IMPORTANCE COVID-19 has disproportionately affected racial and ethnic minority groups, and race and ethnicity have been associated with disease severity. However, the association of socioeconomic determinants with racial disparities in COVID-19 outcomes remains unclear.OBJECTIVE To evaluate the association of race and ethnicity with COVID-19 outcomes and to examine the association between race, ethnicity, COVID-19 outcomes, and socioeconomic determinants.

Graphical abstract

Tobacco is the primary etiologic agent in worsened lung squamous cell carcinoma (LUSC) outcomes. Meanwhile, it has been shown that etiologic agents alter enhancer RNAs (eRNAs) expression. Therefore, we aimed to identify the effects of tobacco and electronic cigarette (e-cigarette) use on eRNA expression in relation to LUSC outcomes. We extracted eRNA counts from RNA-sequencing data of tumor/adjacent normal tissue and before/after e-cigarette tissue from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO), respectively. Tobacco-mediated LUSC eRNAs were correlated to patient survival, clinical variables, and immune-associated elements. eRNA expression was also correlated to mutation rates through the Repeated Evaluation of Variables Conditional Entropy and Redundance (REVEALER) algorithm and methylated sites through methylationArrayAnalysis. Differential expression analysis was then completed for the e-cigarette data to compare with key tobacco-mediated eRNAs. We identified 684 downregulated eRNAs and 819 upregulated eRNAs associated with tobacco-mediated LUSC, specifically, with the cancer pathological stage. We also observed a decrease in immune cell abundance in tobacco-mediated LUSC. Yet, we found an increased association of eRNA expression with immune cell abundance in tobacco-mediated LUSC. We identified 16 key eRNAs with significant correlations to 8 clinical variables, implicating these eRNAs in LUSC malignancy. Furthermore, we observed that these 16 eRNAs were highly associated with chromosomal alterations and reduced CpG site methylation. Finally, we observed large eRNA expression upregulation with e-cigarette use, which corresponded to the upregulation of the 16 key eRNAs. Our findings provide a novel mechanism by which tobacco and e-cigarette smoke influences eRNA interactions to promote LUSC pathogenesis and provide insight regarding disease progression at a molecular level.

Head and neck squamous cell carcinoma (HNSCC) tumor phenotypes and clinical outcomes are significantly influenced by etiological agents, such as HPV infection, smoking, and alcohol consumption. Accordingly, the intratumor microbiome has been increasingly implicated in cancer progression and metastasis. However, few studies characterize the intratumor microbial landscape of HNSCC with respect to these etiological agents. In this study, we aimed to investigate the bacterial and fungal landscape of HNSCC in association with HPV infection, smoking, and alcohol consumption. RNA-sequencing data were extracted from The Cancer Genome Atlas (TCGA) regarding 449 tissue samples and 44 normal samples. Pathoscope 2.0 was used to extract the microbial reads. Microbe abundance was compared to clinical variables, oncogenic signatures, and immune-associated pathways. Our results demonstrated that a similar number of dysregulated microbes was overabundant in smokers and nonsmokers, while heavy drinkers were characterized by an underabundance of dysregulated microbes. Conversely, the majority of dysregulated microbes were overabundant in HPV+ tumor samples when compared to HPV- tumor samples. Moreover, we observed that many dysregulated microbes were associated with oncogenic and metastatic pathways, suggesting their roles in influencing carcinogenesis. These microbes provide insights regarding potential mechanisms for tumor pathogenesis and progression with respect to the three etiological agents.

Background: Papillary thyroid carcinoma (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. Additionally, tall cell and poorly differentiated variants are more aggressive than classical and follicular variants of PTC. While the intratumor microbiome has become increasingly implicated in cancer development, the microbial landscape of PTC is essentially uninvestigated. Past studies have shown how microbes within tumor tissue can contribute to or inhibit tumor growth by regulating gene expression and immune and cancer pathways. For example, a study published by Bahmani S. et. al. found that the absence of folate-producing Bifidobacterium and Lactobacillus was correlated with hypomethylation at regions of the p53 gene in colorectal cancer. We hypothesized that intratumor microbiome composition distinctly alters the immune landscape by preventing or inducing methylation of critical genes and may therefore predict cancer progression between PTC subtypes and between patient genders. Methods: Raw whole-transcriptome RNA-sequencing data for PTC and adjacent normal tissue was downloaded from The Cancer Genome Atlas, and microbial reads were extracted using Pathoscope 2.0 software. The Kruskal-Wallis test was performed to identify differentially abundant microbes between tumor and normal samples. Level 3 normalized DNA methylation 450k sequencing was downloaded from the GDC portal. We converted B-values to M-values and then performed the probe-wise differential methylation analysis on the matrix of M-values in limma to obtain t-statistics and p-values for each CpG site. The Kruskal-Wallis test was used to correlate microbe abundance to extent of methylation. R Results: Overall, PTC tumor tissue significantly lacked microbes that are populated in adjacent normal tissue. Tissue from different genders and subtypes was characterized by dysbiosis of specific microbe species, and microbes distinctly abundant in tall cell and male patient cohorts were correlated with greater methylation of tumor suppressors. The most significantly methylated sites occurred on chromosomes 1 and 17 and specifically at cell cycle related genes. Lower microbe abundance (Anabaena sp. K119, Trueperella pyogenes, Frankia sp.) in tumor tissue was predominantly correlated with greater extent of methylation at known tumor suppressor genes including NEURL1B, POLE, and SRCIN1. Conclusions: We identified microbes that are uniquely abundant in specific PTC types and are predominantly negatively correlated with methylation of tumor suppressors and cell cycle-related genes. Our results may provide a basis for developing specialized prebiotic and probiotic treatments for varied PTC tumors. Citation Format: Aditi Gnanasekar, Grant Castaneda, Anjali Iyangar, Shruti Magesh, Jaideep Chakladar, Wei T. Li, Lindsay M. Wong, Weg M. Ongkeko. Absence of intratumor microbes induces methylation of tumor suppressors and cell cycle-related genes in papillary thyroid carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1784.

Lung squamous cell carcinoma (LUSC) is a highly heterogeneous cancer that is influenced by etiological agents such as tobacco smoke. Accordingly, transfer RNA-derived fragments (tRFs) are implicated in both cancer onset and development and demonstrate the potential to act as targets for cancer treatments and therapies. Therefore, we aimed to characterize tRF expression with respect to LUSC pathogenesis and clinical outcomes. Specifically, we analyzed the effect of tobacco smoke on tRF expression. In order to do so, we extracted tRF read counts from MINTbase v2.0 for 425 primary tumor samples and 36 adjacent normal samples. We analyzed the data in three primary cohorts: (1) all primary tumor samples (425 samples), (2) smoking-induced LUSC primary tumor samples (134 samples), and (3) non-smoking-induced LUSC primary tumor samples (18 samples). Differential expression analysis was performed to examine tRF expression in each of the three cohorts. tRF expression was correlated to clinical variables and patient survival outcomes. We identified unique tRFs in primary tumor samples, smoking-induced LUSC primary tumor samples, and non-smoking-induced LUSC primary tumor samples. In addition, many of these tRFs demonstrated correlations to worse patient survival outcomes. Notably, tRFs in the smoking-induced LUSC and non-smoking-induced LUSC primary tumor cohorts were significantly correlated to clinical variables pertaining to cancer stage and treatment efficacy. We hope that our results will be used to better inform future LUSC diagnostic and therapeutic modalities.