Identification of potential tissue-specific cancer biomarkers and development of cancer versus normal genomic classifiers

Authors

Akram Mohammed, University of Nebraska-LincolnFollow
Greyson Biegert, University of Nebraska-Lincoln
Jiri Adamec, University of Nebraska-LincolnFollow
Tomáš Helikar, University of Nebraska-LincolnFollow

Document Type

Article

Date of this Version

9-21-2017

Citation

Oncotarget, 2017, Vol. 8, (No. 49), pp: 85692-85715

doi: 10.18632/oncotarget.21127

Comments

Copyright: Mohammed et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0

Abstract

Machine learning techniques for cancer prediction and biomarker discovery can hasten cancer detection and significantly improve prognosis. Recent “OMICS” studies which include a variety of cancer and normal tissue samples along with machine learning approaches have the potential to further accelerate such discovery. To demonstrate this potential, 2,175 gene expression samples from nine tissue types were obtained to identify gene sets whose expression is characteristic of each cancer class. Using random forests classification and ten-fold cross-validation, we developed nine single-tissue classifiers, two multi-tissue cancer-versus-normal classifiers, and one multi-tissue normal classifier. Given a sample of a specified tissue type, the single-tissue models classified samples as cancer or normal with a testing accuracy between 85.29% and 100%. Given a sample of non-specific tissue type, the multitissue bi-class model classified the sample as cancer versus normal with a testing accuracy of 97.89%. Given a sample of non-specific tissue type, the multi-tissue multiclass model classified the sample as cancer versus normal and as a specific tissue type with a testing accuracy of 97.43%. Given a normal sample of any of the nine tissue types, the multi-tissue normal model classified the sample as a particular tissue type with a testing accuracy of 97.35%. The machine learning classifiers developed in this study identify potential cancer biomarkers with sensitivity and specificity that exceed those of existing biomarkers and pointed to pathways that are critical to tissuespecific tumor development. This study demonstrates the feasibility of predicting the tissue origin of carcinoma in the context of multiple cancer classes.