Identification of Two Subgroups of FOLFOX Resistance Patterns and Prediction of FOLFOX Response in Colorectal Cancer Patients

Abstract

To dissect gene expression subgroups of FOLFOX resistance colorectal cancer(CRC) and predict FOLFOX response, gene expression data of 83 stage IV CRC tumor samples (FOLFOX responder n = 42, non-responder n = 41) are used to develop a novel iterative supervised learning method IML. IML identified two mutually exclusive subgroups of CRC patients that rely on different DNA damage repair proteins and resist FOLFOX. IML was validated in two validation sets (HR = 2.6, p Value = 0.02; HR = 2.36, p value = 0.02). A subgroup of mesenchymal subtype patients benefit from FOLFOX. Different subgroups of FOLFOX nonresponders may need to be treated differently.

Keywords:

• Colorectal cancer
• biomarker
• FOLFOX response
• prediction method

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Acknowledgements

The authors thank Wu Rujia for project planning and sample statistics. This manuscript has been released as a pre-print at: https://doi.org/10.1101/2020.06.10.20127167.

Ethics approval and consent to participate

No human or animal ethics approval was required for this study.

Author contributions

Design and concept: ST and GC. Sample collection and data quality: FW, SL. Data analysis and statistics: ST. Write the first draft: ST. Read and review the final paper: ST, FW, SL and GC.

Disclosure statement

Employment and stocks of Carbon Logic Biotech: ST. Inventor of a patent application: ST and GC. All remaining authors have declared no conflicts of interest.

Data availability statement

Data generated for the current study are available from the corresponding author on reasonable request.