한빛사논문
- 조회1,205
Intae Moon1,2, Jaclyn LoPiccolo3, Sylvan C. Baca3,4, Lynette M. Sholl5, Kenneth L. Kehl2, Michael J. Hassett2, David Liu2,3,6, Deborah Schrag7 & Alexander Gusev2,6,8,*
1Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, USA.
2Division of Population Sciences, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
3Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
4Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA.
5Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA.
6The Broad Institute of MIT & Harvard, Cambridge, MA, USA.
7Memorial Sloan Kettering Cancer Center, New York City, NY, USA.
8Division of Genetics, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA.
*Corresponding author: correspondence to Alexander Gusev
Abstract
Cancer of unknown primary (CUP) is a type of cancer that cannot be traced back to its primary site and accounts for 3–5% of all cancers. Established targeted therapies are lacking for CUP, leading to generally poor outcomes. We developed OncoNPC, a machine-learning classifier trained on targeted next-generation sequencing (NGS) data from 36,445 tumors across 22 cancer types from three institutions. Oncology NGS-based primary cancer-type classifier (OncoNPC) achieved a weighted F1 score of 0.942 for high confidence predictions (≥0.9) on held-out tumor samples, which made up 65.2% of all the held-out samples. When applied to 971 CUP tumors collected at the Dana-Farber Cancer Institute, OncoNPC predicted primary cancer types with high confidence in 41.2% of the tumors. OncoNPC also identified CUP subgroups with significantly higher polygenic germline risk for the predicted cancer types and with significantly different survival outcomes. Notably, patients with CUP who received first palliative intent treatments concordant with their OncoNPC-predicted cancers had significantly better outcomes (hazard ratio (HR) = 0.348; 95% confidence interval (CI) = 0.210–0.570; P = 2.32×10−5). Furthermore, OncoNPC enabled a 2.2-fold increase in patients with CUP who could have received genomically guided therapies. OncoNPC thus provides evidence of distinct CUP subgroups and offers the potential for clinical decision support for managing patients with CUP.
논문정보
- Research article
- 2023년 08월 (BRIC 등록일 2023-08-25)
- 국외 연구진
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