Efficient Identification of miRNAs for Classification of Tumor Origin

Abstract

Carcinomas of unknown primary origin constitute 3% to 5% of all newly diagnosed metastatic cancers, with the primary source difficult to classify with current histological methods. Effective cancer treatment depends on early and accurate identification of the tumor; patients with metastases of unknown origin have poor prognosis and short survival. Because miRNA expression is highly tissue specific, the miRNA profile of a metastasis may be used to identify its origin. We therefore evaluated the potential of miRNA profiling to identify the primary tumor of known metastases. Two hundred eight formalin-fixed, paraffin-embedded samples, representing 15 different histologies, were profiled on a locked nucleic acideenhanced microarray platform, which allows for highly sensitive and specific detection of miRNA.On the basis of these data, we developed and cross-validated a novel classification algorithm, least absolute shrinkage and selection operator, which had an overall accuracy of 85% (CI, 79%e89%). When the classifier was applied on an independent test set of 48 metastases, the primary site was correctly identified in 42 cases (88% accuracy; CI, 75%e94%). Our findings suggest that miRNA expression profiling on paraffin tissue can efficiently predict the primary origin of a tumor and may provide pathologists with a molecular diagnostic tool that can improve their capability to correctly identify the origin of hitherto unidentifiable metastatic tumors and, eventually, enable tailored therapy.

miRNAs as novel biomarkers in the management of prostate cancer

“…The highly tissue specific origin of miRNAs leads to an efficient identification of metastatic cancers of unknown primary origin. Søkilde et al [23] reported in a series of 208 tumors, representing 15 different histologies including PCa, that miRNA expression profiling on paraffin tissue can efficiently predict the primary origin of the tumor. The authors developed a new miRNAs classification algorithm, obtaining an overall accuracy of 85% (CI: 79%-89%).…”

miR-1247-5p functions as a tumor suppressor in human hepatocellular carcinoma by targeting Wnt3

“…However, the molecular mechanisms involved in the initiation and progression of HCC are still poorly understood. Recently, the role of epigenetic regulation, particularly DNA methylation and the aberrant expression of miRNAs, in the occurrence and development of cancers is gradually being recognized (2,3).…”

Comparative analysis of microRNA profiles between adult Ascaris lumbricoides and Ascaris suum

“…Due to their specific expression in different organisms, tissues and cells, miRNAs may provide potential novel biomarkers [27-29]. Our previous study indicated that different T. gondii genotypes have their unique miRNA profiles [30].…”

“…miRNAs are also important for pathogen-host interactions [23-26]. Recently studies have indicated that miRNAs may represent potential biomarkers for various biomedical problems, such as the differentiation of different tumors and muscular tissues [27-29], and they may provide biomarkers for the characterization of different genotypes of Toxoplasma gondii [30]. …”