Abstract
Current drug development efforts on gastric cancer are directed against several molecular targets driving the growth of this neoplasm. Intra-tumoral biomarker heterogeneity however, commonly observed in gastric cancer, could lead to biased selection of patients. MET, ATM, FGFR2, and HER2 were profiled on gastric cancer biopsy samples. An innovative pathological assessment was performed through scoring of individual biopsies against whole biopsies from a single patient to enable heterogeneity evaluation. Following this, false negative risks for each biomarker were estimated in silico. 166 gastric cancer cases with multiple biopsies from single patients were collected from Shanghai Renji Hospital. Following pre-set criteria, 56 ~ 78% cases showed low, 15 ~ 35% showed medium and 0 ~ 11% showed high heterogeneity within the biomarkers profiled. If 3 biopsies were collected from a single patient, the false negative risk for detection of the biomarkers was close to 5% (exception for FGFR2: 12.2%). When 6 biopsies were collected, the false negative risk approached 0%. Our study demonstrates the benefit of multiple biopsy sampling when considering personalized healthcare biomarker strategy, and provides an example to address the challenge of intra-tumoral biomarker heterogeneity using alternative pathological assessment and statistical methods.
Highlights
Gastric cancer (GC) is one of the most common cancers worldwide, with around half of all cases occurring in Eastern Asia, and is the third leading cause of cancer-related death worldwide [1]
Intra-tumoral biomarker heterogeneity has long been an issue in the selection of patients for clinical trials and understanding tumor heterogeneity is crucial to the successful deployment of a personalized healthcare biomarker (PHB) strategy
Our results showed that high levels of heterogeneity were only found in 0 ~ 11% of the positive cases, while most positive cases (56% ~ 78%) showed low heterogeneity, indicating a relatively low level of heterogeneity for our selected biomarkers in this cohort of GC cases
Summary
Gastric cancer (GC) is one of the most common cancers worldwide, with around half of all cases occurring in Eastern Asia (mainly China), and is the third leading cause of cancer-related death worldwide [1]. The incidence is decreasing, most GC cases are diagnosed at an PLOS ONE | DOI:10.1371/journal.pone.0143207. Intra-Tumoral Heterogeneity in Gastric Cancer stakeholders of AstraZeneca. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials. The authors declare that they have no other competing interests
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