The intratumor microbiome predicts prognosis across gender and subtypes in papillary thyroid carcinoma

Aditi Gnanasekar; Grant Castaneda; Anjali Iyangar; Shruti Magesh; Daisy Perez; Jaideep Chakladar; Wei Tse Li; Michael Bouvet; Eric Y Chang; Weg M Ongkeko

doi:10.1016/j.csbj.2021.03.032

The intratumor microbiome predicts prognosis across gender and subtypes in papillary thyroid carcinoma

Comput Struct Biotechnol J. 2021 Apr 9:19:1986-1997. doi: 10.1016/j.csbj.2021.03.032. eCollection 2021.

Authors

Aditi Gnanasekar^{1

2}, Grant Castaneda^{1

2}, Anjali Iyangar^{1

2}, Shruti Magesh^{1

2}, Daisy Perez^{1

3}, Jaideep Chakladar^{1

2}, Wei Tse Li^{1

2}, Michael Bouvet^{4

3

5}, Eric Y Chang^{6

7}, Weg M Ongkeko^{1

2}

Affiliations

¹ Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, UC San Diego School of Medicine, San Diego, CA 92093, USA.
² Research Service, VA San Diego Healthcare System, San Diego, CA 92161, USA.
³ Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
⁴ Department of Surgery, UC San Diego School of Medicine, San Diego, CA 92093, USA.
⁵ Surgery Service, VA San Diego Healthcare System, San Diego, CA 92161, USA.
⁶ Department of Radiology, University of California, San Diego, CA CA 92093, USA.
⁷ Radiology Service, VA San Diego Healthcare System, San Diego, 92161, USA.

Abstract

While the intratumor microbiome has become increasingly implicated in cancer development, the microbial landscape of papillary thyroid carcinoma (PTC) is essentially uninvestigated. PTC is characterized by varied prognosis between gender and cancer subtype, but the cause for gender and subtype-based dissimilarities is unclear. Women are more frequently diagnosed with PTC, while men suffer more advanced-staged PTC. In addition, tall cell variants are more aggressive than classical and follicular variants of PTC. We hypothesized that intratumor microbiome composition distinctly alters the immune landscape and predicts clinical outcome between PTC subtypes and between patient genders. Raw whole-transcriptome RNA-sequencing, Level 3 normalized mRNA expression read counts, and DNA methylation 450 k sequencing data for untreated, nonirradiated tumor, and adjacent normal tissue were downloaded from the Genomic Data Commons (GDC) legacy archive for 563 thyroid carcinoma patients. Microbe counts were extracted using Pathoscope 2.0 software. We correlated microbe abundance to clinical variables and immune-associated gene expression. Gene-set enrichment, mutation, and methylation analyses were conducted to correlate microbe abundance to characterize microbes' roles. Overall, PTC tumor tissue significantly lacked microbes that are populated in adjacent normal tissue, which suggests presence of microbes may be critical in controlling immune cell expression and regulating immune and cancer pathways to mitigate cancer growth. In contrast, we also found that microbes distinctly abundant in tall cell and male patient cohorts were also correlated with higher mutation expression and methylation of tumor suppressors. Microbe dysbiosis in specific PTC types may explain observable differences in PTC progression and pathogenesis. These microbes provide a basis for developing specialized prebiotic and probiotic treatments for varied PTC tumors.

Keywords: Gender; Microbiome; Papillary thyroid carcinoma; Subtype.