In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. 11541-11541
Abstract:
11541 Background: Sarcoma is a heterogeneous group of malignant tumors that consist of distinct histological and molecular subtypes, each with unique features. Despite immunotherapy’s promise in many cancers, immunotherapeutic approaches for sarcoma have had variable response rates. Evaluating the tumor microbiome is a promising new approach that aims to improve our understanding of the immunogenicity of sarcoma subtypes, leading to improved treatment options and better clinical outcomes. Methods: We utilized The Cancer Genome Atlas (TCGA) and Genome Tissue Expression (GTEx) database to obtain RNA sequencing (RNAseq) data to identify microbes in sarcoma samples (all subtypes available). Due to the large number of sarcoma subtypes, we focused on three groups: dedifferentiated liposarcoma (DDLPS), leiomyosarcoma (LMS) and “other,” representing all other sarcoma subtypes. We utilized ExoTIC, “Exogenous sequences in Tumors and Immune cells,” a tool recently developed by Dr. Daniel Spakowicz and Dr. Xaiokui Mo. ExoTIC takes raw RNAseq reads and carefully aligns to both human and non-human reference genomes to identify low-abundance microbes. Models of association were analyzed based on each of the three groups as well as all the samples: “All” group. We performed Cox proportional hazards regression to identify the microbes associated with overall survival (OS). Results: We evaluated 97 LMS, 56 DDLPS and 100 “other” RNAseq samples (Table). ExoTIC identified 1304 microbes, of which 431 were statistically associated with OS in the “All” group. Of these, 50 microbes were statistically associated only with DDLPS, 54 only with LMS (e.g., Candida dubliniensis, Mycobacterium avium, Streptococcus sp. Z15), and 46 with “other.” The presence of no organism was associated with improved survival. Median hazard ratios were largest in DDLPS (2.3), followed by “other” (2.1) and LMS (1.9). Only 18 microbes were found in the DDLPS, LMS and “All” groups, including Bacillus sp., Streptococcus lutetiensis, Clostridium tetani, and Pseudomonas sp. LTJR-52. Each was negatively correlated with survival with a median hazard ratio of 2.5. Conclusions: We found a specific relationship between microbial presence and histological sarcoma subtype (DDLPS, LMS), which also statistically correlated with OS. Assessing individual characteristics of a sarcoma histological subtype with its particular microenvironment (e.g., microbes) can lead to personalized treatment insights and improvements in outcomes. Our future research will consist of validating and correlation of the microbial profile of sarcoma subtypes with clinical outcomes retrospectively and prospectively. [Table: see text]
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2021.39.15_suppl.11541
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2021
detail.hit.zdb_id:
2005181-5
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