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000267558 1001_ $$00000-0003-3644-743X$$aOtto, Raik$$b0
000267558 245__ $$aTranscriptomic Deconvolution of Neuroendocrine Neoplasms Predicts Clinically Relevant Characteristics.
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000267558 520__ $$aPancreatic neuroendocrine neoplasms (panNENs) are a rare yet diverse type of neoplasia whose precise clinical-pathological classification is frequently challenging. Since incorrect classifications can affect treatment decisions, additional tools which support the diagnosis, such as machine learning (ML) techniques, are critically needed but generally unavailable due to the scarcity of suitable ML training data for rare panNENs. Here, we demonstrate that a multi-step ML framework predicts clinically relevant panNEN characteristics while being exclusively trained on widely available data of a healthy origin. The approach classifies panNENs by deconvolving their transcriptomes into cell type proportions based on shared gene expression profiles with healthy pancreatic cell types. The deconvolution results were found to provide a prognostic value with respect to the prediction of the overall patient survival time, neoplastic grading, and carcinoma versus tumor subclassification. The performance with which a proliferation rate agnostic deconvolution ML model could predict the clinical characteristics was found to be comparable to that of a comparative baseline model trained on the proliferation rate-informed MKI67 levels. The approach is novel in that it complements established proliferation rate-oriented classification schemes whose results can be reproduced and further refined by differentiating between identically graded subgroups. By including non-endocrine cell types, the deconvolution approach furthermore provides an in silico quantification of panNEN dedifferentiation, optimizing it for challenging clinical classification tasks in more aggressive panNEN subtypes.
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000267558 650_7 $$2Other$$aNEN classification
000267558 650_7 $$2Other$$adeconvolution
000267558 650_7 $$2Other$$amachine learning
000267558 650_7 $$2Other$$aneuroendocrine carcinoma
000267558 650_7 $$2Other$$aneuroendocrine neoplasm
000267558 650_7 $$2Other$$aneuroendocrine tumor
000267558 7001_ $$aDetjen, Katharina M$$b1
000267558 7001_ $$0P:(DE-He78)f881225f7918c1443b368473d303998b$$aRiemer, Pamela$$b2
000267558 7001_ $$00000-0003-2282-2585$$aFattohi, Melanie$$b3
000267558 7001_ $$00000-0001-9872-3087$$aGrötzinger, Carsten$$b4
000267558 7001_ $$00000-0003-2996-4404$$aRindi, Guido$$b5
000267558 7001_ $$aWiedenmann, Bertram$$b6
000267558 7001_ $$aSers, Christine$$b7
000267558 7001_ $$aLeser, Ulf$$b8
000267558 773__ $$0PERI:(DE-600)2527080-1$$a10.3390/cancers15030936$$gVol. 15, no. 3, p. 936 -$$n3$$p936$$tCancers$$v15$$x2072-6694$$y2023
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