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Identifying the Signatures and Rules of Circulating Extracellular MicroRNA for Distinguishing Cancer Subtypes.

ABSTRACT: Cancer is one of the most threatening diseases to humans. It can invade multiple significant organs, including lung, liver, stomach, pancreas, and even brain. The identification of cancer biomarkers is one of the most significant components of cancer studies as the foundation of clinical cancer diagnosis and related drug development. During the large-scale screening for cancer prevention and early diagnosis, obtaining cancer-related tissues is impossible. Thus, the identification of cancer-associated circulating biomarkers from liquid biopsy targeting has been proposed and has become the most important direction for research on clinical cancer diagnosis. Here, we analyzed pan-cancer extracellular microRNA profiles by using multiple machine-learning models. The extracellular microRNA profiles on 11 cancer types and non-cancer were first analyzed by Boruta to extract important microRNAs. Selected microRNAs were then evaluated by the Max-Relevance and Min-Redundancy feature selection method, resulting in a feature list, which were fed into the incremental feature selection method to identify candidate circulating extracellular microRNA for cancer recognition and classification. A series of quantitative classification rules was also established for such cancer classification, thereby providing a solid research foundation for further biomarker exploration and functional analyses of tumorigenesis at the level of circulating extracellular microRNA.

SUBMITTER: Yuan F

PROVIDER: S-EPMC7985347 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Purpose: There is a quest for novel non-invasive diagnostic markers for the detection of breast cancer. The goal of this study is to identify circulating microRNA signatures using a cohort of Asian Chinese breast cancer patients, and to compare microRNA profiles between tumour and serum samples. Experimental design: MicroRNAs from paired breast cancer tumours, normal tissue and serum samples derived from 32 patients were comprehensively profiled using microarrays (1300 microRNAs against tumour and normal tissues) or LNA RT-PCR panels (742 microRNAs against serum samples). Serum samples from healthy individuals (n=22) were also employed as normal controls. Significant serum microRNAs, identified by logistic regression, were validated in an independent set of serum samples from patients (n=82) and healthy controls (n=53). Results: The 20 most significant microRNAs differentially expressed in breast cancer tumours included miR-21, miR-10b, and miR-145, previously shown to be dysregulated in breast cancer. Interestingly, 16 of the 20 most significant microRNAs differentially expressed in serum samples were novel. MiR-1, miR-92a, miR-133a and miR-133b were identified as the most important diagnostic markers, and were successfully validated; receiver operating characteristic curves derived from combinations of these microRNAs exhibited areas under the curves of 0.944-0.946. Only seven microRNAs were overexpressed in both tumours and serum, suggesting that microRNAs may be released into the serum selectively. Conclusion: The clinical employment of microRNA signatures as a non-invasive diagnostic strategy is promising, but should be further validated for different subtypes of breast cancers. Blood samples were collected in Becton Dickinson (Franklin Lakes, NJ) Vacutainer SST tubes. Serum was harvested by centrifugation at 2200g after allowing blood to clot for 30mins. 32 patient samples and 22 samples from healthy controls were obtained for profiling. Sera samples were stored at -80oC.

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Identifying the Signatures and Rules of Circulating Extracellular MicroRNA for Distinguishing Cancer Subtypes.

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