Intratumoral Bacteria Dysbiosis Is Associated with Human Papillary Thyroid Cancer and Correlated with Oncogenic Signaling Pathways
Shuang Yu,
Yanqiang Ding,
Xuejie Wang,
Siu Kin Ng,
Siting Cao,
Weixin Liu,
Zhuming Guo,
Yubin Xie,
Shubin Hong,
Lixia Xu,
Xiaoxing Li,
Jie Li,
Weiming Lv,
Sui Peng,
Yanbing Li,
Joseph J.Y. Sung,
Jun Yu,
Haipeng Xiao
Affiliations
Shuang Yu
Department of Endocrinology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China
Yanqiang Ding
Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong 999077, China
Xuejie Wang
Department of Endocrinology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China
Siu Kin Ng
Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong 999077, China
Siting Cao
Department of Endocrinology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China
Weixin Liu
Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong 999077, China
Zhuming Guo
Department of Head and Neck Surgery, Sun Yat-Sen University Cancer Center, Guangzhou 510060, China
Yubin Xie
Clinical Trials Unit, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China
Shubin Hong
Department of Endocrinology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China
Lixia Xu
Institute of Precision Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China; Department of Oncology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China
Xiaoxing Li
Institute of Precision Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China
Jie Li
Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China
Weiming Lv
Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China
Sui Peng
Clinical Trials Unit, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China; Institute of Precision Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China
Yanbing Li
Department of Endocrinology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China
Joseph J.Y. Sung
Institute of Precision Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China; Lee Kong Chian School of Medicine, Nanyang Technology University, Singapore 308232, Singapore
Jun Yu
Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong 999077, China; Institute of Precision Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China; Corresponding authors.
Haipeng Xiao
Department of Endocrinology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China; Corresponding authors.
Emerging evidence suggests that microbial dysbiosis plays vital roles in many human cancers. However, knowledge of whether the microbial community in thyroid tumor is related to tumorigenesis remains elusive. In this study, we aimed to explore the microbial community in thyroid tissues and its contribution to papillary thyroid cancer (PTC). In parallel, we performed microbial profiling and transcriptome sequencing in the tumor and adjacent normal tissues of a large cohort of 340 PTC and benign thyroid nodule (BTN) patients. Distinct microbial signatures were identified in PTC, BTN, and their adjacent non-tumor tissues. Intra-thyroid tissue bacteria were verified by means of bacteria staining, fluorescence in situ hybridization, and immunoelectron microscopy. We found that 17 bacterial taxa were differentially abundant in PTC compared with BTN, which included enrichment in PTC of the pathobionts Rhodococcus, Neisseria, Streptococcus, Halomonas, and Devosia, and depletion of the beneficial bacteria Amycolatopsis. These differentially abundant bacteria could differentiate PTC tumor tissues (PTC-T) from BTN tissues (BTN-T) with an area under the curve (AUC) of 81.66%. Microbial network analysis showed increased correlation strengths among the bacterial taxa in PTC-T in comparison with BTN-T. Immune-function-corresponding bacteria (i.e., Erwinia, Bacillus, and Acinetobacter) were found to be enriched in PTC with Hashimoto’s thyroiditis. Moreover, our integrative analysis revealed that the PTC-enriched bacteria had a positive association with key PTC-oncogenic pathway-related genes, including BRAF, KRAS, IRAK4, CTNNB1, PIK3CA, MAP3K7, and EGFR. In conclusion, our results suggest that intratumor bacteria dysbiosis is associated with the thyroid tumorigenesis and oncogenic signaling pathways of PTC.
