scholarly journals Targeted Selected Reaction Monitoring Verifies Histology Specific Peptide Signatures in Epithelial Ovarian Cancer

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5713
Author(s):  
Leena Liljedahl ◽  
Johan Malmström ◽  
Björg Kristjansdottir ◽  
Sofia Waldemarson ◽  
Karin Sundfeldt
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Clinical Symptoms ◽  
Simultaneous Detection ◽  
Selected Reaction Monitoring ◽  
Molecular Heterogeneity ◽  
Low Grade ◽  
Reaction Monitoring ◽  
High Grade ◽  
Specific Peptide

Epithelial ovarian cancer (OC) is a disease with high mortality due to vague early clinical symptoms. Benign ovarian cysts are common and accurate diagnosis remains a challenge because of the molecular heterogeneity of OC. We set out to investigate whether the disease diversity seen in ovarian cyst fluids and tumor tissue could be detected in plasma. Using existing mass spectrometry (MS)-based proteomics data, we constructed a selected reaction monitoring (SRM) assay targeting peptides from 177 cancer-related and classical proteins associated with OC. Plasma from benign, borderline, and malignant ovarian tumors were used to verify expression (n = 74). Unsupervised and supervised multivariate analyses were used for comparisons. The peptide signatures revealed by the supervised multivariate analysis contained 55 to 77 peptides each. The predictive (Q2) values were higher for benign vs. low-grade serous Q2 = 0.615, mucinous Q2 = 0.611, endometrioid Q2 = 0.428 and high-grade serous Q2 = 0.375 (stage I–II Q2 = 0.515; stage III Q2 = 0.43) OC compared to benign vs. all malignant Q2 = 0.226. With targeted SRM MS we constructed a multiplexed assay for simultaneous detection and relative quantification of 185 peptides from 177 proteins in only 20 µL of plasma. With the approach of histology-specific peptide patterns, derived from pre-selected proteins, we may be able to detect not only high-grade serous OC but also the less common OC subtypes.

scholarly journals Trace Amine-Associated Receptor 1 (TAAR1) Is a Positive Prognosticator for Epithelial Ovarian Cancer

2021 ◽  
Vol 22 (16) ◽  
pp. 8479
Author(s):  
Tilman L. R. Vogelsang ◽  
Aurelia Vattai ◽  
Elisa Schmoeckel ◽  
Till Kaltofen ◽  
Anca Chelariu-Raicu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Epithelial Ovarian Cancer ◽  
Tnm Classification ◽  
Rank Correlation ◽  
University Hospital ◽  
Cancer Tissue ◽  
Low Grade ◽  
High Grade ◽  
Trace Amine

Trace amine-associated receptor 1 (TAAR1) is a Gαs- protein coupled receptor that plays an important role in the regulation of the immune system and neurotransmission in the CNS. In ovarian cancer cell lines, stimulation of TAAR1 via 3-iodothyronamine (T1AM) reduces cell viability and induces cell death and DNA damage. Aim of this study was to evaluate the prognostic value of TAAR1 on overall survival of ovarian carcinoma patients and the correlation of TAAR1 expression with clinical parameters. Ovarian cancer tissue of n = 156 patients who were diagnosed with epithelial ovarian cancer (serous, n = 110 (high-grade, n = 80; low-grade, n = 24; unknown, n = 6); clear cell, n = 12; endometrioid, n = 21; mucinous, n = 13), and who underwent surgery at the Department of Obstetrics and Gynecology, University Hospital of the Ludwig-Maximilians University Munich, Germany between 1990 and 2002, were analyzed. The tissue was stained immunohistochemically with anti-TAAR1 and evaluated with the semiquantitative immunoreactive score (IRS). TAAR1 expression was correlated with grading, FIGO and TNM-classification, and analyzed via the Spearman’s rank correlation coefficient. Further statistical analysis was obtained using nonparametric Kruskal-Wallis rank-sum test and Mann-Whitney-U-test. This study shows that high TAAR1 expression is a positive prognosticator for overall survival in ovarian cancer patients and is significantly enhanced in low-grade serous carcinomas compared to high-grade serous carcinomas. The influence of TAAR1 as a positive prognosticator on overall survival indicates a potential prognostic relevance of signal transduction of thyroid hormone derivatives in epithelial ovarian cancer. Further studies are required to evaluate TAAR1 and its role in the development of ovarian cancer.

scholarly journals Transcriptional Characterization of Stage I Epithelial Ovarian Cancer: A Multicentric Study

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1554
Author(s):  
Enrica Calura ◽  
Matteo Ciciani ◽  
Andrea Sambugaro ◽  
Lara Paracchini ◽  
Giuseppe Benvenuto ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Stage I ◽  
Molecular Heterogeneity ◽  
Low Grade ◽  
Multicentric Study ◽  
Molecular Alterations ◽  
Molecular Features ◽  
Signaling Axis ◽  
Tumor Biopsies

