Comprehensive and Computable Molecular Diagnostic Panel (C2Dx) From Small Volume Specimens for Precision Oncology: Molecular Subtyping of Non-Small Cell Lung Cancer From Fine Needle Aspirates

Jing Su; Lynn S Huang; Ryan Barnard; Graham Parks; James Cappellari; Christina Bellinger; Travis Dotson; Lou Craddock; Bharat Prakash; Jonathan Hovda; Hollins Clark; William Jeffrey Petty; Boris Pasche; Michael D Chan; Lance D Miller; Jimmy Ruiz

doi:10.3389/fonc.2021.584896

Comprehensive and Computable Molecular Diagnostic Panel (C2Dx) From Small Volume Specimens for Precision Oncology: Molecular Subtyping of Non-Small Cell Lung Cancer From Fine Needle Aspirates

Front Oncol. 2021 Apr 16:11:584896. doi: 10.3389/fonc.2021.584896. eCollection 2021.

Authors

Jing Su^{1

2

3}, Lynn S Huang³, Ryan Barnard³, Graham Parks⁴, James Cappellari⁴, Christina Bellinger⁵, Travis Dotson⁵, Lou Craddock¹, Bharat Prakash⁵, Jonathan Hovda⁶, Hollins Clark⁷, William Jeffrey Petty⁸, Boris Pasche¹, Michael D Chan⁶, Lance D Miller¹, Jimmy Ruiz^{8

9}

Affiliations

¹ Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC, United States.
² Department of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, IN, United States.
³ Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, NC, United States.
⁴ Department of Pathology, Wake Forest School of Medicine, Winston-Salem, NC, United States.
⁵ Department of Medicine (Pulmonology and Critical Care), Wake Forest School of Medicine, Winston-Salem, NC, United States.
⁶ Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, NC, United States.
⁷ Department of Radiology, Wake Forest School of Medicine, Winston-Salem, NC, United States.
⁸ Department of Medicine (Hematology & Oncology), Wake Forest School of Medicine, Winston-Salem, NC, United States.
⁹ W.G. (Bill) Hefner Veteran Administration Medical Center, Cancer Center, Salisbury, NC, United States.

Abstract

The Comprehensive, Computable NanoString Diagnostic gene panel (C2Dx) is a promising solution to address the need for a molecular pathological research and diagnostic tool for precision oncology utilizing small volume tumor specimens. We translate subtyping-related gene expression patterns of Non-Small Cell Lung Cancer (NSCLC) derived from public transcriptomic data which establish a highly robust and accurate subtyping system. The C2Dx demonstrates supreme performance on the NanoString platform using microgram-level FNA samples and has excellent portability to frozen tissues and RNA-Seq transcriptomic data. This workflow shows great potential for research and the clinical practice of cancer molecular diagnosis.

Keywords: cancer subtyping; elastic net regularization; fine needle aspiration; logistic regression; molecular signature; non-small cell lung cancer.