Miseker Abate1,2,3, Elvira Vos1, Mithat Gonen4, Yelena Y Janjigian5, Mark Schattner6, Monika Laszkowska7, Laura Tang6, Steven B Maron5, Daniel G Coit1, Santosh Vardhana2, Chad Vanderbilt6, Vivian E Strong1. 1. Gastric and Mixed Tumor Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY. 2. Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY. 3. Department of Surgery, Weill Cornell Medicine, New York Presbyterian Hospital, New York, NY. 4. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY. 5. Gastrointestinal Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY. 6. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY. 7. Gastroenterology, Hepatology, and Nutrition Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
Abstract
OBJECTIVE: The microbiome is hypothesized to have a significant impact on cancer development. In gastric cancer (GC), Helicobacter pylori is an established class I carcinogen. However, additional organisms in the intratumoral microbiome play an important role in GC pathogenesis and progression. In this study, we characterize the full spectrum of the microbes present within GC and identify distinctions among molecular subtypes. METHODS: A microbiome bioinformatics pipeline that is generalizable across multiple next-generation sequencing platforms was developed. Microbial profiles for alpha diversity and enrichment were generated for 2 large, demographically distinct cohorts: (1) internal Memorial Sloan Kettering Cancer Center (MSKCC) and (2) The Cancer Genome Atlas (TCGA) cohorts. A total of 520 GC samples were compared with select tumor-adjacent nonmalignant samples. Microbiome differences among the GC molecular subtypes were identified. RESULTS: Compared with nonmalignant samples, GC had significantly decreased microbial diversity in both MSKCC and TCGA cohorts ( P <0.05). Helicobacter , Lactobacillus , Streptococcus , Prevotella , and Bacteroides were significantly more enriched in GC samples when compared with nonmalignant tissue ( P <0.05). Microsatellite instability-high GC had distinct microbial enrichment compared with other GC molecular subtypes. CONCLUSION: Distinct patterns of microbial diversity and species enrichment were identified in patients with GC. Given the varied spectrum of disease progression and treatment response of GC, understanding unique microbial signatures will provide the landscape to explore key microbial targets for therapy.
OBJECTIVE: The microbiome is hypothesized to have a significant impact on cancer development. In gastric cancer (GC), Helicobacter pylori is an established class I carcinogen. However, additional organisms in the intratumoral microbiome play an important role in GC pathogenesis and progression. In this study, we characterize the full spectrum of the microbes present within GC and identify distinctions among molecular subtypes. METHODS: A microbiome bioinformatics pipeline that is generalizable across multiple next-generation sequencing platforms was developed. Microbial profiles for alpha diversity and enrichment were generated for 2 large, demographically distinct cohorts: (1) internal Memorial Sloan Kettering Cancer Center (MSKCC) and (2) The Cancer Genome Atlas (TCGA) cohorts. A total of 520 GC samples were compared with select tumor-adjacent nonmalignant samples. Microbiome differences among the GC molecular subtypes were identified. RESULTS: Compared with nonmalignant samples, GC had significantly decreased microbial diversity in both MSKCC and TCGA cohorts ( P <0.05). Helicobacter , Lactobacillus , Streptococcus , Prevotella , and Bacteroides were significantly more enriched in GC samples when compared with nonmalignant tissue ( P <0.05). Microsatellite instability-high GC had distinct microbial enrichment compared with other GC molecular subtypes. CONCLUSION: Distinct patterns of microbial diversity and species enrichment were identified in patients with GC. Given the varied spectrum of disease progression and treatment response of GC, understanding unique microbial signatures will provide the landscape to explore key microbial targets for therapy.
Authors: Beth A Helmink; M A Wadud Khan; Amanda Hermann; Vancheswaran Gopalakrishnan; Jennifer A Wargo Journal: Nat Med Date: 2019-03-06 Impact factor: 53.440
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