scholarly journals Unraveling endometriosis-associated ovarian carcinomas using integrative proteomics

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 189
Author(s):  
Felix Leung ◽  
Marcus Q. Bernardini ◽  
Kun Liang ◽  
Ihor Batruch ◽  
Marjan Rouzbahman ◽  
...  

Background: To elucidate potential markers of endometriosis and endometriosis-associated endometrioid and clear cell ovarian carcinomas using mass spectrometry-based proteomics. Methods: A total of 21 fresh, frozen tissues from patients diagnosed with clear cell carcinoma, endometrioid carcinoma, endometriosis and benign endometrium were subjected to an in-depth liquid chromatography-tandem mass spectrometry analysis on the Q-Exactive Plus. Protein identification and quantification were performed using MaxQuant, while downstream analyses were performed using Perseus and various bioinformatics databases. Results: Approximately 9000 proteins were identified in total, representing the first in-depth proteomic investigation of endometriosis and its associated cancers. This proteomic data was shown to be biologically sound, with minimal variation within patient cohorts and recapitulation of known markers. While moderate concordance with genomic data was observed, it was shown that such data are limited in their abilities to represent tumours on the protein level and to distinguish tumours from their benign precursors. Conclusions: The proteomic data suggests that distinct markers may differentiate endometrioid and clear cell carcinoma from endometriosis. These markers may be indicators of pathobiology but will need to be further investigated. Ultimately, this dataset may serve as a basis to unravel the underlying biology of the endometrioid and clear cell cancers with respect to their endometriotic origins.

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 189
Author(s):  
Felix Leung ◽  
Marcus Q. Bernardini ◽  
Kun Liang ◽  
Ihor Batruch ◽  
Marjan Rouzbahman ◽  
...  

Background: To elucidate potential markers of endometriosis and endometriosis-associated endometrioid and clear cell ovarian carcinomas using mass spectrometry-based proteomics. Methods: A total of 21 fresh, frozen tissues from patients diagnosed with clear cell carcinoma, endometrioid carcinoma, endometriosis and benign endometrium were subjected to an in-depth liquid chromatography-tandem mass spectrometry analysis on the Q-Exactive Plus. Protein identification and quantification were performed using MaxQuant, while downstream analyses were performed using Perseus and various bioinformatics databases. Results: Approximately 9000 proteins were identified in total, representing the first in-depth proteomic investigation of endometriosis and its associated cancers. This proteomic data was shown to be biologically sound, with minimal variation within patient cohorts and recapitulation of known markers. While moderate concordance with genomic data was observed, it was shown that such data are limited in their abilities to represent tumours on the protein level and to distinguish tumours from their benign precursors. Conclusions: The proteomic data suggests that distinct markers may differentiate endometrioid and clear cell carcinoma from endometriosis. These markers may be indicators of pathobiology but will need to be further investigated. Ultimately, this dataset may serve as a basis to unravel the underlying biology of the endometrioid and clear cell cancers with respect to their endometriotic origins.


2019 ◽  
Vol 24 (10) ◽  
pp. 1273-1283 ◽  
Author(s):  
Kazuki Takasaki ◽  
Morikazu Miyamoto ◽  
Masashi Takano ◽  
Hiroaki Soyama ◽  
Tadashi Aoyama ◽  
...  

2021 ◽  
Author(s):  
Yassel Ramos ◽  
Alexis Almeida ◽  
Jenis Carpio ◽  
Arielis Rodríguez-Ulloa ◽  
Yasser Perera ◽  
...  

AbstractSample preparation and protein fractionation are important issues in proteomic studies in spite of the technological achievements on protein mass spectrometry. Protein extraction procedures strongly affect the performance of fractionation methods by provoking protein dispersion in several fractions. The most notable exception is SDS-PAGE-based protein fractionation due to its extraordinary resolution and the effectiveness of SDS as a solubilizing agent. Its main limitation lies in the poor recovery of the gel-trapped proteins, where protein electro-elution is the most successful approach to overcome this drawback. We created a device to separate complex mixture of proteins and peptides (named “GEES fractionator”) that is based on the continuous Gel Electrophoresis/Electro-elution Sorting of these molecules. In an unsupervised process, complex mixtures of proteins or peptides are fractionated into the gel while separated fractions are simultaneously and sequentially electro-eluted to the solution containing wells. The performance of the device was studied for SDS-PAGE-based protein fractionation in terms of reproducibility, protein recovery and loading capacity. In the SDS-free PAGE setup, complex peptide mixtures can also be fractionated. More than 11 700 proteins were identified in the whole-cell lysate of the CaSki cell line by using the GEES fractionator combined with the Filter Aided Sample Preparation (FASP) method and mass spectrometry analysis. GEES-based proteome characterization shows a 1.7 fold increase in the number of identified proteins compared to the unfractionated sample analysis. Proteins involved in the co-regulated transcription activity, as well as cancer related pathways such as apoptosis signaling, P53 and RAS pathways are more represented in the protein identification output of GEES-based fractionation approaches.


2021 ◽  
Author(s):  
Sartaj Ahmad Mir ◽  
Soon Boon Justin Wong ◽  
Kothandaraman Narasimhan ◽  
Chua Wee Ling Esther ◽  
Shanshan Ji ◽  
...  

