Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: Molecular diagnosis and prognosis of cancers of unknown-primary (CUPs): progress from a microRNA-based droplet digital PCR assay Metastasis is responsible for the majority of cancer-related deaths. Particularly challenging is the management of metastatic cancer of unknown primary site (CUP), whose tissue-of-origin (TOO) remains undetermined even after expensive investigations. CUP therapy is rather unspecific and poorly effective. Molecular approaches developed to identify CUPs potential tissue-of-origin, can overcome some of these issues. In this study, we applied a pre-determined set of microRNAs (miRNAs) to infer the TOO of 53 metastatic cancers of unknown or uncertain origin. We designed a molecular assay to quantify 89 miRNAs at the copy number level, using EvaGreen-based Droplet Digital PCR. We assessed miRNA expression in 159 samples including primary tumors from 17 tumor classes (reference set), metastases of known and unknown origin. We applied two different statistical models for class prediction to obtain CUPs most probable TOOs. Specifically, we used the shrunken centroids using PAMR (Prediction Analysis of Microarrays for R) and the least absolute shrinkage and selection operator (LASSO) models. The molecular test was successfully applied to FFPE samples and provided a site-of-origin identification within one-week from the biopsy procedure. The most frequently predicted origins were gastrointestinal, pancreas, breast and lung. The assay was applied to multiple metastases from the same CUP, collected from different metastatic sites: the molecular prediction revealed an impressive agreement in site-of-origin prediction, intrinsically validating our assay. The final prediction was compared with the clinico-pathological hypothesis of primary site. Moreover, a panel of 14 miRNAs proved to have prognostic value and being associated with overall survival. Our study demonstrated that miRNA expression profiling in CUP samples could be employed as diagnostic and prognostic test. Our molecular analysis can be performed on-request, concomitantly with standard diagnostic workup and in association with genetic profiling, to offer valuable indication about the possible primary site, thereby supporting treatment decisions.
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The categories of this paper are: education
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The categories of this paper are: pharmacology
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The categories of this paper are: biophysics
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The categories of this paper are: and
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The categories of this paper are: genomics
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The categories of this paper are: behavior
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The categories of this paper are: synthetic
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The categories of this paper are: biochemistry
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The categories of this paper are: developmental
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The categories of this paper are: biology
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The categories of this paper are: molecular
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The categories of this paper are: toxicology
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The categories of this paper are: cognition
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The categories of this paper are: cancer
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The categories of this paper are: animal
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The categories of this paper are: epidemiology