Abstract 6095: Unique tumor microbiome in microsatellite instability high (MSI-H) colon carcinoma
Authors: Vanderbilt Chad Michael , Keshinro Ajaratu , Chen Chin-Tung , Babady Esther , Berger Michael F. , Zehir Ahmet , Ladanyi Marc , Hechtman Jaclyn F. , Stadler Zsofia K. , Shia Jinru , Weiser Martin R. 
Published: September 2020

Abstract
The study was undertaken to determine if microsatellite instability (MSI) status influences the composition of the tumor microbiome in primary colon carcinoma. 426 unique primary, stage I-III colon biopsy or resection specimens (234 right-sided, 192 left-sided) were sequenced by MSK-IMPACT, a large panel next generation sequencing (NGS) assay. MSI status [150 MSI-H; 276 microsatellite stable (MSS)] was determined using the MSISensor algorithm, which is clinically validated to detect MSI status from NGS data. We have developed a technique for identifying the presence of microbial species in tumor tissue being tested with NGS by analysis of non-human DNA read sequences. The method has been validated and determined to have comparable accuracy to reference microbial tests for both viruses and bacteria. We identified 13 bacterial species that are enriched in MSI-H colon carcinoma compared to MSS (odds ratio, 95% confidence interval greater than 1 with Bonferonni adjustment) (Table 1). We also observed that MSI-H is more common in right-sided tumors compared to left-sided tumors (53% vs. 13%, p=1.0E-4). To understand if sidedness of the tumor was a significant confounder, we performed stratified analysis of bacteria enrichment for right and left sided colon carcinoma. 8 of the 13 species remained significantly enriched in MSI-H tumors independent of sidedness; 9 of 13 in right-sided tumors; and 12 of 13 in left-sided tumors. Non-significant confidence intervals are underlined in Table 1. While Fusobacterium nucleatum has previously been reported to be enriched in MSI-H colon cancer, the broader spectrum of species enriched in MSI-H colon carcinoma we observed in our study has not been reported. The different microbiome suggests that either these bacteria play a role in development of MSI-H tumors or a unique immune environment exists in MSI-H tumors. The relationship between this unique microbiome and MSI status is the focus of further investigation.
Table 1:Bacteria enriched in MSI-H colon cancerMSI-HMSI-HMSI-HMSSMSSMSSBacteria speciesLocationPositiveNegativeTotalPositiveNegativeTotalOdds ratioBonferroni adjusted 95% confidence intervalFusobacterium nucleatumTotal/right/left54/44/1096/81/15150/125/2538/20/18238/89/149276/109/1673.5/2.4/5.5(1.6-7.7)/(1.3-4.4)/(2.2-14.1)Bacteroides fragilisTotal/right/left47/35/12103/90/13150/125/2537/16/21239/93/146276/109/1672.9/2.3/6.4(1.3-6.5)/(1.2-4.4)/(2.6-15.9)Prevotella intermediaTotal/right/left27/22/5123/103/20150/125/2514/10/4262/99/163276/109/1674.1/2.1/10.2(1.4-12.5)/(1.01-4.7)/(2.5-41.1)Prevotella melaninogenicaTotal/right/left20/18/2130/107/23150/125/256/3/3270/106/164276/109/1676.9/5.9/4.8(1.5-31.9)/(1.7-20.8)/(0.8-30.0)Odoribacter splanchnicusTotal/right/left26/20/6124/105/19150/125/2513/5/8263/104/159276/109/1674.2/4.0/6.3(1.4-13.3)/(1.4-11.0)/(2.0-20.0)Selenomonas sputigenaTotal/right/left33/31/2117/94/23150/125/2522/15/7254/94/160276/109/1673.3/2.1/2.0(1.3-8.4)/(1.04-4.1)/(0.4-10.2)Bacteroides xylanisolvensTotal/right/left32/25/7118/100/18150/125/2521/8/13255/101/154276/109/1673.3/3.2/4.6(1.3-8.6)/(1.4-7.3)/(1.6-13.0)Prevotella denticolaTotal/right/left20/16/4130/109/21150/125/259/3/6267/106/161276/109/1674.6/5.2/5.1(1.2-17.2)/(1.5-18.3)/(1.3-19.6)Leptotrichia buccalisTotal/right/left17/13/4133/112/21150/125/256/5/1270/104/166276/109/1675.8/2.4/31.6(1.2-27.2)/(0.8-7.0)/(3.4-296.4)Prevotella sp. oral taxon 299Total/right/left14/12/2136/113/23150/125/252/1/1274/108/166276/109/16714.1/11.5/14.4(1.2-161.7)/(1.5-89.7)/(1.3-165.6)Porphyromonas gingivalisTotal/right/left13/10/3137/115/22150/125/252/0/2274/109/165276/109/16713.0/19.9/11.3(1.1-150.8)/(1.1-343.0)/(1.8-71.1)Streptococcus anginosusTotal/right/left19/16/3131/109/22150/125/2510/4/6266/105/161276/109/1673.9/3.9/3.7(1.1-14.1)/(1.2-11.9)/(0.9-15.7)Fretibacterium fastidiosumTotal/right/left15/13/2135/112/23150/125/256/3/3270/106/164276/109/1675.0/4.1/4.8(1.03-24.3)/(1.1-14.8)/(0.8-30.0)
Citation Format: Chad Michael Vanderbilt, Ajaratu Keshinro, Chin-Tung Chen, Esther Babady, Michael F. Berger, Ahmet Zehir, Marc Ladanyi, Jaclyn F. Hechtman, Zsofia K. Stadler, Jinru Shia, Martin R. Weiser. Unique tumor microbiome in microsatellite instability high (MSI-H) colon carcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6095.