Stage I epithelial ovarian cancer (EOC) represents about 10% of all EOCs. It is characterized by a complex histopathological and molecular heterogeneity, and it is composed of five main histological subtypes (mucinous, endometrioid, clear cell and high, and low grade serous), which have peculiar genetic, molecular, and clinical characteristics. As it occurs less frequently than advanced-stage EOC, its molecular features have not been thoroughly investigated. In this study, using in silico approaches and gene expression data, on a multicentric cohort composed of 208 snap-frozen tumor biopsies, we explored the subtype-specific molecular alterations that regulate tumor aggressiveness in stage I EOC. We found that single genes rather than pathways are responsible for histotype specificities and that a cAMP-PKA-CREB1 signaling axis seems to play a central role in histotype differentiation. Moreover, our results indicate that immune response seems to be, at least in part, involved in histotype differences, as a higher immune-reactive behavior of serous and mucinous samples was observed with respect to other histotypes.

scholarly journals Outcomes of Women With High-Grade and Low-Grade Advanced-Stage Serous Epithelial Ovarian Cancer

2017 ◽  
Vol 129 (3) ◽  
pp. 439-447 ◽  
Author(s):  
Allison Gockley ◽  
Alexander Melamed ◽  
Amy J. Bregar ◽  
Joel T. Clemmer ◽  
Michael Birrer ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Low Grade ◽  
High Grade ◽  
Advanced Stage ◽  
Serous Epithelial Ovarian Cancer

scholarly journals Immunohistochemical expression of p53 in Type I and II epithelial ovarian cancer among Sudanese women: a cross-sectional study

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 1739
Author(s):  
Aisha Osman Mohamed ◽  
Nazik Elmalaika Husain ◽  
Rawia Eljaili Elmassry ◽  
Lubna Alnageeb ◽  
Mohammed Elhassan ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Serous Carcinoma ◽  
Low Grade ◽  
Type I ◽  
High Grade ◽  
P53 Overexpression ◽  
Cross Sectional ◽  
Over Expression ◽  
Tumor Types

Background: Epithelial ovarian cancer (EOC) represents the leading cause of death from gynecologic malignancies worldwide. In Sudan, ovarian cancer represents the fourth most frequent tumors among females. TP53 somatic mutations is a defining feature of ovarian high-grade serous carcinoma. However, p53 sequencing is not feasible in most low- and middle-income countries, like Sudan, and its frequency varies greatly. The study aimed to determine the frequency of p53 overexpression and its relationship with tumor types I and II and tumor grade among Sudanese women with EOC. Methods: In this cross-sectional, hospital-based study a total of 114 paraffin-embedded tissue blocks previously diagnosed as epithelial ovarian cancer were collected from six governmental hospitals in Khartoum state, Sudan, in the period 2013-2016. Immunohistochemistry was performed on tissue microarray slides to measure the protein expression of p53 in the EOC. Results: Overexpression of p53 was detected in 35.1% (n=40/114) of  EOC samples, with a higher frequency in women with Type II 53.7% (n= 29/54)  than type I 18.5% (n= 10/54)  (P= 0.000). Also, a high frequency of p53 overexpression was evident in 49.2% (n= 30/61) of high-grade carcinoma compared with 16.7% (n= 1/6) of non-graded borderline tumors, and in 19.1% (n= 9/47) of low-grade tumors (P= 0.003). A high-grade serous carcinoma harbor p53 overexpression in 53.7% (n= 29/54) and none of low-grade serous carcinoma harbor p53 overexpression. Our result showed a significant association between p53 overexpression and tumor types and grades (P = 0.000 and 0.003, respectively) Conclusion:  p53 over-expression was detected in one-third of Sudanese women with EOC.  It was more common in type II EOC and high-grade serous, but negative in low-grade serous tumors. Our result showed a significant association between p53 over-expression and tumor type and grade, and can help discriminate between high- and low-grade serous carcinomas.

MOLECULAR AND GENETIC SUBTYPES OF OVARIAN CANCER: PROSPECTS FOR FURTHER STUDIES

2019 ◽  
Vol 65 (1) ◽  
pp. 56-62
Author(s):  
Alisa Villert ◽  
Larisa Kolomiets ◽  
Natalya Yunusova ◽  
Yevgeniya Fesik
Keyword(s):  
Ovarian Cancer ◽  
Ovarian Carcinoma ◽  
Molecular Subtypes ◽  
Survival Rates ◽  
Consensus Algorithm ◽  
Histopathological Diagnosis ◽  
Low Grade ◽  
High Grade ◽  
Ovarian Carcinomas ◽  
Genetic Subtypes

