Dataset Information

A combination of molecular and clinical parameters provides a new strategy for high-grade serous ovarian cancer patient management

ABSTRACT: High-grade serous carcinoma (HGSC) is the most common and deadly subtype of ovarian cancer. Although most patients will initially respond to first-line treatment with a combination of surgery and platinum-based chemotherapy, up to a quarter will be resistant to treatment. We aimed to identify a new strategy to improve HGSC patient management at the time of cancer diagnosis (HGSC-1LTR). Using proteomics in ready-available HGSC tissues, we have identified a molecular signature (TKT, LAMC1 and FUCO) that combined with ready available clinical data is able to predict patient response to first-line treatment (AUC: 0.82). Identification of chemoresistance at the time of diagnosis can facilitate the study of alternative treatments aimed at improving patient outcome. In addition, those patients classified as chemosensitive could undergo standard care with platinum-based agents. Therefore, the HGSC-1LTR strategy can allow optimization of therapeutic decision making and individualize HGSC patients’ care

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Ovary

DISEASE(S): Malignant Neoplasm Of Ovary

SUBMITTER: Eva Borràs

LAB HEAD: Eduard Sabido

PROVIDER: PXD035084 | Pride | 2023-03-11

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	180221_MLAS_21samples.pdResult	Other
	180221_S_MLAS_02_01_less_6m.raw	Raw
	180221_S_MLAS_05_01_less_6m.raw	Raw
	180221_S_MLAS_10_01_less_6m.raw	Raw
	180221_S_MLAS_11_01_more_6m.raw	Raw

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A combination of molecular and clinical parameters provides a new strategy for high-grade serous ovarian cancer patient management.

Bradbury Melissa M Borràs Eva E Vilar Marta M Castellví Josep J Sánchez-Iglesias José Luis JL Pérez-Benavente Assumpció A Gil-Moreno Antonio A Santamaria Anna A Sabidó Eduard E

Journal of translational medicine 20221221 1

<h4>Background</h4>High-grade serous carcinoma (HGSC) is the most common and deadly subtype of ovarian cancer. Although most patients will initially respond to first-line treatment with a combination of surgery and platinum-based chemotherapy, up to a quarter will be resistant to treatment. We aimed to identify a new strategy to improve HGSC patient management at the time of cancer diagnosis (HGSC-1LTR).<h4>Methods</h4>A total of 109 ready-available formalin-fixed paraffin-embedded HGSC tissues ...[more]

PMID: 36544142

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Project description:Ovarian cancer (OC) ranks among the deadliest cancers in women. Lack of symptoms, rapid spread of metastases and common chemoresistance contribute to unfortunate fate of majority of OC patients, especially those having high-grade serous carcinoma of the ovary, fallopian tube and peritoneum (HGSC), the most common type of OC. Many HGSC patients have excess fluid in the peritoneum at the stage of diagnosis called ascites. Ascites is basically a tumor microenvironment (TME) in the liquid form containing various cells, proteins and also extracellular vesicles (EVs). EVs are small membrane-bound particles that convey proteins, lipids and nucleic acids between cells and their cargo reflects the cell of origin. EVs play important role in cancerogenesis and hold great promise as disease biomarkers as well as potential therapeutic targets. Small size and polydispersity of EVs bring various challenges to their isolation and characterization, including method-dependent enrichment of different EV subtypes as well as contaminants. We isolated EVs from ascites of 11 patients by two different methods (ultracentrifugation coupled to sucrose cushion and size-exclusion chromatography, qEV column) and analyzed them by mass spectrometry. We identified core ascitic EV proteins present in all patients that contain typical EV markers and are devoid of method-dependent contaminants. To cover interpatient heterogeneity, we expanded this “core proteome” with proteins found in majority of patients. Next, we compared them with proteins of EVs from related control fluids and uncovered proteins present only on EVs from HGSC patients. We believe this list of proteins contain both important players of HGSC progression as well as potential biomarkers. Using single cell RNA sequencing data, we mapped the origin of EVs to different types of cells present in malignant ascites. Our results suggest that EVs in ascites do not come predominantly from tumor cells, but rather from variety of non-malignant cell types including cancer-associated fibroblasts and tumor-associated macrophages, which presence in ascites was confirmed by flow cytometry. This emphasizes the recently appreciated role of TME in the progression of HGSC. To conclude, this is the first study attempting to link EV composition to the cell types producing it. As such it opens numerous avenues both for better understanding of EV role in tumor promotion/prevention and for the improved HGSC diagnostics.