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Proteomic profiling to predict therapeutic response to anti-PD1 therapy in advanced melanoma – Orbitrap Elite dataset depleted serum

ABSTRACT: MS-based proteomics based on data-dependent acquisition / shotgun MS was used to study the response of melanoma patients to anti-PD1 therapy. Human serum samples were collected from patients at the start of their therapy and later categorized into responders and non-responders based on clinical outcome. Samples were subjected to immunodepletion and proteins were identified by bottom-up proteomics.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Serum

DISEASE(S): Melanoma

SUBMITTER: Alexander Leitner

LAB HEAD: Ruedi Aebersold

PROVIDER: PXD027849 | Pride | 2023-08-18

REPOSITORIES: Pride

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Project description:Dilated cardiomyopathy (DCM) is a disease of the heart muscle characterized by left ventricular or biventricular dilation and systolic dysfunction. It presents one of the most common causes of heart failure worldwide and also the most common indication for heart transplantation. Despite the discharge treatment possibilities, the outcome of patients with recent onset DCM often remains unpredictable and major adverse events may occur in the first months following the diagnosis. Enhancement in the left ventricular ejection fraction – designed as the left ventricular reverse remodeling (LVRR) – has been considered one of the most important determinants of the improvement and treatment response in the prognosis of DCM. In the present study we performed a comprehensive quantitative proteomic analysis of DCM patients’ plasma samples. First we searched for the differences against healthy control group and found several proteins and biological processes to be significantly regulated. The most DCM up-regulated terms corresponded to inflammatory response, wound healing and complement. Among the most relevant DCM up-regulated proteins were CRP, CD163, AOC3, PF4, IGF2, IGFBP2 and TNC. Down-regulation in DCM samples was observed in the biological processes of blood coagulation and lipid metabolism, both of which present risk factors in cardiovascular diseases. The most relevant down-regulated proteins in DCM were TTN, GSN, FCN3, PON1, PON3, and COMP. In the second part of the study, we observed the clinical fate of the DCM patients one year after admission. We divided them according to their treatment response into subgroups of responders (LVRR+) and non-responders (LVRR-) and searched for proteins that would help to predict the patient’s fate or to elucidate the molecular consequences of the disease progression. The protein with the best prognostic potential was ALDOB, its elevated plasma level was found in patients with worse or fatal outcome. The patients with no or poor treatment response had also up-regulated immunoglobulins and pathways corresponding to immunoglobulin-mediated immune response together with cell adhesion which points to the importance of these processes in the DCM pathology.

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	nzila_C1710_068.raw	Raw

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Proteomic profiling to predict therapeutic response to anti-PD1 therapy in advanced melanoma – Orbitrap Elite dataset depleted serum

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