RNA-Seq Accurately Identifies Cancer Biomarker Signatures to Distinguish Tissue of Origin

Iris H. Wei, Yang Shi, Hui Jiang, Chandan Kumar-Sinha, Arul M. Chinnaiyan

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Metastatic cancer of unknown primary (CUP) accounts for up to 5% of all new cancer cases, with a 5-year survival rate of only 10%. Accurate identification of tissue of origin would allow for directed, personalized therapies to improve clinical outcomes. Our objective was to use transcriptome sequencing (RNA-Seq) to identify lineage-specific biomarker signatures for the cancer types that most commonly metastasize as CUP (colorectum, kidney, liver, lung, ovary, pancreas, prostate, and stomach). RNA-Seq data of 17,471 transcripts from a total of 3,244 cancer samples across 26 different tissue types were compiled from in-house sequencing data and publically available International Cancer Genome Consortium and The Cancer Genome Atlas datasets. Robust cancer biomarker signatures were extracted using a 10-fold cross-validation method of log transformation, quantile normalization, transcript ranking by area under the receiver operating characteristic curve, and stepwise logistic regression. The entire algorithm was then repeated with a new set of randomly generated training and test sets, yielding highly concordant biomarker signatures. External validation of the cancer-specific signatures yielded high sensitivity (92.0% ± 3.15%; mean ± standard deviation) and specificity (97.7% ± 2.99%) for each cancer biomarker signature. The overall performance of this RNA-Seq biomarker-generating algorithm yielded an accuracy of 90.5%. In conclusion, we demonstrate a computational model for producing highly sensitive and specific cancer biomarker signatures from RNA-Seq data, generating signatures for the top eight cancer types responsible for CUP to accurately identify tumor origin.

Original languageEnglish (US)
Pages (from-to)918-927
Number of pages10
JournalNeoplasia
Volume16
Issue number11
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research
  • Medicine(all)

Fingerprint Dive into the research topics of 'RNA-Seq Accurately Identifies Cancer Biomarker Signatures to Distinguish Tissue of Origin'. Together they form a unique fingerprint.

  • Cite this