Naseem, Madiha; Cao, Shu; Yang, Dongyun; Millstein, Joshua; Puccini, Alberto; Loupakis, Fotios; Stintzing, Sebastian; Cremolini, Chiara; Tokunaga, Ryuma; Battaglin, Francesca; Soni, Shivani; Berger, Martin D.; Barzi, Afsaneh; Zhang, Wu; Falcone, Alfredo; Heinemann, Volker; Lenz, Heinz-Josef (2021). Random survival forests identify pathways with polymorphisms predictive of survival in KRAS mutant and KRAS wild-type metastatic colorectal cancer patients. Scientific reports, 11(1), p. 12191. Springer Nature 10.1038/s41598-021-91330-z
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KRAS status serves as a predictive biomarker of response to treatment in metastatic colorectal cancer (mCRC). We hypothesize that complex interactions between multiple pathways contribute to prognostic differences between KRAS wild-type and KRAS mutant patients with mCRC, and aim to identify polymorphisms predictive of clinical outcomes in this subpopulation. Most pathway association studies are limited in assessing gene-gene interactions and are restricted to an individual pathway. In this study, we use a random survival forests (RSF) method for identifying predictive markers of overall survival (OS) and progression-free survival (PFS) in mCRC patients treated with FOLFIRI/bevacizumab. A total of 486 mCRC patients treated with FOLFIRI/bevacizumab from two randomized phase III trials, TRIBE and FIRE-3, were included in the current study. Two RSF approaches were used, namely variable importance and minimal depth. We discovered that Wnt/β-catenin and tumor associated macrophage pathway SNPs are strong predictors of OS and PFS in mCRC patients treated with FOLFIRI/bevacizumab independent of KRAS status, whereas a SNP in the sex-differentiation pathway gene, DMRT1, is strongly predictive of OS and PFS in KRAS mutant mCRC patients. Our results highlight RSF as a useful method for identifying predictive SNPs in multiple pathways.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology |
UniBE Contributor: |
Berger, Martin Dave |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
2045-2322 |
Publisher: |
Springer Nature |
Language: |
English |
Submitter: |
Rebeka Gerber |
Date Deposited: |
29 Sep 2021 07:52 |
Last Modified: |
05 Dec 2022 15:53 |
Publisher DOI: |
10.1038/s41598-021-91330-z |
PubMed ID: |
34108518 |
BORIS DOI: |
10.48350/159246 |
URI: |
https://boris.unibe.ch/id/eprint/159246 |
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