Abstract Cancer metabolism is associated with enhanced lipogenesis required for rapid growth and proliferation. However, the magnitude of dysregulation of diverse lipid species mostly remains to be characterized, particularly in rare cancers such as ovarian clear cell carcinoma (OCCC). Here we implemented a robust sample preparation workflow together with targeted LC-MS/MS to identify the lipidomic changes in formalin-fixed paraffin-embedded specimen from OCCC as compared to uninvolved contralateral ovarian tissue. We quantitated 342 lipid species representing 28 lipid classes. We observed differential regulation of diverse lipid species belonging to several glycerophospholipid classes and trihexosylceramide. A number of unsaturated lipid species were increased whereas saturated lipid showed a decrease in OCCC as compared to the controls. We also carried out total fatty acid analysis and observed increase in the levels of several unsaturated fatty acids with concomitant increase in the index of stearoyl-CoA desaturase (SCD) in OCCC. We confirmed the upregulation of SCD, the rate-limiting enzyme for the synthesis of monounsaturated fatty acids, by immunohistochemistry (IHC) assays. Hence, by carrying out mass spectrometry analysis of archival tissue samples, we were able to provide novel insights into the lipidomic alterations of OCCC.


2003 ◽  
Vol 30 (5) ◽  
pp. 471 ◽  
Author(s):  
Joshua L. Heazlewood ◽  
A. Harvey Millar

Protein analysis has been at the heart of plant science for many years, but with new questions emerging from an abundance of genomic information and further improvements in technology, there are now new opportunities to undertake large-scale analyses and to move to more complex systems than has been possible previously. This explosion of interest and data is often referred to simply as proteomics, which is the study of the complete set of proteins expressed at a given time and place, the proteome. As its name suggests proteomics is intricately linked to allied technologies such as genomics, transcriptomics and metabolomics. In this review of plant proteomics we outline a series of issues that face the practical user, particularly the largest problem that currently faces researchers, the myriad of options to choose from. The choices, problems and pitfalls of entering into gel-based and non-gel-based arraying techniques are discussed together with advances in pre-fractionation of samples, liquid chromatography separations and subcellular analyses. Issues relating to mass spectrometry analysis and the eventual protein identification are outlined, and the dilemmas of data storage and analysis are highlighted. During this tour we provide a series of references to the literature — experimental, theoretical and technical — to illustrate the breadth of current investigations using these techniques.


2021 ◽  
Vol 5 (2) ◽  
pp. 267-275
Author(s):  
Muthia Kamelia ◽  
Aswiyanti Asri ◽  
Syamel Muhammad

Objective: To report the case of ovarian clear cell carcinoma with involvement of both ovaries and metastatic to ascitic fluid and the label mass in the bladderMethod: Case Report  Case: A 51 years old female presented with enlarging abdominal with gradual pain. The result of transabdominal sonography were multiple cysts with solid mass, suspected solid cystic ovarian neoplasm and ascites. The patient prepared for laparotomy; optimal debulking surgery, mass resection from bladder. Cytology examination was performed from ascitic fluid and it was confirmed by histopathology examination.Result: Microscopic features on cytology examination of ascitic fluid smear was suggest carcinoma. Histological examination was confirmed the diagnosis and the result was ovarian clear cell carcinoma. Discussion: Ovarian clear cell carcinoma is a rare subtype of epithelial ovarian cancer and comprises about 5-10% of ovarian carcinomas. Clear cell carcinoma tends to occur in the fifth to seventh decades. Cytology examination showed the cellular smear consists of groups of epithelial cells with large nucleus, hyperchromatic, pale-staining, vacuolated cytoplasm. There is also eosinophilic, extracellular substance. The presence of a tumor in ascitic fluid and the label mass in the bladder can categorize become IIB. This determined based on the FIGO’s ovarian tumor staging system.Keywords: ovarian clear cell carcinoma; ascitic fluid.


2009 ◽  
Vol 19 (3) ◽  
pp. 471-479 ◽  
Author(s):  
Hiroshi Kobayashi ◽  
Yoshihiko Yamada ◽  
Seiji Kanayama ◽  
Naoto Furukawa ◽  
Taketoshi Noguchi ◽  
...  

Problem:Clear cell carcinoma (CCC) of the ovary has a number of features distinguishing it from other epithelial ovarian carcinomas (EOC) because of its characteristic histology and biology, frequent concurrence with endometriotic lesion, and highly chemoresistant nature resulting in an extremely poor prognosis. The incidence of CCC has been steadily increasing in Japan. They comprise approximately 20% of all EOC. Understanding the mechanisms of CCC development and elucidating pathogenesis and pathophysiology are intrinsic to prevention and effective therapies for CCC.Method of study:This article reviews the English language literature for biology, pathogenesis, and pathophysiological studies on endometriosis-associated EOC. Several data are discussed in the context of endometriosis and CCC biology.Results:Recent studies based on genome-wide expression analysis technology have noted specific expression of hepatocyte nuclear factor-1β (HNF-1β) in endometriosis and CCC, suggesting that early differentiation into the clear cell lineage takes place in the endometriosis. The HNF-1β-dependent pathway of CCC will be discussed, which are providing new insights into regulation of apoptosis and glycogen synthesis and resistance of CCC to anticancer agents.Conclusions:This review summarizes recent advances in the HNF-1β and its target genes; the potential challenges to the understanding of carcinogenesis, pathogenesis, and pathophysiology of CCC; and a possible novel model is proposed.


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