Multigene Expression Biomarkers and Score Systems for Predicting Therapeutic Benefit in Gastrointestinal Cancers

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Bo Hang, MD, PHD
Pin Wang, MD, PHD
Jian-Hua Mao, PHD


Gastrointestinal cancer is a leading cause of death among cancer patients worldwide. For both gastric and colorectal cancers, the 5-year overall survival for advanced stages remains low. Their polygenic and heterogeneous nature is characterized by alterations in multiple molecular pathways throughout its development, which is a big challenge for patient risk stratification and for treatment options. In this chapter, we describe the development of prognostic and predictive multigene signatures in gastrointestinal cancer patients for clinical use. We identified and validated a novel 53‐gene prognostic signature and score system that robustly and reliably predicts overall survival in gastric cancer patients. We also discovered that the predictive potential of the 53-gene signature that can identify gastric cancer patients who may benefit from adjuvant FOLFOX chemotherapy. In addition, we developed a 15-gene signature with robust prognostic function in colorectal cancers. Both signatures are independent of molecular subtypes and clinical outcomes. The predicting capability of these signatures supersedes previously published prognostic signatures in the same types of cancers. For clinical application, we developed a nucleic acid hybridization-based gene expression assay for the signatures. Future prospective studies are warranted to test the clinical value of these multigene signatures and fully deploy them into patient use.


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Chapter 6