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.
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.
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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 microbesprovide a basis for developing specialized prebiotic and probiotic treatments for varied PTC tumors.
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.
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.
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.
A systematic search of PubMed, medRxiv, bioRxiv, Embase, and the World Health Organization COVID-19 databases was performed for studies published from January 1, 2020, to January 6, 2021.
Studies that reported data on associations between race and ethnicity and COVID-19 positivity, disease severity, and socioeconomic status were included and screened by 2 independent reviewers. Studies that did not have a satisfactory quality score were excluded. Overall, less than 1% (0.47%) of initially identified studies met selection criteria.
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Associations were assessed using adjusted and unadjusted risk ratios (RRs) and odds ratios (ORs), combined prevalence, and metaregression. Data were pooled using a random-effects model.
The main measures were RRs, ORs, and combined prevalence values.
A total of 4 318 929 patients from 68 studies were included in this meta-analysis. Overall, 370 933 patients (8.6%) were African American, 9082 (0.2%) were American Indian or Alaska Native, 101 793 (2.4%) were Asian American, 851 392 identified as Hispanic/Latino (19.7%), 7417 (0.2%) were Pacific Islander, 1 037 996 (24.0%) were White, and 269 040 (6.2%) identified as multiracial and another race or ethnicity. In age- and sex-adjusted analyses, African American individuals (RR, 3.54; 95% CI, 1.38-9.07; P = .008) and Hispanic individuals (RR, 4.68; 95% CI, 1.28-17.20; P = .02) were the most likely to test positive for COVID-19. Asian American individuals had the highest risk of intensive care unit admission (RR, 1.93; 95% CI, 1.60-2.34, P < .001). The area deprivation index was positively correlated with mortality rates in Asian American and Hispanic individuals (P < .001). Decreased access to clinical care was positively correlated with COVID-19 positivity in Hispanic individuals (P < .001) and African American individuals (P < .001).
In this study, members of racial and ethnic minority groups had higher risks of COVID-19 positivity and disease severity. Furthermore, socioeconomic determinants were strongly associated with COVID-19 outcomes in racial and ethnic minority populations.
Abstract
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.
Head and Neck Squamous Cell Carcinoma (HNSCC) is a highly heterogeneous cancer that is characterized by distinct phenotypes based on anatomical site and etiological agents. Recently, the intratumor ...microbiome has been implicated in cancer pathogenesis and progression. Although it is well established that the gut microbiome varies with geographical location and is highly influenced by factors such as diet, environment, and genetics, the intratumor microbiome is not very well characterized. In this review, we aim to characterize the HNSCC intratumor microbiome by geographical location and anatomical site. We conducted a review of primary literature from PubMed and assessed studies based on relevancy and recency. To the best of our knowledge, we are the first to comprehensively examine the tumor microenvironment of HNSCC with respect to these two primary factors on a large scale. Our results suggest that there are unique bacterial and fungal biomarkers for HNSCC for each of the following geographical locations: North America, Asia, Europe, Australia, and Africa. We also identified a panel of microbial biomarkers that are unique to two primary HNSCC anatomic sites, as well as microbial biomarkers associated with various etiological agents of HNSCC. Future study of these microbes may improve HNSCC diagnostic and therapeutic modalities by accounting for differences based on geographic regions and anatomical sites.
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