AUTHOR=Liu Haiyan , Qiu Chun , Wang Bo , Bing Pingping , Tian Geng , Zhang Xueliang , Ma Jun , He Bingsheng , Yang Jialiang TITLE=Evaluating DNA Methylation, Gene Expression, Somatic Mutation, and Their Combinations in Inferring Tumor Tissue-of-Origin JOURNAL=Frontiers in Cell and Developmental Biology VOLUME=9 YEAR=2021 URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.619330 DOI=10.3389/fcell.2021.619330 ISSN=2296-634X ABSTRACT=
Carcinoma of unknown primary (CUP) is a type of metastatic cancer, the primary tumor site of which cannot be identified. CUP occupies approximately 5% of cancer incidences in the United States with usually unfavorable prognosis, making it a big threat to public health. Traditional methods to identify the tissue-of-origin (TOO) of CUP like immunohistochemistry can only deal with around 20% CUP patients. In recent years, more and more studies suggest that it is promising to solve the problem by integrating machine learning techniques with big biomedical data involving multiple types of biomarkers including epigenetic, genetic, and gene expression profiles, such as DNA methylation. Different biomarkers play different roles in cancer research; for example, genomic mutations in a patient’s tumor could lead to specific anticancer drugs for treatment; DNA methylation and copy number variation could reveal tumor tissue of origin and molecular classification. However, there is no systematic comparison on which biomarker is better at identifying the cancer type and site of origin. In addition, it might also be possible to further improve the inference accuracy by integrating multiple types of biomarkers. In this study, we used primary tumor data rather than metastatic tumor data. Although the use of primary tumors may lead to some biases in our classification model, their tumor-of-origins are known. In addition, previous studies have suggested that the CUP prediction model built from primary tumors could efficiently predict TOO of metastatic cancers (