High-grade ovarian carcinoma is a histopathological diagnosis, however, at the molecular level, ovarian cancer represents a heterogeneous group of diseases. Studies aimed at identifying molecular genetic subtypes of ovarian cancer are conducted in order to find the answer to the question: can different molecular subgroups influence the choice of treatment? One of the achievements in this trend is the recognition of the dualistic model that categorizes various types of ovarian cancer into two groups designated high-grade (HG) and low-grade (LG) tumors. However, the tumor genome sequencing data suggest the existence of 6 ovarian carcinoma subtypes, including two LG and four HG subtypes. Subtype C1 exhibits a high stromal response and the lowest survival. Subtypes C2 and C4 demonstrate higher number of intratumoral CD3 + cells, lower stromal gene expression and better survival than sybtype C1. Subtype C5 (mesenchymal) is characterized by mesenchymal cells, over-expression of N-cadherin and P-cadherin, low expression of differentiation markers, and lower survival rates than C2 and C4. The use of a consensus algorithm to determine the subtype allows identification of only a minority of ovarian carcinomas (approximately 25%) therefore, the practical importance of this classification requires additional research. There is evidence that it makes sense to randomize tumors into groups with altered expression of angiogenic genes and groups with overexpression of the immune response genes, as in the angiogenic group there is a comparative superiority in terms of survival. The administration of bevacizumab in the angiogenic group improves survival, while the administration of bevacizumab in the immune group even worsens the outcome. Molecular subtypes with worse survival rates (proliferative and mesenchymal) also benefit most from bevacizumab treatment. This review focuses on some of the advances in understanding molecular, cellular, and genetic changes in ovarian carcinomas with the results achieved so far regarding the formulation of molecular subtypes of ovarian cancer, however further studies are needed.

scholarly journals Deletion at 6q24.2-26 predicts longer survival of high-grade serous epithelial ovarian cancer patients

2014 ◽  
Vol 9 (2) ◽  
pp. 422-436 ◽  
Author(s):  
Marta M. Kamieniak ◽  
Daniel Rico ◽  
Roger L. Milne ◽  
Ivan Muñoz-Repeto ◽  
Kristina Ibáñez ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cancer Patients ◽  
High Grade ◽  
Serous Epithelial Ovarian Cancer

scholarly journals Differential expression of SLIT and NTRK-like family member 3 in human epithelial ovarian cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Family Member ◽  
Fallopian Tube ◽  
Expression Profiles ◽  
Gynecologic Cancer ◽  
Progression Free Survival ◽  
High Grade ◽  
Primary Tumors ◽  
Ovarian Cancers

Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer (1). We performed discovery of genes associated with epithelial ovarian cancer and of the high-grade serous ovarian cancer (HGSC) subtype, using published and public microarray data (2, 3) to compare global gene expression profiles of normal ovary or fallopian tube with that of primary tumors from women diagnosed with epithelial ovarian cancer or HGSC. We identified the gene encoding SLIT and NTRK-like family member 3, SLITRK3, as among the genes whose expression was most different in epithelial ovarian cancer as compared to the normal fallopian tube. SLITRK3 expression was significantly lower in high-grade serous ovarian tumors relative to normal fallopian tube. SLITRK3 expression correlated with progression-free survival in patients with ovarian cancer. These data indicate that expression of SLITRK3 is perturbed in epithelial ovarian cancers broadly and in ovarian cancers of the HGSC subtype. SLITRK3 may be relevant to pathways underlying ovarian cancer initiation (transformation) or progression.

scholarly journals Differential expression of LSM4 homolog, U6 small nuclear RNA and mRNA degradation associated in human epithelial ovarian cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Fallopian Tube ◽  
Expression Profiles ◽  
Mrna Degradation ◽  
High Grade ◽  
Small Nuclear Rna ◽  
Primary Tumors ◽  
Ovarian Cancers ◽  
Nuclear Rna

Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer (1). We performed discovery of genes associated with epithelial ovarian cancer and of the high-grade serous ovarian cancer (HGSC) subtype, using published microarray data (2, 3) to compare global gene expression profiles of normal ovary or fallopian tube with that of primary tumors from women diagnosed with epithelial ovarian cancer or HGSC. We identified the gene encoding LSM4 homolog, U6 small nuclear RNA and mRNA degradation associated, LSM4, as among the genes whose expression was most different in epithelial ovarian cancer as compared to the normal fallopian tube. LSM4 expression was significantly higher in high-grade serous ovarian tumors relative to normal fallopian tube. LSM4 expression correlated with overall survival in patients with ovarian cancer. These data indicate that expression of LSM4 is perturbed in epithelial ovarian cancers broadly and in ovarian cancers of the HGSC subtype. LSM4 may be relevant to pathways underlying ovarian cancer initiation (transformation) or progression.

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