ◽  
Recurrent Ovarian Cancer ◽  
The Body ◽  
High Grade ◽  
Serous Adenocarcinoma ◽  
Primary Ovarian Cancer ◽  
Metastatic Lesions ◽  
Central Organ

Introduction. An important aspect of cancer treatment today is the concept of immuno-targeted therapy, which requires a deep understanding of the characteristics of immune reactions in the body of a cancer patient. Bone marrow is the central organ of immunopoiesis, therefore, along with the study of tumor characteristics, attention is paid to the bone marrow. The study of the cellular composition of the bone marrow in some types of cancer revealed a number of features of hematopoiesis, which requires further deeper analysis.Purpose. To study the parameters of hematopoiesis in patients with primary and recurrent ovarian cancer.Materials and methods. The paper presents data from 68 patients with a verified diagnosis of primary (n = 43) and recurrent (n = 25) ovarian cancer. The study was dominated by serous adenocarcinoma of high grade. Stage I was established in 13.2 % of cases, II – in 5.9 %, III – in 60.3 %, IV – in 20.6 %. The bone marrow was harvested by puncture of the posterior iliac spine (spina iliaca posterior superior). Parameter assessment and myelogram calculation were performed by two physicians, morphologists. The content of myelokaryocytes, indicators of granulocyte, erythroid lineage, the content of lymphocytes, monocytes were analyzed, and myelogram indices were assessed. In all patients microscopy of bone marrow samples excluded metastatic lesions. Statistical data processing was performed using the SPSS Statistics v. 21 package.Results. The analysis of bone marrow samples from patients with ovarian cancer revealed differences with the norm for both primary and recurrent ovarian cancer. Most punctates were normocellular, but average myelokaryocyte count in both groups was below normal. With recurrent ovarian cancer, a reduced content of promyelocytes and metamyelocytes was noted, whereas with primary cancer, all young forms of neutrophils was below normal. An increase in segmented neutrophils without a change in the percentage of cells of the granulocytic lineage was observed in primary ovarian cancer, and in one third of the samples of bone marrow an increased number lymphocytes and monocytes were noted. With recurrent ovarian cancer lymphocytes were increased in 2/3 of samples, monocyte – in 48 %. A change in the proportion of cells of the erythroid lineage was observed in both recurrent and primary cancers: depletion of the pool of basophilic normoblasts and polychromatophils with an unchanged number of erythrokaryocytes, an increase in oxyphilic forms were noted.Conclusion. The revealed changes in hematopoiesis in ovarian cancer reflect the aggressive course of high-grade tumors, which can be considered as a result of the systemic influence of the tumor, and the obtained data can serve as the basis for a detailed immunophenotypic study of bone marrow in ovarian cancer.

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